Letter from Prof Rolf Stahel Dear Colleagues It is my pleasure to present this ETOP slide set which has been designed to highlight and summarise key findings in thoracic cancers from the major congresses in 2016. This slide set specifically focuses on the ESMO 2016 Congress and is available in 4 languages – English, French, Japanese and Chinese. The area of clinical research in oncology is a challenging and ever changing environment. Within this environment we all value access to scientific data and research which helps to educate and inspire further advancements in our roles as scientists, clinicians and educators. I hope you find this review of the latest developments in thoracic cancers of benefit to you in your practice. If you would like to share your thoughts with us we would welcome your comments. Please send any correspondence to etop@etop.eu-org. I would like to thank our ETOP members Drs Solange Peters and Martin Reck for their roles as Editors – for prioritising abstracts and reviewing slide content. The slide set you see before you would not be possible without their commitment and hard work. And finally, we are also very grateful to Lilly Oncology for their financial, administerial and logistical support in the realisation of this complex yet rewarding activity. Yours sincerely, Rolf Stahel President, ETOP Foundation Council

ETOP Medical Oncology Slide Deck Editors 2016 Focus: Advanced NSCLC (not radically treatable stage III & stage IV) and related biomarker data Dr Solange Peters Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland Focus: Early and locally advanced NSCLC (stage I–III) and related biomarker data / other malignancies Dr Martin Reck Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany

Contents Biomarkers and screening Early stage and locally advanced NSCLC – Stages I, II and III Advanced NSCLC – Not radically treatable stage III and stage IV 1st line Later lines Other malignancies SCLC and mesothelioma Rare tumours

Biomarkers and screening

1055O: Changes in serum IL8 levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small cell lung cancer patients – Sanmamed MF, et al Study objective To evaluate the use of serum IL-8 as a biomarker during anti-PD-1 mAb treatment of metastatic melanoma and NSCLC patients Methods Serum IL-8 levels were determined in 44 metastatic melanoma and 19 metastatic NSCLC patients undergoing anti-PD-1 mAb therapy Key results In responding NSCLC patients, compared with baseline levels (16.3 pg/mL), serum IL-8 levels decreased significantly at the moment of best response (6 pg/mL; p<0.05) and increased upon progression (53 pg/mL; NS) In non-responding NSCLC patients, IL-8 levels significantly increased at the moment of progression vs. baseline levels (51 vs. 12 pg/mL; p<0.05) Changes in serum IL-8 levels are associated with OS in NSCLC, change <9.2% vs. >9.2% HR 7.7 (95%CI 1.1, 55.8); p=0.004 Conclusions Changes in serum IL-8 levels reflect the response to anti-PD-1 mAbs in melanoma and NSCLC patients Early decrease in serum IL-8 levels is associated with longer survival in metastatic melanoma and NSCLC patients treated with anti-PD-1 mAbs Sanmamed et al. Ann Oncol 2016; 27 (suppl 6): abstr 1055O

1521PD: Clinical evaluation of the utility of a liquid biopsy (circulating tumoral cells and ctDNA) to determine the mutational profile (EGFR, KRAS, ALK, ROS1 and BRAF) in advanced NSCLC patients – Barrera L, et al Study objective To assess the utility of a liquid biopsy for mutation detection in advanced NSCLC Methods Patients with advanced NSCLC who had either a new diagnosis or developed resistance to an EGFR TKI were eligible for inclusion 62 patients were screened for EGFR, KRAS, ROS1, ALK and BRAF mutations via plasma genotyping (by the Target-SelectorTM ctDNA assay) and compared with tissue biopsies Key results The plasma assay showed a 90% (95%CI 82.83, 95.10) sensitivity for the detection of EGFR mutations and 100% (95%CI 96.38, 100) specificity Of those who were enrolled with EGFR TKI resistance (n=52), 57% of those with polymetastatic disease had a T790M mutation, while 16% of those with oligometastatic disease had a T790M mutation, and none with loco-regional disease Conclusion EGFR mutations can be rapidly detected with a noninvasive ctDNA assay; however, conclusions regarding other driver alterations will require additional data Barrera et al. Ann Oncol 2016; 27 (suppl 6): abstr 1521PD

1202O: Clinical and biological characteristics of non-small cell lung cancer (NSCLC) harbouring EGFR mutation: Results of the nationwide programme of the French Cooperative Thoracic Intergroup (IFCT) – Leduc C, et al Study objective To analyse the EGFR mutation status of patients with EGFR-mutated NSCLC Methods The Biomarkers France database (containing data on 17,664 patients at time of study) was used to identify patients with EGFR-mutated NSCLC Overall, 1837 (10.3%) patients were eligible for inclusion in this analysis Key results EGFR mutations were identified as follows: Exon 18: 102 (5.6%) patients Exon 19: 931 (50.6%) patients Exon 20: 102 (5.6%) patients Exon 21: 702 (38.2%) patients 70 of these mutations were novel There was a higher proportion of smokers displaying exon 18 (20%) or exon 20 (19%) mutations compared with exon 19 (11%) or exon 21 (11%) (p=0.002) In total, 226 patients had a personal history of cancer; this was not linked to exon mutation status Patients displaying a T790M mutation were excluded from the survival analysis Median follow-up time was 36.7 (36.4–37) months Leduc et al. Ann Oncol 2016; 27 (suppl 6): abstr 1202O

1202O: Clinical and biological characteristics of non-small cell lung cancer (NSCLC) harbouring EGFR mutation: Results of the nationwide programme of the French Cooperative Thoracic Intergroup (IFCT) – Leduc C, et al Key results (cont.) Median OS improved for exon 19 deletions vs. L858 mutations (26.5 vs. 21.3 months, p=0.045); deletion length had no impact on OS For exon 21, median OS was longer for L858R compared with L861Q, other substitutions or wild-type (22.4 vs. 14.1 vs. 14.9 vs. 11.8, respectively; p<0.0001) For mutations further classified as common, rare or complex, DCR was 82%, 77% and 54.5%, respectively, under first-line EGFR-TKI therapy (p=0.05) No difference in DCR under EGFR-TKI therapy was observed according to mutation type for exon 19 or 21 Conclusions Distinct clinical characteristics were observed for common and uncommon EGFR mutations Patients with common exon 19 mutations tended to have better outcomes Wild-type Exon 18 Exon 19 Exon 20 Exon 21 p-value OS, months [95%CI] 11.8 [10.1, 13.3] (n=1270) 14.2 [12.4, NR] (n=44) 27.0 [23.4, 29.1] (n=555) 16.0 [8.1, 19.1] (n=50) 21.3 [18.5, 27.8] (n=439) <0.001 PFS (first-line EGFR TKI), months [95%CI] 7.2 [6.3, 7.9] (n=1243) 12.4 [5.8, NR] (n=44) 16.3 [13.9, 18.0] (n=560) 6.4 [2.9, 9.0] (n=48) 13.7 [11.6, 16.1] (n=442) <0.0001 DCR (TKI), % 21 (n=14) 78 (n=9) 82 (n=235) 20 (n=5) 81 (n=201) Leduc et al. Ann Oncol 2016; 27 (suppl 6): abstr 1202O

Early and locally advanced NSCLC Stages I, II and III

Standard of care post-op treatment LBA41_PR: Neoadjuvant anti-PD1, nivolumab, in early stage resectable non-small-cell lung cancer – Forde RM, et al Study objective To assess neoadjuvant nivolumab in patients with early stage NSCLC Key patient inclusion criteria Newly diagnosed resectable stage I (>2 cm)/II/IIIA NSCLC (n=19) Nivolumab 3 mg/kg IV Days -28 and -14 with repeat CT prior to planned surgical resection on Day 0 Standard of care post-op treatment 30 days Primary endpoint Safety and feasibility Exploratory endpoints Pathologic regression, radiographic response Forde et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA41_PR

LBA41_PR: Neoadjuvant anti-PD1, nivolumab, in early stage resectable non-small-cell lung cancer – Forde RM, et al Key results The single grade 3–4 TRAE discontinuation was related to fever and lung tumour cavitation, the patient underwent an uncomplicated surgery and postoperative follow-up Treatment-related AEs Any grade Grade 3–4 Any treatment-related AE, % 32 5 Treatment-related AEs leading to discontinuation, % Treatment-related delays to surgery None Specific treatment-related AEs Grade 1–2 GI, % 21 Skin/musculoskeletal, % 11 Pulmonary, % Other, % Forde et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA41_PR

LBA41_PR: Neoadjuvant anti-PD1, nivolumab, in early stage resectable non-small-cell lung cancer – Forde RM, et al Key results (cont.) At resection, 7 (39 %) patients had <10% residual viable tumour cells (defined as major pathologic response); 1 patient had a pathological complete response Conclusions Nivolumab administered preoperatively in early stage NSCLC is well tolerated, and radiologic and/or pathologic regression was observed in several patients Many pathological responses were observed independently of radiological responses Radiographic response (n=18) Response, % Partial response 22 Stable disease 72 Progressive disease 6 Pathologic downstaging from pre-treatment clinical stage (n=17)* Yes 39 No 61 *Only resected patients included in analysis Forde et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA41_PR

1178O: Multi-centre randomized controlled study comparing adjuvant vs neo-adjuvant chemotherapy with docetaxel plus carboplatin in resectable stage IB to IIIA NSCLC: final results of CSLC0501 – Wu Y, et al Study objective To compare DFS between adjuvant and neoadjuvant chemotherapy in resectable NSCLC Key patient inclusion criteria Histologically/cytologically confirmed stage IB–IIIA NSCLC No prior chemotherapy, radiotherapy or target therapy ECOG PS 0–1 (n=198) Adjuvant: Docetaxel 75 mg/m2 + carboplatin AUC5 q3w (n=101) PD Stratification Gender Centre Stage (1B vs. II vs. IIIA) Pathology (adeno vs. non-adeno) R Neoadjuvant: Docetaxel 75 mg/m2 + carboplatin AUC5 q3w (n=97) PD Primary endpoint 3-year DFS Secondary endpoints 5-year OS, safety Wu et al. Ann Oncol 2016; 27 (suppl 6): abstr 1178O

In the neoadjuvant arm ORR was 34.4% and DCR was 34.4% 1178O: Multi-centre randomized controlled study comparing adjuvant vs neo-adjuvant chemotherapy with docetaxel plus carboplatin in resectable stage IB to IIIA NSCLC: final results of CSLC0501 – Wu Y, et al Key results Chemotherapy was completed in 100% of the neoadjuvant arm vs. 85.1% of the adjuvant arm, with a mean of 3 cycles for each There was no surgery in 15.5% of the neoadjuvant arm vs. 0% of the adjuvant arm In the neoadjuvant arm ORR was 34.4% and DCR was 34.4% Neoadjuvant Adjuvant HR (95%CI) p-value 3-year DFS, years, median (95%CI) 2.3 (1.6, 3.0) NR 0.73 (0.49, 1.09) 0.126 Total DFS, years, median (95%CI)* 5.2 (1.3, 9.0) 0.70 (0.49, 1.01) 0.057 5-year OS, years, median (95%CI) 4.2 (3.2, 5.2) 0.66 (0.44, 1.00) 0.050 Total OS, years, median (95%CI)* 7.3 0.71 (0.48, 1.05) 0.087 *The study was closed early due to slow accrual and the phase 1b proportion was stopped as adjuvant therapy was no longer feasible Wu et al. Ann Oncol 2016; 27 (suppl 6): abstr 1178O

1178O: Multi-centre randomized controlled study comparing adjuvant vs neo-adjuvant chemotherapy with docetaxel plus carboplatin in resectable stage IB to IIIA NSCLC: final results of CSLC0501 – Wu Y, et al Key results (cont.) Grade 3–4 events occurred in 45.4% and 35.6% of patients, respectively, in the neoadjuvant and adjuvant arms (p=0.21) The most common grade 3–4 event was granulocytopenia occurring in 41.2% (neoadjuvant) and 31.7% (adjuvant) of patients Conclusions Docetaxel + carboplatin is safe as either adjuvant or neoadjuvant chemotherapy in resectable clinical stage IB–IIIA NSCLC There was no statistically significant difference between the adjuvant and neoadjuvant arms in OS or 3-year DFS, with a trend in favour of adjuvant therapy for DFS and 5-year OS Wu et al. Ann Oncol 2016; 27 (suppl 6): abstr 1178O

Advanced NSCLC Not radically treatable stage III and stage IV 1st line

LBA43: Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7) – Paz-Ares L, et al Study objective A head-to-head trial of two EGFR-directed therapies, afatinib and gefitinib, as first-line therapy in EGFR+ NSCLC Key patient inclusion criteria Stage IIIB/IV lung adenocarcinoma EGFR mutation (Del19 and/or L858R) in the tumour tissue No prior treatment for advanced/metastatic disease ECOG PS 0/1 (n=319) Afatinib 40 mg/day (n=160) PD / toxicity Stratification Mutation type (Del19 vs. L858R) Brain metastases (present vs. absent) R 1:1 Gefitinib 250 mg/day (n=159) PD / toxicity Co-primary endpoints PFS (IR), TTF, OS Secondary endpoints ORR, TTR, DoR, tumour shrinkage, HRQoL Paz-Ares et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA43

LBA43: Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7) – Paz-Ares L, et al Key results Treatment discontinuation due to drug-related AEs was low in each arm (6%) Conclusions In patients with EGFR m+ NSCLC, afatinib significantly improved PFS, TTF and ORR compared with gefitinib, with no significant difference in OS AEs were tolerable and resulted in equally low rates of treatment discontinuation Afatinib (n=160) Gefitinib (n=159) HR (95%CI) p-value Median PFS (independent review), months 11.0 10.9 0.74 (0.57, 0.95) 0.0178 Median TTF, months 13.7 11.5 0.75 (0.60, 0.94) 0.0136 Median DoR, months 10.1 8.3 Median OS, months 27.9 24.5 0.86 (0.66, 1.12) 0.2580 Paz-Ares et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA43

Pembrolizumab + chemotherapy LBA46_PR: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-lie therapy for advanced NSCLC: KEYNOTE-021 cohort G – Langer C, et al Study objective To compare the efficacy and safety pembrolizumab + carboplatin and pemetrexed vs. carboplatin and pemetrexed alone as first-line therapy for patients with advanced nonsquamous NSCLC histology in KEYNOTE-021 Key patient inclusion criteria Untreated stage IIIB/IV nonsquamous NSCLC No EGFR mutation or ALK translocation Provision of sample for PD-L1 assessment ECOG PS 0–1 No untreated brain metastases (n=123) Pembrolizumab + chemotherapy Pembrolizumab 200 mg q3w (2 years) + carboplatin AUC5 mg/mL/min + pemetrexed 500 mg/m2 q3w (4 cycles)* (n=60) R 1:1 Stratification PD-L1 status (TPS ≥1 vs. <1%) Chemotherapy Carboplatin AUC5 mg/mL/min + pemetrexed 500 mg/m2 q3w (4 cycles)* (n=63) PD Pembro 200 mg q3w (2 years) Primary endpoint ORR (RECIST) Secondary endpoints PFS, OS, safety, relationship between anti-tumor activity and PD-L1 TPS *Pemetrexed 500 mg/m2 q3w permitted as maintenance therapy Langer et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA46_PR

Pembro + chemo responders (n=33) Chemo alone responders (n=18) LBA46_PR: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-lie therapy for advanced NSCLC: KEYNOTE-021 cohort G – Langer C, et al Key results Pembrolizumab + chemotherapy significantly improved the proportion of patients who achieved an ORR compared with chemotherapy alone Confirmed ORR ∆26% 100 p=0.0016 Pembro + chemo responders (n=33) Chemo alone responders (n=18) TTR, months median (range) 1.5 (1.2–12.3) 2.7 (1.1–4.7) DoR, months median (range) NR (1.4+–13.0+) NR (1.4+– 15.2+) Ongoing response, n (%) 29 (88) 14 (78) 80 55% 60 ORR, % (95%CI) 29% 40 20 Pembro + chemo Chemo alone Langer et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA46_PR

PFS (RECIST by Central Review) LBA46_PR: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-lie therapy for advanced NSCLC: KEYNOTE-021 cohort G – Langer C, et al Key results (cont.) PFS was significantly longer with pembrolizumab + chemotherapy compared with chemotherapy alone PFS, % 100 80 60 40 20 5 10 15 Time, months Pembro + chemo 23 33 Chemo alone Events, n HR (95%CI) 0.53 (0.31, 0.91) p=0.0102 Number at risk: 63 43 32 13 1 Median PFS, months PFS (RECIST by Central Review) 13.0 8.9 Langer et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA46_PR

LBA46_PR: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-lie therapy for advanced NSCLC: KEYNOTE-021 cohort G – Langer C, et al Key results (cont.) At data cut-off, there was no difference in OS between the treatment groups (p=0.39), with few events in either arm Events, n HR (95%CI) OS 100 Pembro + chemo 13 0.90 Chemo alone 14 (0.42, 1.91) 80 60 OS, % 40 20 5 10 15 20 Time, months Number at risk: 60 63 43 57 20 31 5 6 Langer et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA46_PR

Pembrolizumab + chemotherapy (n=59) LBA46_PR: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-lie therapy for advanced NSCLC: KEYNOTE-021 cohort G – Langer C, et al Key results (cont.) Exposure was 1.6 times longer in the pembrolizumab + chemotherapy group Most treatment-related AEs were mild and grade 1−2 severity Conclusions In chemotherapy-naïve advanced nonsquamous NSCLC, pembrolizumab + carboplatin and pemetrexed resulted in improved ORR and PFS vs. carboplatin and pemetrexed alone as first-line therapy Pembrolizumab + carboplatin and pemetrexed have a manageable safety profile OS data are awaited after a longer follow-up period Pembrolizumab + chemotherapy (n=59) Chemotherapy alone (n=62) Exposure, months median (range) 8.0 (1 d–16.1 mo) 4.9 (1 d–15.3 mo) Treatment-related AEs, n (%) Grade 3–4 Led to discontinuation Led to death 55 (93) 23 (39) 6 (10) 1 (2) 56 (90) 16 (26) 8 (13) 2 (3) Langer et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA46_PR

LBA8_PR: KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% – Reck M, et al Study objective To compare pembrolizumab vs. platinum-doublet chemotherapy as first-line therapy for advanced NSCLC of PD-L1 TPS ≥50% without treatable EGFR mutations or ALK translocations Pembrolizumab 200 mg q3w (2 years) (n=154) Key patient inclusion criteria Untreated stage IV NSCLC PD-L1 TPS ≥50% No activating EGFR mutation or ALK translocation No untreated brain metastases (n=305) PD / toxicity / other R Platinum-doublet chemotherapy* (n=151) PD / toxicity / other Primary endpoint PFS Secondary endpoints OS, ORR, safety *Carboplatin or cisplatin + pemetrexed, carboplatin or cisplatin + gemcitabine, or carboplatin + paclitaxel, with optional pemetrexed maintenance for nonsquamous NSCLC Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA8_PR

LBA8_PR: KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% – Reck M, et al Key results Pembrolizumab demonstrated superior PFS over chemotherapy in patients whose tumours express high levels of PD-L1 PFS Events, n Median, months HR (95%CI) p-value 100 Pembro 73 10.3 0.50 <0.001 80 Chemo 116 6.0 (0.37, 0.68) 60 PFS, % 40 20 3 6 9 12 15 18 Time, months Number at risk: 154 151 104 99 89 70 44 18 22 9 3 1 1 Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA8_PR

LBA8_PR: KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% – Reck M, et al Key results (cont.) Significant OS benefit was observed despite a 50% total crossover from chemotherapy to anti-PD-L1 therapy Events, n Median, months HR (95%CI) OS p-value Pembro 44 NR 0.60 100 0.005 Chemo 64 NR (0.41, 0.89) 80 60 OS, % 40 20 3 6 9 12 15 18 21 Time, months Number at risk: 154 151 136 123 121 106 82 64 39 34 11 7 2 1 Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA8_PR

Pembrolizumab responders (n=69) Chemotherapy responders (n=42) LBA8_PR: KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% – Reck M, et al Key results (cont.) There was an improvement in ORR with pembrolizumab over chemotherapy 6 CRs were observed with pembrolizumab Confirmed ORR ORR, % (95%CI) 60 40 20 Pembrolizumab Chemotherapy 45% 28% ∆17% p=0.0011 n=6 n=63 n=41 n=1 CR PR Pembrolizumab responders (n=69) Chemotherapy responders (n=42) TTR, months median (range) 2.2 (1.4−8.2) 2.2 (1.8–12.2) DoR, months median (range) NR (1.9+–14.5+) 6.3 (2.1+–12.6+) Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA8_PR

LBA8_PR: KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% – Reck M, et al Key results (cont.) Incidence of treatment-related AEs was lower with pembrolizumab compared with chemotherapy Conclusions Pembrolizumab demonstrated improved PFS, OS and ORR over chemotherapy, with a lower incidence of AEs PD-L1 TPS ≥50% is observed in ~1/3 of patients with advanced NSCLC and identifies those most likely to benefit from anti-PD-1 therapy Pembrolizumab (n=154) Chemotherapy (n=150) Exposure, months median (range) 7.0 (1 d–18.7 mo) 3.5 (1 d–16.8 mo) Treatment-related AEs, n (%) Grade 3–4 Serious Led to discontinuation Led to death 113 (73) 40 (26) 33 (21) 11 (7) 1 (<1) 135 (90) 77 (51) 31 (21) 16 (11) 3 (2) Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA8_PR

LBA7_PR: CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage IV/recurrent programmed death ligand 1 (PD-L1)–positive NSCLC – Socinski M, et al Study objective To evaluate the efficacy of first-line nivolumab vs. investigator choice of platinum-based doublet chemotherapy in stage IV/recurrent PD-L1-positive NSCLC Key patient inclusion criteria Stage IV or recurrent NSCLC No prior systemic therapy for advanced disease No EGFR/ALK mutations sensitive to targeted inhibitor therapy PD-L1 expression of ≥1% ECOG PS 0–1 (n=541) Nivolumab 3 mg/kg IV q2w (n=271) PD / toxicity Stratification PD-L1 expression (<5% vs. ≥5%) Histology (squamous vs. nonsquamous) R Nivolumab (optional) Chemotherapy* for 6 cycles (n=270) PD Primary endpoint PFS (≥5% PD-L1+) Secondary endpoints PFS (≥1% PD-L1+), OS, ORR *Investigator choice – histology dependent Socinski et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA7_PR

LBA7_PR: CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage IV/recurrent programmed death ligand 1 (PD-L1)–positive NSCLC – Socinski M, et al Key results PFS per IRRC in ≥5% PD-L1+ 24 21 18 15 12 9 6 3 27 100 80 60 40 20 Nivolumab (n=211) Chemotherapy (n=212) mPFS, months (95%CI) 4.2 (3.0, 5.6) 5.9 (5.4, 6.9) 1-year PFS rate, % 23.6 23.2 Months PFS, % HR 1.15 (95%CI 0.91, 1.45); p=0.2511 Nivolumab Chemotherapy Number at risk: Nivolumab 211 104 71 49 35 24 6 3 1 Chemotherapy 212 144 74 47 28 21 8 All randomised patients (≥1% PD-L1+): HR 1.17 (95%CI 0.95, 1.43) Socinski et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA7_PR

All randomised patients (≥1% PD-L1+): HR 1.07 (95%CI 0.86, 1.33) LBA7_PR: CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage IV/recurrent programmed death ligand 1 (PD-L1)–positive NSCLC – Socinski M, et al Key results (cont.) OS (≥5% PD-L1+) Months OS, % 24 21 18 15 12 9 6 3 30 100 80 60 40 20 27 Nivolumab Chemotherapy Nivolumab (n=211) Chemotherapy (n=212) Median OS, months (95%CI) 14.4 (11.7, 17.4) 13.2 (10.7, 17.1) 1-year OS rate, % 56.3 53.6 HR 1.02 (95%CI 0.80, 1.30) 60.4% in the chemotherapy arm had subsequent nivolumab therapy 43.6% in the nivolumab arm had subsequent systemic therapy Number at risk: Nivolumab 211 186 156 133 118 98 49 14 4 Chemotherapy 212 153 137 112 91 50 15 3 1 All randomised patients (≥1% PD-L1+): HR 1.07 (95%CI 0.86, 1.33) Socinski et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA7_PR

LBA7_PR: CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage IV/recurrent programmed death ligand 1 (PD-L1)–positive NSCLC – Socinski M, et al Key results (cont.) Nivolumab (n=211) Chemotherapy (n=212) ORR, % (95%CI) 26.1 (20.3, 32.5) 33.5 (27.2, 40.3) Best overall response, % CR PR SD PD Not determined 1.9 24.2 38.4 27.5 8.1 0.5 33.0 47.2 9.9 9.4 Median time to response, months (range) 2.8 (1.2, 13.2) 2.6 (1.2, 9.8) Median duration of response, months (95%CI) 12. 1 (8.8, NE) 5.7 (4.2, 8.5) Socinski et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA7_PR

Nivolumab did not improve PFS or OS compared with chemotherapy LBA7_PR: CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage IV/recurrent programmed death ligand 1 (PD-L1)–positive NSCLC – Socinski M, et al Key results (cont.) Conclusions Nivolumab did not improve PFS or OS compared with chemotherapy High PD-L1 expression subset was not planed and cannot be accurately measured/reported related to clinical characteristics imbalances AEs were consistent with reported data for nivolumab, with fewer grade 3–4 AEs than chemotherapy Nivolumab (n=267) Chemotherapy (n=263) Any grade Grade 3–4 Treatment-related AE, % Any SAE AE leading to discontinuation 71.2 17.2 9.7 17.6 13.1 7.9 92.4 18.3 13.3 50.6 15.6 6.5 Treatment-related deaths, n (%) 2 (0.7) 3 (1.1) Socinski et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA7_PR

Advanced NSCLC Not radically treatable stage III and stage IV Later lines

359O: First-in-human study of AC0010, a novel irreversible, mutant-selective EGFR inhibitor in patients with 1st generation EGFR TKI-resistant non-small cell lung cancer (NSCLC) – Zhang L, et al Study objective To evaluate the safety and efficacy of AC0010 in NSCLC patients with EGFR-TKI resistance Methods 52 EGFR mutation-positive advanced stage NSCLC patients who had resistance to EGFR TKIs were included; all patients had EGFR activated mutation and 87% had acquired T790M+ Oral administration of AC0010 either QD (50–350 mg), BID (175–300 mg) or TID (200 mg) Key results The majority of AEs were grade 1–2, and maximum tolerated dose was not reached Among all evaluated patients (including T790M negative patients), the ORR was 38.9% and DCR was 73% Dose exposure between 350 and 600 mg/day was considered as the efficacious dose, with ORR 55.6% and DCR 86.1% Conclusions AC0010 was well-tolerated with a good safety profile and showed promising anti-tumour activity in EGFR T790M+ NSCLC patients Better anti-tumour activities were seen with 250 mg BID and 300 mg BID and was recommended as the dosage in phase 2 studies Zhang et al. Ann Oncol 2016; 27 (suppl 6): abstr 359O

LBA42_PR: Ceritinib vs chemotherapy (CT) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with CT and crizotinib (CRZ): results from the confirmatory phase 3 ASCEND-5 study – Scagliotti G, et al Study objective To compare the efficacy of ceritinib vs. chemotherapy in ALK+ NSCLC patients pre-treated with chemotherapy and crizotinib Key patient inclusion criteria Locally advanced or metastatic ALK+ NSCLC Progressive disease WHO PS 0–2 Prior crizotinib (>1 course allowed) 1 or 2 prior chemotherapy regimens Measurable disease at baseline (n=231) Ceritinib 750 mg/day (n=115) Crossover following BIRC-confirmed PD Stratification WHO PS (0 vs.1–2) Brain metastases (yes vs. no) R 1:1 Chemotherapy Pemetrexed 500 mg/m2 (n=40) or docetaxel 75 mg/m2 (n=73) q3w Primary endpoint PFS (BIRC) Secondary endpoints OS, PFS (investigator), ORR, DCR, TTR BIRC, blinded independent review committee Scagliotti et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA42_PR

LBA42_PR: Ceritinib vs chemotherapy (CT) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with CT and crizotinib (CRZ): results from the confirmatory phase 3 ASCEND-5 study – Scagliotti G, et al Key results Median OS was 18.1 months (95%CI 13.4, 23.9) for ceritinib and 20.1 months (95%CI 11.9, 25.1) for chemotherapy (HR 1.0; 95%CI 0.67, 1.49) ORR (BIRC) was 39.1% (95%CI 30.2, 48.7) with ceritinib vs. 6.9% (95%CI 3.0, 13.1) with chemotherapy PFS (BIRC) 100 Treatment Median PFS, mo (95%CI) Events, n (%) Ceritinib 750 mg (n=115) 5.4 (4.1, 6.9) 83 (72.2) Chemotherapy (n=116) 1.6 (1.4, 2.8) 89 (76.7) 80 60 HR 0.49 (95%CI 0.36, 0.67) p<0.001 Probability of PFS, % 40 20 2 4 6 8 10 12 14 16 18 20 22 24 Time, months BIRC, blinded independent review committee Scagliotti et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA42_PR

LBA42_PR: Ceritinib vs chemotherapy (CT) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with CT and crizotinib (CRZ): results from the confirmatory phase 3 ASCEND-5 study – Scagliotti G, et al Key results (cont.) Diarrhoea, nausea and vomiting were higher with ceritinib than chemotherapy AEs led to discontinuation in 5.2% of the ceritinib patients and 6.9% of the chemotherapy patients Conclusions Compared with chemotherapy, ceritinib significantly improved PFS in patients with ALK+ NSCLC The safety profile of ceritinib was consistent with that reported in previous studies and compared unfavourably to chemotherapy in this trial AEs (occurring in >50% any grade), n (%) Ceritinib (n=115) Chemotherapy (n=113) All grades Grades 3/4 Diarrhoea 83 (72.2) 5 (4.3) 20 (17.7) 1 (0.9) Nausea 76 (66.1) 9 (7.8) 26 (23.0) 2 (1.8) Vomiting 60 (52.2) 6 (5.3) Scagliotti et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA42_PR

Ceritinib 750 mg/day (fasting, PO) 1208O: Phase 2 study of ceritinib in ALKi-naïve patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM) – Felip E, et al Study objective To evaluate the long-term efficacy and safety of ceritinib in ALK+ NSCLC patients previously-treated with up to 3 lines of prior chemotherapy, but ALK inhibitor naïve Key patient inclusion criteria Advanced or metastatic ALK+ NSCLC ALK inhibitor naïve ≤3 lines of chemotherapy with progression with last line WHO PS 0–2 (n=124) Ceritinib 750 mg/day (fasting, PO) PD / toxicity / other Primary endpoint ORR (investigator) Secondary endpoints ORR (BIRC), DoR, TTR, DCR, PFS, OS Felip et al. Ann Oncol 2016; 27 (suppl 6): abstr 1208O

Without brain metastases (n=75) 1208O: Phase 2 study of ceritinib in ALKi-naïve patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM) – Felip E, et al Key results Investigator assessment Total population (n=124) With brain metastases (n=49) Without brain metastases (n=75) ORR, n (%) [95%CI] 84 (67.7) [58.8, 75.9] 28 (57.1) [42.2, 71.2] 56 (74.7) [63.3, 84.0] DCR, n (%) [95%CI] 112 (90.3) [83.7, 94.9] 43 (87.8) [75.2, 95.4] 69 (92.0) [83.4, 97.0] Median PFS, months [95%CI] 16.6 [11.0, 22.1] 10.8 [8.3, 16.6] 19.6 [14.5, NE] Median DOR, months [95%CI] 22.1 [14.8, NE] Median OS, months Not yet reached 24-month OS rate, % [95%CI] 67.5 [58.0, 75.2] BIRC assessment 79 (63.7) [54.6, 72.2] 107 (86.3) [79.0, 91.8] 18.4 [10.9, 26.3] Felip et al. Ann Oncol 2016; 27 (suppl 6): abstr 1208O

8.9% of patients discontinued treatment due to AEs Conclusions 1208O: Phase 2 study of ceritinib in ALKi-naïve patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM) – Felip E, et al Key results (cont.) Grade 3 or 4 AEs occurred in 85.5% of patients, the most common were ALT increased (21.0%), GGT increased (19.4%) and AST increased (9.7%) Drug-related SAEs occurred in 11.3% patients, the most common were pericarditis, nausea and vomiting 8.9% of patients discontinued treatment due to AEs Conclusions In the long-term follow-up of the ASCEND-3 study, ceritinib resulted in robust ORR and exhibited a prolonged PFS and OS in ALK inhibitor- naive patients Ceritinib was also shown to be active in patients with brain metastases The AEs seen were consistent with the reported safety profile of ceritinib Felip et al. Ann Oncol 2016; 27 (suppl 6): abstr 1208O

1201O: Gefitinib/chemotherapy vs chemotherapy in EGFR mutation-positive NSCLC after progression on 1st line gefitinib (IMPRESS study): Final overall survival (OS) analysis – Soria J, et al Study objective To evaluate the impact of continuing gefitinib therapy in addition to cisplatin + pemetrexed chemotherapy in patients with advanced/metastatic NSCLC Key patient inclusion criteria Stage IIIB/IV EGFR+ advanced NSCLC Chemotherapy naïve Achieved CR/PR ≥4 months or SD >6 months with first-line gefitinib Disease progression <4 weeks prior to study randomisation WHO PS 0−1 (n=265) Gefitinib 250 mg/day + cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 (n=133) PD / toxicity R 1:1 Placebo + cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 (n=132) PD / toxicity Primary endpoint PFS Secondary endpoints OS, ORR, DCR, safety/tolerability, HRQoL Soria et al. Ann Oncol 2016; 27 (suppl 6): abstr 1201O

Time since randomisation, months 1201O: Gefitinib/chemotherapy vs chemotherapy in EGFR mutation-positive NSCLC after progression on 1st line gefitinib (IMPRESS study): Final overall survival (OS) analysis – Soria J, et al Key results Final OS (66% maturity) Gefitinib (n=133) Placebo (n=132) Median OS, months 13.4 19.5 Number of events, n (%) 94 (71) 82 (62) HR 1.44 (95%CI 1.07, 1.94); p=0.016 1.0 0.8 0.6 Probability of OS 0.4 0.2 Gefitinib + CT (n=133) Placebo + CT (n=132) 0.0 4 8 12 16 20 24 28 32 36 40 44 Time since randomisation, months Soria et al. Ann Oncol 2016; 27 (suppl 6): abstr 1201O

Time since randomisation, months 1201O: Gefitinib/chemotherapy vs chemotherapy in EGFR mutation-positive NSCLC after progression on 1st line gefitinib (IMPRESS study): Final overall survival (OS) analysis – Soria J, et al Key results (cont.) Conclusion Final OS data from the IMPRESS study warn against continued treatment with first-generation EGFR TKIs beyond radiological disease progression T790M mutation-positive Gefitinib + CT (n=81) Placebo + CT (n=61) Median OS, months 10.8 14.1 Number of events, n (%) 63 (77.8) 44 (72.1) HRa 1.49 (95%CI 1.02, 2.21) OS by T790M mutation 1.0 0.8 0.6 0.4 0.2 0.0 4 Time since randomisation, months 8 12 16 Probability of OS 20 24 28 32 36 40 44 Gefitinib – T790M negative Placebo – T790M negative 81 81 46 59 66 57 40 51 49 54 35 47 33 34 29 41 23 25 28 24 15 22 23 29 9 12 14 21 3 8 8 12 2 6 7 6 1 2 4 2 0 2 2 1 0 0 0 0 74 61 46 58 61 51 37 47 40 40 34 44 28 28 28 41 21 24 27 30 13 16 19 26 5 11 11 12 2 8 7 10 2 4 4 3 0 1 0 0 Gefitinib – T790M positive Placebo – T790M positive T790M mutation-negative Gefitinib + CT (n=46) Placebo + CT (n=59) Median OS, months 21.4 22.5 Number of events, n (%) 27 (58.7) 30 (50.8) HRa 1.15 (95%CI 0.68, 1.94) Number at risk: aPrimary Cox analysis with covariates Soria et al. Ann Oncol 2016; 27 (suppl 6): abstr 1201O

1203PD: LURET study: Phase 2 study of vandetanib in patients with advanced RET-rearranged non-small cell lung cancer (NSCLC) – Horiike A, et al Study objective To assess the efficacy and safety of vandetanib in advanced RET-rearranged NSCLC Methods A single-arm phase 2 study of vandetanib (300 mg/day orally) in patients with advanced RET-rearranged NSCLC with ≥1 prior chemotherapy Key results 34 RET-positive patients were identified (2% of those screened); 19 were enrolled into the study (ITT population) with 17 in the primary analysis population ORR was 53% (90%CI 31, 74; p=0.04) with 9 partial responses for the primary analysis; ORR was 47% (90%CI 24, 71) in the ITT population In the ITT population, DCR was 90% (95%CI 67, 99), median PFS was 4.7 months (95%CI 2.8, 8.5) and 1-year OS rate was 47% (95%CI 21, 69) In subgroup analyses, CCDC6-RET mutations had ORR 83% (95%CI 36, 99.6) and median PFS 8.3 months (95%CI 4.7, 8.5), and KIF5B-RET mutations had ORR 20% (95%CI 3, 56) and median PFS 2.9 months (95%CI 1.1, 15.7) AEs grade ≥3 (occurring in >10%) included hypertension (58%), acneiform rash (16%), diarrhoea (11%) and QTc prolongation (11%) Conclusions Vandetanib showed anti-tumour activity in patients with advanced RET-rearranged NSCLC Data suggest that tumours expressing CCDC6-RET mutations may respond better to vandetanib than tumours with KIF5B-RET Horiike et al. Ann Oncol 2016; 27 (suppl 6): abstr 1203PD

1204PD: Phase 2 study of lenvatinib (LN) in patients (pts) with RET fusion-positive adenocarcinoma of the lung – Velcheti V, et al Study objective To evaluate the efficacy and safety of lenvatinib, a multikinase inhibitor Methods Open-label, phase 2 study of lenvatinib (24 mg/day PO) in patients with RET fusion- positive lung adenocarcinoma Key results 25 patients with RET fusion-positive NSCLC were enrolled; 28% had received previous RET-targeted therapy ORR was 16% (all confirmed PRs) and DCR was 76% mPFS was 7.3 months (95%CI 3.6, 10.2) Grade ≥3 treatment-related AEs were reported in 21 (84.0%) patients. TEAEs of 20.0%, 64.0% and 76.0% were associated with drug withdrawal, dose reduction and dose interruption, respectively Commonly reported AEs (any grade occurring in >50%) included hypertension (68%), nausea (60%), decreased appetite and diarrhoea (both 52%) Conclusion In patients with RET fusion-positive NSCLC lenvatinib showed clinical activity, including those who had previously received RET-targeted therapy Velcheti et al. Ann Oncol 2016; 27 (suppl 6): abstr 1204PD

1205PD: Ceritinib in ROS1-rearranged non-small-cell lung cancer: A Korean nationwide phase II study – Lim S, et al Study objective To evaluate the efficacy and safety of ceritinib in patients with advanced ROS1-rearranged NSCLC Methods A phase 2 study of ceritinib 750 mg/day PO after fasting, in patients with advanced NSCLC who tested positive for ROS1 rearrangement and had previously received ≥1 line of platinum-based chemotherapy Key results 404 patients were screened and 32 ROS1-positive patients were enrolled ORR was 62% with 1 CR and 19 PRs; median DoR was 18.4 months (95%CI 8.0, 18.4) and median PFS was 10.0 months (95%CI 2.5, 17.4) Median OS was not reached by time of data cut-off Seven ROS fusion partners (including ROS1-CD74, ROS1-SLC34A2 and ROS1-EZR) were identified in the 11 tumours tested The most frequently reported AEs occurring in >50% were diarrhoea (78%), nausea (59%), anorexia (56%) and vomiting (53%), but drug-related AEs were mainly grades 1–2 Conclusion Ceritinib showed significant clinical activity in advanced ROS1-positive NSCLC patients, with a safety profile consistent to that previously reported Lim et al. Ann Oncol 2016; 27 (suppl 6): abstr 1205PD

No grade 4 or 5 TRAEs were reported 1206PD: Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Updated results from PROFILE 1001 – Shaw A, et al Study objective To assess the safety and anti-tumour activity of crizotinib in ROS1-positive NSCLC Methods Phase 1 study of crizotinib (250 mg BID PO) in patients with ROS1-positive advanced NSCLC Key results 53 patients were enrolled with median treatment duration of 23.2 months Vision disorder was the most frequently reported TRAE (84.9%), followed by nausea (49.1%), oedema (45.3%) and diarrhoea (41.5%) No grade 4 or 5 TRAEs were reported ORR by investigator was 69.8% (95%CI 55.7, 81.7), with 5 CRs and 32 PRs Median PFS was 19.3 months (95%CI 14.8, not reached) Median OS was not reached at median follow-up of 25.4 months Conclusion Crizotinib was well tolerated and showed significant clinical activity with acceptable safety profile in patients with ROS1-positive advanced NSCLC Shaw et al. Ann Oncol 2016; 27 (suppl 6): abstr 1206PD

Atezolizumab 1200 mg IV q3w (n=425) LBA44_PR: Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC – Barlesi F, et al Study objective To evaluate the efficacy and safety of atezolizumab vs. docetaxel in patients with previously treated NSCLC Atezolizumab 1200 mg IV q3w (n=425) Key patient inclusion criteria Locally advanced or metastatic NSCLC 1–2 prior lines of chemotherapy including at least 1 platinum based Any PD-L1 status (n=1225) PD / loss of benefit Stratification PD-L1 status Prior chemotherapy regimens (1 vs. 2) Histology R Docetaxel 75 mg/m2 IV q3w (n=425) PD Primary endpoint OS in ITT and PD-L1-expression on ≥1% TC or IC Secondary endpoints ORR, PFS, DoR, safety Barlesi et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA44_PR

LBA44_PR: Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC – Barlesi F, et al Key results OS, ITT (n=850) OS, % HR 0.73a (95%CI 0.62, 0.87) p=0.0003 Minimum follow-up = 19 months (95%CI 8.6, 11.2) (95%CI 11.8, 15.7) Median 9.6 mo Median 13.8 mo Months Atezolizumab Docetaxel Number at risk: 425 407 382 363 342 326 305 279 260 248 234 223 218 205 198 188 175 163 157 141 116 74 54 41 28 15 4 1 390 365 336 311 286 263 219 195 179 168 151 140 132 123 104 98 90 70 51 37 16 6 3 236 100 27 21 80 24 18 60 12 40 9 20 aStratified HR Barlesi et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA44_PR

LBA44_PR: Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC – Barlesi F, et al Key results (cont.) OS by PD-L1 expression mOS, months Atezolizumab Docetaxel Subgroup n=425 TC3 or IC3 TC2 / 3 or IC2 / 3 TC1 / 2 / 3 or IC1 / 2 / 3a TC0 and IC0 20.5 16.3 15.7 12.6 8.9 10.8 10.3 13.8 9.6 ITTa 0.2 1 2 Hazard Ratioa In favour of atezolizumab docetaxel 0.41 0.67 0.74 0.75 0.73 On-study prevalence 0% 20% 40% 80% 60% 100% 16% 31% 55% 45% aStratified HRs for ITT and TC1 / 2 / 3 or IC1 / 2 / 3. Unstratified HR for subgroups Barlesi et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA44_PR

LBA44_PR: Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC – Barlesi F, et al Key results (cont.) PFS, ITT mPFS, months 100 HR 0.95a Atezolizumab Docetaxel Median 2.8 mo (95%CI 2.6, 3.0) (95%CI 0.82, 1.10) 80 p=0.4928b Subgroup n=425 n=425 0.63 60 Median 4.0 mo (95%CI 3.3, 4.2) TC3 or IC3 TC2 / 3 or IC2 / 3 TC1 / 2 / 3 or IC1 / 2 / 3a TC0 and IC0 4.2 4.1 2.8 2.6 3.3 3.6 4.1 4.0 PFS, % Atezolizumab 0.76 40 Docetaxel 0.91 20 1.00 0.95 3 6 9 12 15 18 21 24 27 ITTa 2.8 4.0 Months Number at risk Atezolizumab Docetaxel 425 395 385 243 283 190 223 181 198 139 142 128 110 119 91 111 81 99 60 92 50 80 41 75 38 64 29 59 27 53 23 51 19 49 17 45 16 29 13 22 11 12 5 9 4 7 2 2 1 1 0.4 1 2 Hazard Ratioa In favour of atezolizumab In favour of docetaxel Investigator-assessed PFS per RECIST v1.1 aStratified HRs for ITT and TC1 / 2 / 3 or IC1 / 2 / 3. Unstratified HR for subgroups; bp-values for descriptive purposes only Barlesi et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA44_PR

LBA44_PR: Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC – Barlesi F, et al Key results (cont.) Conclusions Atezolizumab improved OS in all patients, and benefit was seen regardless of PD-L1 expression levels (HR 0.75 in <1% PD-L1 expression population and 0.41 in ≥50% TC or ≥10% IC expression population) OS benefit was consistent across subgroups, including histology (HR 0.73 for both), patients with CNS mets (HR 0.54) and never smokers (HR 0.71) Atezolizumab was well tolerated and had a favourable safety profile compared with docetaxel Atezolizumab Docetaxel ORR, % TC3 or IC3 TC2 / 3 or IC2 / 3 TC1 / 2 / 3 or IC1 / 2 / 3 TC0 or IC0 14 31 22 18 8 13 11 16 Duration of response ITT Ongoing response, % Median, months TC0 and IC0 52 16.3 47 16.0 71 NE 6.2 29 Barlesi et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA44_PR

Placebo + docetaxel 75 mg/m2 IV q3w (up to 6 cycles) LBA45: Top-line results from SUNRISE: A phase III, randomized, double-blind, placebo-controlled multicenter trial of bavituximab plus docetaxel in patients with previously treated stage IIIb/IV non-squamous non small cell lung cancer – Spigel DR, et al Study objective To evaluate bavituximab + docetaxel compared with placebo + docetaxel in patients with previously treated stage IIIb/IV nonsquamous NSCLC Key patient inclusion criteria Stage IIIb/IV nonsquamous NSCLC 1 prior platinum-based doublet for advanced disease Progressed on appropriate targeted therapy if known EGFR/ALK mutation ECOG PS 0–1 Prior immunotherapy allowed (n=597) Bavituximab 3 mg/kg qw + docetaxel 75 mg/m2 IV q3w (up to 6 cycles) (n=425) PD / toxicity Stratification Region Disease stage Prior maintenance/targeted therapy R Placebo + docetaxel 75 mg/m2 IV q3w (up to 6 cycles) (n=425) PD / toxicity Primary endpoint OS Secondary endpoints ORR, PFS, safety, PK, QoL, β2-GP1 as exploratory biomarker Spigel et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA45

LBA45: Top-line results from SUNRISE: A phase III, randomized, double-blind, placebo-controlled multicenter trial of bavituximab plus docetaxel in patients with previously treated stage IIIb/IV non-squamous non small cell lung cancer – Spigel DR, et al Key results Safety profile was generally similar between the two treatment groups Grade 3/4 febrile neutropenia was slightly higher for bavituximab vs. docetaxel (8% vs. 5%) Trend for prolonged survival with bavituximab in subgroups with high β2-GP1 at baseline (exploratory analysis only) Conclusions The safety profile of bavituximab + docetaxel is similar to placebo + docetaxel The addition of bavituximab to docetaxel did not result in improvement in OS Preliminary data suggest β2-GP1 levels may provide a biomarker for patients who may be more likely to benefit from treatment with bavituximab 1.0 OS (ITT population) Treatment Median, months No. of events Bavituximab 10.7 (8.6, 11.5) 169 Placebo 10.8 (9.2, 12.6) 161 0.8 0.6 OS, % 0.4 HR (95%CI) 1.10 (0.89, 1.37) p-value 0.382 0.2 3 6 9 12 15 18 21 24 27 Time, months Spigel et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA45

LBA47_PR: Selumetinib in combination with docetaxel as second-line treatment for patients with KRAS-mutant advanced NSCLC: Results from the phase III SELECT-1 trial – Jänne PA, et al Study objective To assess the clinical benefit of selumetinib + docetaxel compared with placebo + docetaxel in patients with locally advanced or metastatic KRAS-mutant NSCLC Key patient inclusion criteria KRAS-mutant stage IIIb/IV NSCLC Failed first-line therapy WHO PS 0–1 Excluded if >1 previous anti-cancer drug regimen for advanced disease (n=510) Selumetinib 75 mg BID PO + docetaxel 75 mg/m2 IV D1 q3w (up to 6 cycles)* (n=254) PD / toxicity / other Stratification WHO PS (0/1) Histology (squamous/nonsquamous) R Selumetinib or placebo Placebo + docetaxel 75 mg/m2 IV D1 q3w (up to 6 cycles)* (n=256) PD / toxicity / other Primary endpoint PFS Secondary endpoints OS, ORR, DoR, safety *All received prophylactic G-CSF Jänne et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA47_PR

Time from randomisation, months LBA47_PR: Selumetinib in combination with docetaxel as second-line treatment for patients with KRAS-mutant advanced NSCLC: Results from the phase III SELECT-1 trial – Jänne PA, et al Key results OS was not significantly improved with selumetinib + docetaxel compared with placebo + docetaxel, 8.7 vs. 7.9 months (HR 1.05 [95%CI 0.85,1.30]) in KRAS- mutant advanced NSCLC PFS Time from randomisation, months 254 256 1 219 231 2 164 154 3 128 112 4 109 97 5 74 68 6 48 50 7 31 33 8 27 28 SEL + DOC PBO + DOC 9 20 10 15 13 11 14 12 16 17 18 19 21 22 23 24 25 26 SEL + DOC (n=254) PBO + DOC (n=254) Events, n (%) 218 (86) 229 (89) Median, months 3.9 2.8 HR (95%CI) 2-sided p-value 0.93 (0.77, 1.12) 0.44 1.0 0.8 0.6 Probability of PFS 0.4 0.2 Patients at risk: SEL + DOC PBO + DOC Jänne et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA47_PR

Selumetinib + docetaxel (n=251) Placebo + docetaxel (n=254) LBA47_PR: Selumetinib in combination with docetaxel as second-line treatment for patients with KRAS-mutant advanced NSCLC: Results from the phase III SELECT-1 trial – Jänne PA, et al Key results (cont.) Conclusions Selumetinib + docetaxel did not significantly improve PFS or OS compared with docetaxel + placebo in KRAS-mutant advanced NSCLC The safety profile of selumetinib + docetaxel was consistent with data for docetaxel and selumetinib Selumetinib + docetaxel (n=251) Placebo + docetaxel (n=254) Any AE Grade 3 249 (99) 169 (67) 242 (95) 115 (45) Any SAE Related to selumetinib/placebo Related to docetaxel 124 (49) 50 (20) 42 (17) 82 (32) 14 (6) 24 (9) Any AE leading to hospitalisation 116 (46) 76 (30) Any AE with outcome of death 16 (6) 9 (4) Grade 3 AE occurring in ≥5%, n (%) Diarrhoea Asthenia Dyspnoea Anaemia Neutropenia 18 (7) 22 (9) 20 (8) 12 (5) 7 (3) 6 (2) 11 (4) 10 (4) Jänne et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA47_PR

Interim analysis Final analysis LBA38: Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P) – Herbst RS, et al Study objective To assess the safety and tolerability of adding ramucirumab to pembrolizumab Phase 1a: DLT assessment (n=6–12) Primary: Safety and tolerability Secondary: PK Phase 1b: Cohort expansion (n=155) Treatment up to 35 cycles, until PD or discontinuation for other reason Schedule 1: Gastric/GEJ, BTC 3+3 design (n=3–6) Ramucirumab 8 mg/kg D1, 8 Pembrolizumab 200 mg D1 Both IV q3w Cohort A: 15 Gastric/GEJ (2nd-3rd line) Cohort A1: 25 BTC (2nd-3rd line) Cohort A2: 25 Gastric/GEJ (1st line) Schedule 2: Gastric/GEJ, NSCLC, UC 3+3 design (n=3–6) Ramucirumab 10 mg/kg D1 Pembrolizumab 200 mg D1 Both IV q3w Interim analysis Final analysis Cohort B: 15 Gastric/GEJ (2nd-3rd line) Cohort C: 25 NSCLC (2nd-4th line) Cohort D: 25 UC (2nd-4th line) Cohort E: 25 NSCLC (1st line) Key inclusion criteria ECOG PS 0–1, squamous or nonsquamous NSCLC with PD on prior therapy (Cohort C) Patients with known EGFR or ALK mutations eligible only if they have received prior targeted therapy Herbst et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA38

There were no grade 4/5 TRAEs LBA38: Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P) – Herbst RS, et al Key results There were no grade 4/5 TRAEs Objective response occurred in 8 (30%) patients (1 unconfirmed) and are ongoing in all responders; DCR was 85% Conclusions There were no new safety signals with ramucirumab + pembrolizumab, with a low incidence of grade 3 AEs In squamous and nonsquamous NSCLC there was promising clinical activity with the ramucirumab + pembrolizumab combination TRAE of interest, n (%) Cohort C: NSCLC (n=27) Any grade Grade 3 Endocrine disorders 6 (22) 1 (4) Hypertension 5 (19) - Diarrhoea 3 (11) Infusion-related reaction 2 (7) Elevated transaminase Proteinuria Herbst et al. Ann Oncol 2016; 27 (suppl 6): abstr LBA38

Other malignancies SCLC and mesothelioma

Placebo BID PO (3 days on/4 days off) + paclitaxel 80 mg/m2 D1, 8, 15 1423O: Randomized phase 2 study of investigational aurora A kinase (AAK) inhibitor alisertib (MLN8237) + paclitaxel (P) vs placebo + P as second line therapy for small-cell lung cancer (SCLC) – Owonikoko TK, et al Study objective To investigate the efficacy and safety of alisertib + paclitaxel in SCLC Key patient inclusion criteria Histologically/cytologically confirmed SCLC Relapse <180 days after last dose of platinum-based chemotherapy ECOG PS 0–1 (n=178) Alisertib 40 mg BID PO (3 days on/4 days off) + paclitaxel 60 mg/m2 D1, 8, 15 (n=89) PD / toxicity Stratification Type of relapse (sensitive vs. resistant/refractory) Brain metastases at baseline R 1:1 Placebo BID PO (3 days on/4 days off) + paclitaxel 80 mg/m2 D1, 8, 15 (n=89) PD / toxicity Primary endpoint PFS (ITT population) Secondary endpoints Safety/tolerability, OS, ORR, DCR, DoR, biomarkers (c-Myc expression) Owonikoko et al. Ann Oncol 2016; 27 (suppl 6): abstr 1423O

Primary endpoint: PFS (ITT population) Median PFS, days (months) 1423O: Randomized phase 2 study of investigational aurora A kinase (AAK) inhibitor alisertib (MLN8237) + paclitaxel (P) vs placebo + P as second line therapy for small-cell lung cancer (SCLC) – Owonikoko TK, et al Key results Primary endpoint: PFS (ITT population) 1.0 Treatment Median PFS, days (months) Alisertib + paclitaxel 101 (3.32) Placebo + paclitaxel 66 (2.17) 0.8 0.6 IVRS HR (95%CI) 0.77 (0.557, 1.067) Log rank p=0.113 Corrected* HR (95%CI) 0.71 (0.509, 0.985) Log rank p=0.038 Survival probability 0.4 0.2 0.0 30 60 90 120 150 180 210 240 270 300 Survival time, days 89 89 74 65 55 45 41 27 28 19 13 12 10 8 6 4 3 3 0 3 0 0 Group Alisertib Placebo HR (95%CI) p-value PFS (resistant/refractory relapse patients), days 87 50 0.659 (0.442, 0.983) 0.0372 OS, days 186 165 0.93 (0.652, 1.341) 0.714 ORR, % 22 18 DCR, % 58 46 *Stratification definition of sensitive was amended after 30% of patients had been enrolled but prior to analysis to better reflect the guidelines Owonikoko et al. Ann Oncol 2016; 27 (suppl 6): abstr 1423O

Rates of AEs were higher with alisertib 1423O: Randomized phase 2 study of investigational aurora A kinase (AAK) inhibitor alisertib (MLN8237) + paclitaxel (P) vs placebo + P as second line therapy for small-cell lung cancer (SCLC) – Owonikoko TK, et al Key results (cont.) Rates of AEs were higher with alisertib Conclusions Alisertib + paclitaxel showed favourable PFS vs. paclitaxel alone with a significant difference observed in the protocol redefined subgroup of resistant/refractory tumours The combination did not reach statistical significance for OS, ORR and DCR Greater toxicity was observed with alisertib + paclitaxel vs. paclitaxel alone Alisertib (n=87) Placebo (n=89) Grade >3 AEs, % 76 51 Drug-related grade >3 AEs, % 67 25 Drug-related serious AEs, % 32 7 AEs leading to discontinuation of study drug, % 15 6 Owonikoko et al. Ann Oncol 2016; 27 (suppl 6): abstr 1423O

1425PD: Clinical activity, safety and predictive biomarkers results from a phase Ia atezolizumab (atezo) trial in extensive-stage small cell lung cancer (ES-SCLC) – Sequist LV, et al Study objective To assess the safety and clinical therapy of atezolizumab in extensive stage (ES)-SCLC Methods Phase 1a study of atezolizumab monotherapy 15 mg/kg or 1200 mg q3w IV in ES-SCLC Tumours were assessed by RECIST v1.1 criteria and irRC assessments Key results As of March 31, 2016, 17 patients were enrolled and had a minimum follow-up of 10 months There were seven grade 3–4 TRAEs in 2 patients and one grade 5 (hepatic failure) The ORR was 5.9% (95%CI 0.2, 28.7) by RECIST and 17.6% (95%CI 3.8, 43.4) by irRC mPFS was 1.5 months (95%CI 1.2, 2.7) by RECIST and 2.9 months (95%CI 1.2, 6.1) by irRC mOS was 5.9 months (95%CI 4.3, 12.6) There was a trend toward improved PFS (per irRC) and OS in tumours with higher expression (≥median) of PD-L1 mRNA and T-effector gene signature Conclusions Atezolizumab in ES-SCLC had a tolerable safety profile Modest single-agent activity of atezolizumab in ES-SCLC is reported Sequist et al. Ann Oncol 2016; 27 (suppl 6): abstr 1425PD

1426PD: Phase II study of roniciclib in combination with cisplatin/etoposide or carboplatin/etoposide as first-line therapy in subjects with extensive-disease small cell lung cancer (ED-SCLC) – Reck M, et al Study objective To evaluate the efficacy and safety of roniciclib in combination with cisplatin + etoposide or carboplatin + etoposide in extensive-disease (ED)-SCLC Roniciclib 5 mg BID 3 days-on/4 days-off q3w* (n=70) PD / toxicity / other Key patient inclusion criteria Histologically or cytologically confirmed ED-SCLC ECOG 0–1 Life expectancy ≥12 weeks Serum sodium ≥120 mmol/L (n=140) Stratification Gender Serum lactate dehydrogenase (≤2.5/>2.5 x upper limit of normal) R Placebo BID 3 days-on/4 days-off q3w* (n=70) PD / toxicity / other Primary endpoint PFS Secondary endpoints OS, TTP, ORR and safety *For 6 cycles combined with standard chemotherapy (etoposide [100 mg/m2 D1, 2, 3] with either cisplatin [75 mg/m2 D1] or carboplatin [5 mg/mL/min D1] q3w) followed by roniciclib or placebo monotherapy Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr 1426PD

1426PD: Phase II study of roniciclib in combination with cisplatin/etoposide or carboplatin/etoposide as first-line therapy in subjects with extensive-disease small cell lung cancer (ED-SCLC) – Reck M, et al Key results No significant differences with roniciclib vs. placebo were seen in the efficacy endpoints Median PFS 4.9 vs. 5.5 months (HR 1.242; 95%CI 0.820, 1.881; p=0.8653) Median OS 10.6 vs. 10.6 months (HR 1.430; 95%CI 0.785, 2.606; p=0.8691) Median TTP 5.4 vs. 5.5 months (HR 1.047; 95%CI 0.665, 1.648; p=0.5900) ORR 60.6% vs. 74.6% (p=0.9685) The incidence of serious AEs was higher in the roniciclib group (55.7% vs. 34.3%) There were 9 fatal AEs in the roniciclib arm (2 attributed to roniciclib: sepsis and bronchopulmonary haemorrhage) vs. 1 in the placebo arm Conclusion Addition of roniciclib to standard-of-care chemotherapy in ED-SCLC patients increased toxicity without improving efficacy TEAEs (occurring in >50% any grade), n (%) Roniciclib (n=70) Placebo (n=70) Any Grade 3 Grade 4 Nausea 46 (65.7) 5 (7.1) 33 (47.1) 2 (2.9) Vomiting 43 (61.4) 7 (10.0) 14 (20.0) 1 (1.4) Fatigue 39 (55.7) 27 (38.6) 4 (5.7) Decreased neutrophil count 38 (54.3) 13 (18.6) 22 (31.4) 45 (64.3) 18 (25.7) 23 (32.9) Reck et al. Ann Oncol 2016; 27 (suppl 6): abstr 1426PD

1179PD: Low dose CT scan screening versus empiric surveillance in asbestos exposed subjects: Update of ATOM 002 study – Fasola G, et al Study objective To evaluate low-dose CT scan screening in reducing mortality for lung cancer and/or malignant pleural mesothelioma in asbestos-exposed former workers Methods Prospective non-randomised study of 2433 occupationally asbestos-exposed men with follow-up from 2002 to 2011 A Cox regression model was used for all-cause, all cancers, lung cancer and pleural mesothelioma survival Multivariate models were adjusted for smoking habits, age, level of asbestos exposure and Charlson-Quan comorbidity index Key results 926 men were allocated to the low-dose CT scan screening cohort and 1507 to the standard follow-up cohort Lung cancer crude mortality was 99.4 per 100,000 person-year in the low-dose CT scan screening cohort compared with 430.4 per 100,000 person-year in the standard follow-up cohort Fasola et al. Ann Oncol 2016; 27 (suppl 6): abstr 1179PD

Hazard ratio (multivariate) 1179PD: Low dose CT scan screening versus empiric surveillance in asbestos exposed subjects: Update of ATOM 002 study – Fasola G, et al Key results (cont.) There was a significant reduction in lung cancer and all-cause mortality with low-dose CT scan screening, with no difference in all cancers or pleural mesothelioma mortality There was also a reduction in lung cancer mortality compared to the general Italian population in the CT scan screening population (standardised mortality ratio 0.51; 95%CI 0.22, 1.01) Conclusion In this observational study, compared with national figures, low-dose CT scan screening reduced the risk of death from lung cancer in asbestos exposed men All causes HR 0.61; 95%CI 0.44, 0.84 All cancers HR 0.97; 95%CI 0.62, 1.50 Lung cancer HR 0.41; 95%CI 0.17, 0.96 Cancer of pleura HR 0.86; 95%CI 0.31, 2.41 0.0 0.5 1.0 1.5 2.0 2.5 3.0 Hazard ratio (multivariate) Fasola et al. Ann Oncol 2016; 27 (suppl 6): abstr 1179PD

Other malignancies Rare tumours

1509PD: Quality of resection and outcome in stage III thymic epithelial tumors (TET): A retrospective analysis of 150 cases from the national network RYTHMIC experience – Bluthgen MV, et al Study objective To evaluate the value of recommendations made by the board of the RYTHMIC network for the management of stage III thymic epithelial tumours (TET) Methods A retrospective analysis of 150 patients with stage III TET was conducted; this analysis included patients whose cases were discussed at the RYTHMIC board between January 2012 and December 2015 Clinical, pathologic and surgical data were prospectively collected in a central database Survival rates were based on Kaplan-Meier estimation, and DFS and OS were evaluated using Cox proportional hazard models Baseline characteristics The majority of patients were male (57%); median age was 62 [range 18–91] years Thymoma A–B2 and thymoma B3–thymic carcinoma were reported in 51% and 47% of patients, respectively Overall, 23% of patients displayed autoimmune disease (predominantly myasthenia 26 of 34 patients) Bluthgen et al. Ann Oncol 2016; 27 (suppl 6): abstr 1509PD

1509PD: Quality of resection and outcome in stage III thymic epithelial tumors (TET): A retrospective analysis of 150 cases from the national network RYTHMIC experience – Bluthgen MV, et al Key results A total of 134 (89%) patients received surgery Rate of complete resection (R0) was 53% 90 (60%) patients received postoperative radiotherapy 26 (68%) patients received induction chemotherapy Overall survival for overall population Disease-free survival for overall population 1.0 1.0 0.8 0.8 0.6 0.6 Probability of overall survival Probability of disease-free survival 0.4 5-year OS: 88% 10-year OS: 68% Median follow-up: 23.4 months (range 0.3–266.5) 0.4 5-year DFS: 32% 10-year DFS: 8% Median DFS: 43.9 months (95%CI 35.4, 52.3) 0.2 0.2 0.0 0.0 12 24 36 48 60 72 84 96 108 120 12 24 36 48 60 72 84 96 108 120 Time, months Time, months Number at risk Number at risk 150 97 24 54 39 32 25 21 19 16 11 150 90 57 36 21 13 11 8 5 4 3 Bluthgen et al. Ann Oncol 2016; 27 (suppl 6): abstr 1509PD

Disease-free survival 1509PD: Quality of resection and outcome in stage III thymic epithelial tumors (TET): A retrospective analysis of 150 cases from the national network RYTHMIC experience – Bluthgen MV, et al Key results (cont.) Conclusions Improved outcomes are observed with surgery followed by radiotherapy, regardless of R0 Patients with stage III TET initially considered ineligible for surgery should be reassessed for resection following induction chemotherapy Multivariate analysis in overall population Overall survival HR (95%CI) p-value Histology (A–B2 vs. B3–TC) 0.19 (0.05, 0.70) 0.02 Modality surgery (vs. no surgery) 0.04 (0.01, 0.20) <0.001 Multivariate analysis in surgical population Disease-free survival HR (95%CI) p-value Histology (A–B2 vs. B3–TC) 0.50 (0.30, 0.90) 0.02 Adjuvant radiotherapy (vs. no radiotherapy) 0.40 (0.20, 1.00) 0.05 Bluthgen et al. Ann Oncol 2016; 27 (suppl 6): abstr 1509PD

1510PD: Pathological central review of 400 thymic epithelial tumors (TET): The national network RYTHMIC experience – Molina T, et al Study objective To describe the discordances in institution and review panel diagnoses of thymic epithelial tumours (TET) and the impact on disease management Methods A central review of 400 patients diagnosed with TET between January 2012 and December 2015 was conducted by a panel of 10 expert pathologists Agreement or disagreement between the initial institution and the panel review was assessed according to WHO 2004/2015 guidelines for histologic typing, and Masaoka- Koga and the new ITMIG proposals for staging Discordances were classified as: “Major” when disagreement between panel review and the initial institution would have changed the therapy or management of patients “Minor” when disagreement between panel review and the initial institution would not have changed the therapy or management of patients Key results Overall, 178 discordances were identified in 159 (40%) patients 118 discordances concerned histological diagnosis 60 discordances concerned stage Molina et al. Ann Oncol 2016; 27 (suppl 6): abstr 1510PD

Total discordances according to stage before and after central review 1510PD: Pathological central review of 400 thymic epithelial tumors (TET): The national network RYTHMIC experience – Molina T, et al Key results (cont.) Sub-diagnosis of stage III was the most frequently observed discordance 31 occurrences of major discordances were observed in 29 (7%) patients In 17 cases, adjuvant radiotherapy should have been recommended In 1 case, adjuvant radiotherapy should not have been recommended In 7 cases, primary treatment should have been modified In 4 cases, follow-up treatment should have been modified Conclusion These results indicate the importance of expert histopathological panel diagnosis for thymic malignancies and the need for improved decision making, particularly with regard to the application of postoperative radiotherapy Total discordances according to stage before and after central review Total discordances according to histology before and after central review Local Review I IIA IIB III IVA IVB A AB B1 B2 B3 TC NOS Other Other diagnosis -30 -20 -10 10 20 30 -40 -30 -20 -10 10 20 30 40 Molina et al. Ann Oncol 2016; 27 (suppl 6): abstr 1510PD

Pasireotide 60 mg/month + everolimus 10 mg/day 416O: Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Results from the randomized, phase 2 LUNA study – Ferolla P, et al Study objective To evaluate the efficacy and safety of everolimus, pasireotide and pasireotide + everolimus in patients with progressive carcinoids of lung/thymus Pasireotide 60 mg/month IM (n=41) PD Key patient inclusion criteria Metastatic RECIST progressive carcinoids of lung/thymus (n=124) Everolimus 10 mg/day PO (n=42) R 1:1:1 PD Pasireotide 60 mg/month + everolimus 10 mg/day (n=41) PD Primary endpoint PFR at 9 months Secondary endpoints PFS, DCR, safety Ferolla et al. Ann Oncol 2016; 27 (suppl 6): abstr 416O

Pasireotide + everolimus 416O: Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Results from the randomized, phase 2 LUNA study – Ferolla P, et al Key results Progression-free rate at 9 months was: pasireotide 39.0% (95%CI 24.2, 55.5); everolimus 33.3% (95%CI 19.6, 49.5); pasireotide + everolimus 58.5% (95%CI 42.1, 73.7) Most common AEs in the pasireotide + everolimus arm were: hyperglycaemia (88%), diarrhoea (78%), weight decrease (56%), asthenia (37%), and stomatitis (34%) Conclusions In the treatment of advanced lung/thymus carcinoids, promising 9-month PFR was seen in all treatment arms, and particularly in the combination arm No new safety signals were observed for pasireotide or everolimus Best overall response (9-month) Pasireotide Everolimus Pasireotide + everolimus CR, % PR, % 2 SD, % 34 31 49 PD, % 17 Not assessed, % 44 60 42 Ferolla et al. Ann Oncol 2016; 27 (suppl 6): abstr 416O