2. 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 This slide set specifically focuses on the ESMO 2018 Congress and is available in 4 languages – English, French, Chinese and Japanese. 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 I would like to thank our ETOP members 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. Finally, we are also very grateful to Lilly Oncology for their financial, administrative and logistical support in the realisation of this activity. Yours sincerely, Rolf Stahel President, ETOP Foundation Council

3. ETOP Medical Oncology Slide Deck Editors 2018
Focus: advanced NSCLC (not radically treatable stage III & stage IV)
Dr Solange Peters
Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland
Focus: other malignancies, SCLC, mesothelioma, rare tumours
Dr Martin Reck
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany

4. Contents
Screening and biomarkers
Early stage and locally advanced NSCLC – Stages I, II and III
Advanced NSCLC – Not radically treatable stage III and stage IV
First line
Later lines
Other malignancies
SCLC, mesothelioma and thymic epithelial tumours

5. Screening and biomarkers

6. 65PD: High tumor mutational burden (TMB) and PD-L1 have similar predictive utility in 2L+ NSCLC patients (pts) treated with anti-PD-L1 and anti-CTLA-4 – Higgs BW, et al
Study objective
To compare the utility of high TMB and PD-L1 to predict outcomes in patients with non-squamous NSCLC who were treated with durvalumab and tremelimumab
Methods
Immunotherapy-naïve patients (n=213) with non-squamous EGFR and ALK wild- type NSCLC who had progressed after one prior platinum-based therapy were enrolled to durvalumab 20 mg/kg q4w for up to 12 months with tremelimumab 1 mg/kg q4w for 4 cycles
Tumour PD-L1 expression classified as ≥25% or <25% using the Ventana PD-L1 (SP263) assay
DNA sequencing was performed on 106 of 200 (53%) available tumour biopsies and TMB high defined as the top tertile of values (11 mut/Mb)
Higgs BW, et al. Ann Oncol 2018;29(suppl 5):Abstr 65PD

7. There was no appreciable correlation between TMB and PD-L1
65PD: High tumor mutational burden (TMB) and PD-L1 have similar predictive utility in 2L+ NSCLC patients (pts) treated with anti-PD-L1 and anti-CTLA-4 – Higgs BW, et al
Key results
There was no appreciable correlation between TMB and PD-L1
Low linear correlation between PD-L1 levels and TMB
PD-L1 vs. TMB status overlap
PD-L1 ≥25%
n=16
16%
TMB high
n=17
17%
n=18
PD-L1 TC, %
TMB, mutations/Mb 30 40 50 60 70 80 90
100 20 10 5 25 35 55 45 15
rho=0.3
PD-L1 <25%/ TMB low
n=52 50%
Higgs BW, et al. Ann Oncol 2018;29(suppl 5):Abstr 65PD

8. Patients who were TMB high (≥11 mut/Mb) had improved ORR, PFS and OS
65PD: High tumor mutational burden (TMB) and PD-L1 have similar predictive utility in 2L+ NSCLC patients (pts) treated with anti-PD-L1 and anti-CTLA-4 – Higgs BW, et al
Key results
Conclusions
In this study of patients with non-squamous NSCLC TMB and PD-L1 expression were not correlated
Patients who were TMB high (≥11 mut/Mb) had improved ORR, PFS and OS
TMB ≥11 mut/Mb (n=37)
TMB <11 mut/Mb (n=69)
PD-L1 ≥25% (n=57)
PD-L1 <25% (n=136)
Total*
(N=213)
PFS
Median, months (95%CI)
7.1 (1.7, 9.1)
1.7 (1.6, 3.6)
7.1 (3.5, 9.2)
3.3 (1.7, 3.6)
3.5 (1.8, 4.0)
12-month PFS, % (95%CI)
26.8 (13.8, 41.6)
12.6 (5.6, 22.6)
34.2 (21.9, 46.8)
10.0 (4.8, 17.5)
17.6 (12.4, 23.6) OS
NE (7.9, NE)
8.9 (4.8, NE)
15.5 (15.4, NE)
9.5 (6.7, NE)
15.4 (10.0, NE)
12-month OS, % (95%CI)
61.2 (42.4, 75.5)
43.0 (30.4, 55.0)
71.6 (57.3, 81.9)
47.3 (38.2, 55.9)
53.8 (46.4, 60.6)
*20 patients had unknown PD-L1 expression; NE, not estimable
Higgs BW, et al. Ann Oncol 2018;29(suppl 5):Abstr 65PD

9. 1136PD: Discrepancy of tumor neoantigen burden between primary lesions and matched metastases in lung cancer – Jiang T, et al
Study objective
To compare neoantigen landscapes in primary tumours and metastases in patients with lung cancer
Key result
Conclusion
Neoantigen landscapes were similar in primary tumours and metastases, however, only 20% of neoantigens were shared
Comparison of neoantigens in primary tumours and metastases by baseline characteristics
Primary
Female
Yes
SCLC
Metastasis
Male No
LUAD
Neoantigen counts
Age, years
Gender
Smoking
Histology
LM15
LM18
LM21
LM14
LM10
LM08
LM13
LM16
LM11
LM19
BM12
BM14
BM18
BM15
Gender
Smoking
Histology
LUSC
Jiang T, et al. Ann Oncol 2018;29(suppl 5):Abstr 1136PD

10. Early stage and locally advanced NSCLC – Stages I, II and III

11. LBA48_PR: CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-adjuvant treatment for stage IIIA–N2 EGFR-mutation non-small-cell lung cancer (EMERGING): a randomised study – Zhong W, et al
Study objective
To investigate the efficacy of erlotinib vs. gemcitabine + cisplatin as neoadjuvant/ adjuvant treatment in patients with locally advanced EGFR mutant NSCLC
Erlotinib 150 mg/day for 42 days
(n=37)
Erlotinib 150 mg/day for 12 months
Non-PD
Key patient inclusion criteria
Treatment naïve IIIA-N2 NSCLC
EGFR activating mutation
ECOG PS 0–1
(n=72)
SURGERY
Stratification
Lymph node status
Histology
Smoking
Sex R
1:1
Gemcitabine + cisplatin* q3w for 2 cycles
(n=35)
Gemcitabine + cisplatin* q3w for 2 cycles
Primary endpoint
ORR
Secondary endpoints
Downstaging rates of pathological lymph nodes, pCR, PFS, OS, safety
*Gemcitabine 1250 mg/m2 D1, 8; cisplatin 75 mg/m2 D1
Zhong W, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA48_PR

12. Gemcitabine + cisplatin (n=35)
LBA48_PR: CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-adjuvant treatment for stage IIIA–N2 EGFR-mutation non-small-cell lung cancer (EMERGING): a randomised study – Zhong W, et al
Key results
ORR in the ITT population was 54.1% (95%CI 37.2, 70.9) with erlotinib vs % (95%CI 17.7, 50.8) with gemcitabine + cisplatin (OR 2.26 [95%CI 0.87, 5.84], p=0.092)
Erlotinib
(n=37)
Gemcitabine + cisplatin (n=35)
p-value
Surgery, n (%)
31 (83.8)
24 (68.6)
0.129
Complete resection, n (%) R0 R1 R2
27 (73.0) 27 (73.0) 1 (2.7) 3 (8.1)
22 (62.9) 22 (62.9) 1 (2.9) 1 (2.9)
0.358
Lymph node downstage, n (%) N2pN0 N2pN1 N2pN2
4 (10.8) 3 (8.1) 1 (2.7) 27 (73.0)
1 (2.9) 1 (2.9) 0 (0) 23 (65.7)
0.185
Zhong W, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA48_PR

13. Progression-free survival, %
LBA48_PR: CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-adjuvant treatment for stage IIIA–N2 EGFR-mutation non-small-cell lung cancer (EMERGING): a randomised study – Zhong W, et al
Key results
Conclusion
Erlotinib in the neoadjuvant setting for EGFRm NSCLC improved ORR, MPR, R0 resection and lymph node downstaging and the safety profile was in line with previous reports
PFS (ITT population)
100 80 60 40 20
Progression-free survival, % 37 35 6 28 12 21 13 18 16 4 24 7 3 30 2 1 36 42
Time, months
76.7%
49.0%
36.4%
14.4%
Group
Events
mPFS, months (95%CI)
Erlotinib (n=37) 20
21.5 (19.3, 23.6)
Gemcitabine + cisplatin (n=35) 26
11.9 (9.1, 14.7)
HR 0.42 (95%CI 0.23, 0.76), p=0.003
No.at risk
Erlotinib
Gemcitabine
+ cisplatin
Zhong W, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA48_PR

14. Ipilimumab 1 mg/kg D1 + nivolumab 3 mg/kg D1, 15, 29 (n=18)
LBA49: Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC) – Cascone T, et al
Study objective
To investigate the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with untreated resectable NSCLC
Nivolumab 3 mg/kg D 1, 15, 29
(n=18)
Adjuvant therapy
Surgery
Key patient inclusion criteria
Stage I–IIIA NSCLC
Eligible for surgery
(n=44)
Stratification
Stage R
1:1
Ipilimumab 1 mg/kg D1 + nivolumab 3 mg/kg D1, 15, 29 (n=18)
Adjuvant therapy
Surgery
Primary endpoint
Major pathological response (MPR)
Secondary endpoints
Safety, perioperative mortality and morbidity, ORR, RFS, OS, complete resection rate, pCR
Cascone T, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA49

15. Nivolumab + ipilimumab
LBA49: Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC) – Cascone T, et al
Key results
Total
Nivolumab
Nivolumab + ipilimumab
Evaluable (resected)
n=26
n=14
n=12
MPR + pCR, n (%)
8 (31)
4 (28)
4 (33)
0% viable tumour cells (pCR), n (%)
5 (19)
2 (14)
3 (25)
1–10% viable tumour cells, n (%)
3 (11)
1 (8)
Overall (resected + unresectable)
n=31
n=16
n=15
8 (26)
4 (25)
4 (27)
5 (16)
2 (13)
3 (20)
3 (10)
1 (7)
Cascone T, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA49

16. Nivolumab + ipilimumab (n=16)
LBA49: Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC) – Cascone T, et al
Key results (cont.)
Conclusions
In resected patients with NSCLC, neoadjuvant nivolumab or nivolumab + ipilimumab induced an MPR rate of 31%
Greater TIL proliferation and activation was demonstrated with neoadjuvant nivolumab and nivolumab + ipilimumab compared with untreated tumours
Radiographic responses
Evaluable
Total (n=32)
Nivolumab (n=16)
Nivolumab + ipilimumab (n=16)
Response, n (%) CR PR SD PD
1 (3)
6 (19)
19 (59)
0 (0)
5 (31)
8 (50)
3 (19)
1 (6)
11 (69)
ORR, n/N (%)
7/32 (22)
5/16 (31)
2/16 (12)
Nivolumab (evaluable) (n=16)
Nivolumab + ipilimumab (evaluable) (n=16) 35 * 21 14 22 13 14 12 7 4 10 3 2 4
Overall % change in tumour size from baseline –2 –6
–12
–16
–17
–18 *
–19
–20
–30
–21
–34
–31
–39
–39
–45
–100
*Considered SD in target lesion but overall PD due to new radiographic lesions
Cascone T, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA49

17. 1363O: Efficacy and safety evaluation based on time from completion of radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC – Faivre-Finn C, et al
Study objective
To investigate the efficacy and safety outcomes of durvalumab in the PACIFIC trial based on PD-L1 expression and the components of chemoradiation received prior to durvalumab or placebo
Key patient inclusion criteria
Stage III NSCLC
No progression after ≥2 cycles of platinum-CRT
Pre-cCRT tumour tissue for PD-L1 testing if available
WHO PS 0–1
(n=713)
Durvalumab 10 mg/kg q2w
(n=476)
Stratification
Age
Sex
Smoking history R
1:1
Placebo q2w
(n=237)
Primary endpoints
PFS by BICR, OS
Secondary endpoints
ORR, DoR and TTDM by BICR, PFS2 by investigator, safety, PROs
Faivre-Finn C, et al. Ann Oncol 2018;29(suppl 5):Abstr 1363O

18. 1363O: Efficacy and safety evaluation based on time from completion of radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC – Faivre-Finn C, et al
Key results
Median OS in the PD-L1 TC ≥1% was NR (95%CI NR, NR) with durvalumab and 29.1 months (95%CI 17.7, NR) for placebo; HR 0.53 (95%CI 0.36, 0.77)
Median OS in the PD-L1 TC <1% was NR (95%CI 20.8, NR) with durvalumab and NR (95%CI 27.3, NR) for placebo; HR 1.36 (95%CI 0.79, 2.34)
PFS (BICR) by PD-L1 TC ≥1%
PFS (BICR) by PD-L1 TC <1%
Events/ patients (%)
Median PFS, months (95%CI)
Durvalumab
84/212 (39.6)
17.8 (16.9, NR)
Placebo
59/91 (64.8)
5.6 (3.6, 11.0)
HR 0.46 (95%CI 0.33, 0.64)
Events/ patients (%)
Median PFS, months (95%CI)
Durvalumab
49/90 (54.4)
10.7 (7.3, NR)
Placebo
40/58 (69.0)
5.6 (3.7, 10.6)
HR 0.73 (95%CI 0.48, 1.11)
Probability of PFS
1.0
0.8
0.6
0.4
0.2
0.0 3 6 9 12 15 21 24 27 18
Time from randomisation, months
212 91
174 59
143 39
127 34 82 20 52 13 14 4 1 30 8
No. at risk
Durvalumab
Placebo
Probability of PFS
1.0
0.8
0.6
0.4
0.2
0.0 3 6 9 12 15 21 24 27 18
Time from randomisation, months 90 58 70 45 51 25 42 23 14 8 1 4 5
No. at risk
Durvalumab
Placebo
Faivre-Finn C, et al. Ann Oncol 2018;29(suppl 5):Abstr 1363O

19. 1363O: Efficacy and safety evaluation based on time from completion of radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC – Faivre-Finn C, et al
Key results (cont.)
Conclusions
Durvalumab led to improvement in PFS and OS in the PD-L1 ≥1% subgroup and PFS in the <1% PD-L1 subgroup
Durvalumab improved PFS and OS regardless of chemoradiation received prior to therapy
PFS (BICR)
Events / patients (%)
HR (95%CI)
Durvalumab
Placebo
Induction chemotherapy
Yes No
59/123 (48.0)
155/353 (43.9)
49/68 (72.1)
108/169 (63.9)
Platinum
Cisplatin
Carboplatin
115/266 (43.2)
91/199 (45.7)
87/129 (67.4)
65/102 (63.7)
Taxane
97/207 (46.9)
117/269 (43.5)
72/112 (64.3)
85/125 (68.0)
Etoposide
49/117 (41.9)
165/359 (46.0)
34/52 (65.4)
123/185 (66.5)
Vinorelbine
58/124 (46.8)
156/352 (44.3)
42/59 (71.2)
115/178 (64.6)
Dose of radiotherapy
<60 Gy
60–66 Gy
>66 Gy
16/38 (42.1)
187/407 (45.9)
10/30 (33.3)
11/15 (73.3)
130/202 (64.4)
15/19 (78.9)
0.25
0.5 1 2
Placebo better
Durvalumab better
Faivre-Finn C, et al. Ann Oncol 2018;29(suppl 5):Abstr 1363O

20. Chemotherapy: topotecan (oral or IV) q3w or carboplatin-etoposide q3w*
1664O: A randomized non-comparative phase II study of anti–PD-L1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: results from the IFCT-1603 Trial – Pujol J, et al
Study objective
To investigate the activity of atezolizumab as systemic therapy in patients with SCLC who have progressed after 1L platinum-based chemotherapy
Atezolizumab 1200 mg q3w
(n=49) PD
Key patient inclusion criteria
ED or LD SCLC
Progressive disease after 1L chemotherapy
No brain metastases
PS 0–2
(n=73)
Stratification
Sensitive vs. refractory disease
PS (0–1 vs. 2)
Limited vs. extensive disease
Gender R
2:1
Chemotherapy: topotecan (oral or IV) q3w or carboplatin-etoposide q3w*
(n=24) PD
Primary endpoint
ORR at 6 weeks (investigator assessed)
*Maximum 6 cycles
Pujol J, et al. Ann Oncol 2018;29(suppl 5):Abstr 1664O

21. Progression, n (%) [95%CI] 30 (69.8) [56.0, 83.5] 6 (30) [9.9, 50.1]
1664O: A randomized non-comparative phase II study of anti–PD-L1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: results from the IFCT-1603 Trial – Pujol J, et al
Key results
Atezolizumab (n=43)
Chemotherapy (n=20)
Total (n=64)
ORR at 6 weeks, n (%) [95%CI]
1 (2.3)
[0.0, 6.8]
2 (10)
[0.0, 23.1]
3 (4.8)
[0.0, 9.9]
DCR, n (%) [95%CI]
9 (20.9)
[8.8, 33.1]
13 (65)
[44.1, 85.9]
22 (34.9)
[23.1, 46.7]
Progression, n (%) [95%CI]
30 (69.8)
[56.0, 83.5]
6 (30)
[9.9, 50.1]
36 (57.1)
[44.9, 69.4]
Not done/not evaluable, n (%) [95%CI]
4 (9.3)
[0.6, 18.0]
1 (5.0)
[0.0, 14.6]
5 (7.9)
[1.3, 14.6]
Pujol J, et al. Ann Oncol 2018;29(suppl 5):Abstr 1664O

22. Progression-free survival
1664O: A randomized non-comparative phase II study of anti–PD-L1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: results from the IFCT-1603 Trial – Pujol J, et al
Key results (cont.)
Conclusions
In pre-treated patients with progressive SCLC, the efficacy of atezolizumab was inferior to chemotherapy
ORR at 6 weeks with atezolizumab monotherapy was 2.3% and median PFS was 1.4 months
Therefore, the planned phase 3 portion of the study was not activated
PFS (ITT population)
Median PFS, months (95%CI)
1.0
Chemotherapy (n=24): 4.3 (1.5, 5.9); 21 events, 3 censored
Atezolizumab (n=49): 1.4 (1.2, 1.5); 46 events, 3 censored
0.8
Median follow-up: 13.7 months (95%CI 12.7, NR)
0.6
HR (adjusted) atezolizumab group = 2.26 (95%CI 1.30, 3.93); p=0.004
Progression-free survival
0.4
6-month PFS rate for atezolizumab group: 6.3% [0.0, 13.1]
0.2 1 2 3 4 5 6 7 8 9
Time, months
Pujol J, et al. Ann Oncol 2018;29(suppl 5):Abstr 1664O

23. Advanced NSCLC Not radically treatable stage III and stage IV
First line

24. LBA10: Primary results of ALESIA: A randomised, phase III, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC – Zhou C, et al
Study objective
To investigate safety and efficacy of 1L alectinib vs. crizotinib in Asian patients with ALK+ NSCLC in the ALESIA study
Key patient inclusion criteria
Asian patients with stage IIIB/IV ALK+ NSCLC
Treatment naïve
ECOG PS 0–2
(n=187)
Alectinib 600 mg bid
(n=125)
Stratification
ECOG PS (0/1 vs. 2)
Baseline brain metastases R
2:1
Crizotinib 250 mg bid
(n=62)
Primary endpoint
PFS (investigator-assessed)
Secondary endpoints
PFS by IRC, time to CNS progression, ORR and DoR (investigator-assessed), OS, CNS ORR, safety, QoL, PK
Zhou C, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA10

25. LBA10: Primary results of ALESIA: A randomised, phase III, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC – Zhou C, et al
Key result
PFS (investigator-assessed)
Time to CNS progression (IRC-assessed)
Progression-free survival, %
Time, months
100 80 60 40 20 3 6 9 12 15 18 21
Alectinib
Crizotinib NE
11.1 months
Cumulative incidence*, %
Time, months 60 40 20 3 6 9 12 15 18 21
Alectinib
Crizotinib
7.3%
35.5% (95%CI 23.5, 47.8)
(95%CI 3.6, 12.8)
Alectinib (n=125)
Crizotinib (n=62)
Patients with event, n (%)
26 (20.8)
37 (59.7)
Median PFS, months (95%CI)
NE (20.3, NE)
11.1 (9.1, 13.0)
HR (95%CI); p-value (log-rank test)
0.22 (0.13, 0.38); p<0.0001
Cause-specific HR
p-value (log-rank test)
0.14 (95%CI 0.06, 0.30)
<0.0001
*Cumulative incidence of CNS progression without prior non-CNS progression or death
Zhou C, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA10

26. LBA10: Primary results of ALESIA: A randomised, phase III, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC – Zhou C, et al
Key result (cont.)
Conclusions
Alectinib led to a significant improvement in PFS and showed benefits in regards to ORR, DoR and time to CNS progression compared with crizotinib
The safety profile of alectinib in Asian patients was consistent with the previous findings
DoR (investigator-assessed)
Response, n (%)
Alectinib (n=125)
Crizotinib (n=62)
ORR
114 (91.2)
48 (77.4) CR
5 (4.0)
3 (4.8) PR
109 (87.2)
45 (72.6) SD
7 (5.6)
8 (12.9) PD
2 (1.6)
4 (6.5)
Missing or unevaluable
2 (3.2)
DoR (unconfirmed) ,%
Time, months
100 80 60 40 20 3 6 9 12 15 18 21
Alectinib
Crizotinib NE
9.3 months
Alectinib (n=114)
Crizotinib (n=48)
Median DoR, months (95%CI)
NE (18.4, NE)
9.3 (7.4, NE)
HR (95%CI), p-value (log-rank test)
0.22 (0.12, 0.40); p<0.0001
Zhou C, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA10

27. NGS was conducted using the Guardant360 assay or GuardantOMNI assay
LBA50: Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study – Ramalingam SS, et al
Study objective
To investigate the mechanisms of acquired resistance to osimertinib and standard of care (gefitinib + erlotinib) in patients who progressed or discontinued treatment in the FLAURA study
Methods
Patients in the FLAURA study had EGFR+ (ex19del or L858R) locally advanced or metastatic NSCLC and were treated with osimertinib or gefitinib + erlotinib until progression
Paired plasma samples were taken from patients at baseline and at progression/discontinuation for ctDNA genomic profiling
NGS was conducted using the Guardant360 assay or GuardantOMNI assay
Analysis set of valid paired NGS data were available for 272 patients
Osimertinib: 113/279 (41%)
Gefitinib + erlotinib: 159/277 (57%)
Ramalingam SS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA50

28. LBA50: Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study – Ramalingam SS, et al
Key results
The most common acquired resistance mechanisms in the osimertinib arm (n=91) were:
MET amplification (15%) and EGFR C797S mutation (7%)
There was no evidence of acquired T790M
The most common acquired resistance mechanisms in the gefitinib + erlotinib arm (n=129) were:
T790M (47%), MET amplification (4%) and HER2 amplification (2%)
Conclusions
There was no evidence of acquired resistance through T790M in the osimertinib-treated patients, while MET amplification and EGFR C797S mutations were the most common
New mechanisms that may lead to aggressive disease biology were not identified
Ramalingam SS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA50

29. NGS was undertaken using the Guardant360 assay
LBA51: Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study – Papadimitrakopoulou VA, et al
Study objective
To investigate the mechanisms of acquired resistance to osimertinib in patients who progressed or discontinued treatment in the AURA3 study
Methods
Patients in the AURA3 study had T790M+ locally advanced or metastatic NSCLC and were treated with osimertinib or platinum-pemetrexed until progression
Paired plasma samples were taken from patients at baseline and at progression/discontinuation for ctDNA genomic profiling
NGS was undertaken using the Guardant360 assay
Analysis set of valid paired NGS data were available for 113 patients
Osimertinib: 83/279 (30%)
Platinum-pemetrexed: 30/140 (21%)
Papadimitrakopoulou VA, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA51

30. Loss of T790M was seen in 49% of patients
LBA51: Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study – Papadimitrakopoulou VA, et al
Key results
Loss of T790M was seen in 49% of patients
Acquired EGFR mutations were observed in 21% of patients; the most common was C797S (14%)
Other mutations included: MET amplification (19%); cell cycle gene alterations (12%); HER2 amplification (5%); PIK3CA amplification/mutation (5%); oncogenic fusion (4%), BRAF V600E (3%)
All cases of C797X mutations were in the cis position when co-occurring with T790M
Conclusion
EGFR mutations and MET amplifications were the most common acquired resistance mechanisms to osimertinib among a diverse mixture, consistent with previous reports
Acquired EGFR mutations with osimertinib (represents 21% of total patients)
C797X: 15% (10 C797S, 1 C797G)
L792H/F
+ C797S: 1%
L792H: 1%
G796S: 1%
L718Q: 1%
Ex20ins: 1%
Papadimitrakopoulou VA, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA51

31. LBA52: Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC) – Wolf J, et al
Study objective
To investigate the efficacy and safety of capmatinib, a selective MET inhibitor, in patients with METΔex14 mutated advanced NSCLC
Cohort 4: Previously treated (1–2 prior lines) for advanced stage
Capmatinib 400 mg bid
(n=69)
Key patient inclusion criteria
Stage IIIB/IV NSCLC
METΔex14 determined centrally
EGFR wt and ALK negative
≥1 measureable lesion
ECOG PS 0–1
Cohort 5b: Treatment-naïve for advanced stage
Capmatinib 400 mg bid
(n=28)
Primary endpoint
ORR by BIRC
Secondary endpoints
DoR by BIRC
Wolf J, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA52

32. Cohort 5b (treatment naïve)
LBA52: Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC) – Wolf J, et al
Key results
ORR (BIRC) in Cohort 4 (pre-treated) was 39.1% (95%CI 27.6, 51.6)
ORR (BIRC) in Cohort 5b (treatment naïve) was 72.0% (95%CI 50.6, 87.9)
n=60†/69 *
Cohort 4 (pre-treated)
Best % change from baseline
Cohort 5b (treatment naïve) *
–25
–50
–75
–100
n=24†/25 PR SD PD NE
Best % change from baseline
*Patients still on treatment; †number of patients with measurable disease at baseline and ≥1 post-baseline assessment
Wolf J, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA52

33. Cohort 5b (treatment naive)
LBA52: Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC) – Wolf J, et al
Key results
Conclusions
In patients with METΔex14 advanced NSCLC, capmatinib shows promising results
The differential benefit of 1L over later-line treatment highlights the need for prompt targeted treatment in this patient group
AE, n (%)
Cohort 4 (pre-treated)
(n=69)
Cohort 5b (treatment naive)
(n=28)
All patients
(N=302)
All grades
Grade 3/4
Any
60 (87.0)
33 (47.8)
27 (96.4)
14 (50.0)
253 (83.8)
100 (33.1)
Peripheral oedema
31 (44.9)
10 (14.5)
18 (64.3)
1 (3.6)
122 (40.4)
19 (6.3)
Nausea
24 (34.8)
11 (39.3)
99 (32.8)
5 (1.7)
Vomiting
13 (18.8)
4 (14.3)
58 (19.2)
6 (2.0)
Blood creatinine increased
15 (21.7)
7 (25.0)
Fatigue
9 (13.0)
4 (5.8)
2 (7.1)
40 (13.2)
10 (3.3)
Decreased appetite
1 (1.4)
5 (17.9)
3 (1.0)
Diarrhoea
8 (11.6)
3 (10.7)
35 (11.6)
Wolf J, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA52

34. Induction treatment (4 or 6 cycles) Maintenance treatment
LBA53: IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC – Cappuzzo F, et al
Study objective
To investigate the efficacy and safety of atezolizumab combined with carboplatin + nab-paclitaxel vs. carboplatin + nab-paclitaxel in chemotherapy-naïve patients with stage IV non-squamous NSCLC
Induction treatment (4 or 6 cycles)
Maintenance treatment
Atezolizumab 1200 mg q3w + carboplatin AUC 6 q3w + nab-paclitaxel 100 mg/m2 q3w
Loss of clinical benefit/toxicity
Key patient inclusion criteria
Stage IV non-squamous NSCLC
Chemotherapy-naïve
Pre-treated EGFR mutated or ALK translocation (TKI)
(n=723; ITT-WT* n=679)
Atezolizumab
Stratification
Sex
Baseline liver metastases
PD-L1 tumour expression R
2:1
Carboplatin AUC 6 q3w + nab-paclitaxel 100 mg/m2 q3w
PD/ toxicity
Best supportive care or pemetrexed q3w
Co-primary endpoints
Investigator-assessed PFS and OS (ITT-WT* population)
Secondary endpoints
OS and PFS (ITT population and by PD-L1 expression), ORR, safety
*ITT-WT population, randomised patients excluding those with EGFR or ALK mutations
Cappuzzo F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA53

35. Investigator-assessed PFS (ITT-WT)
LBA53: IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC – Cappuzzo F, et al
Key results
Investigator-assessed PFS (ITT-WT)
OS (ITT-WT)
PFS, %
Months after randomisation
1.0
0.8
0.6
0.4
0.2
0.0
451
228 1
432
214 2
383
174 3
351
150 4
329
136 5
281
110 30
No. at risk
Atezo + CnP
Chemo 6
242 90 7
213 75 8
183 61 9
157 48 10
138 40 11
132 35 12
119 29 13
108 23 14 83 18 15 78 16 62 17 60 41 19 36 20 21 22 24 25 26 27 28
1.0
PFS rate, %
6-month
12-month
Atezolizumab + CnP
56.1
29.1
CnP
42.5
14.1
0.8
OS rate, %
1-year
2-year
Atezolizumab + CnP
63.1
39.6
CnP
55.5
30.0
0.6
Median follow-up: ~19 months
HR 0.79
(95%CI 0.64, 0.98)
p=0.033
HR 0.64
(95%CI 0.54, 0.77)
p<0.0001
OS, %
0.4
0.2
Median: 5.5 mo (95%CI 4.4, 5.9)
Median: 7.0 mo (95%CI 6.2, 7.3)
0.0
Median: 13.9 mo (95%CI 12.0, 18.7)
Median: 18.6 mo (95%CI 16.0, 21.2)
451
228 1
435
218 2
422
206 3
400
190 4
384
176 5
365
167 6
351
161 7
333
154 8
315
147 9
305
136 10
294
132 11
284
124 12
268
119 13
253
109 14
217 96 15
194 90 16
167 75 17
147 65 18
129 58 19
103 49 20 88 39 21 75 31 2 22 59 24 32 1 23 17 33 24 40 13 34 25 29 9 26 19 8 27 12 3 28 10 1 6 30 4
Months after randomisation
No. at risk
Atezo + CnP
Chemo
Cappuzzo F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA53

36. PD-L1-negative TC0 and IC0
LBA53: IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC – Cappuzzo F, et al
Key results (cont.)
Conclusions
In the ITT-WT population atezolizumab + chemotherapy showed benefit in PFS and OS, which was maintained across all PD-L1 subgroups
No new safety signals were observed with the combination of atezolizumab + chemotherapy
PFS by baseline PD-L1 status (ITT-WT)
PFS, %
100 80 60 40 20 88 42 2 76 32 4 64 23
No. at risk
Atezo+CnP
Chemo 6 43 18 8 34 11 10 28 9 12 22 14 17 1 16 24 3 26
PD-L1-high TC3 or IC3
Time, months 30
PD-L1-low TC1/2 or IC1/2
PFS, %
100 80 60 40 20
128 65 2
113 49 4
103 42 6 83 8 64 10 51 12 9 14 28 5 16 3 18 1 22 24 26
Time, months 30
PD-L1-negative TC0 and IC0
PFS, %
100 80 60 40 20
235
121 2
194 93 4
162 71 6
116 42 8 85 10 59 19 12 55 16 14 38 9 34 18 24 17 3 22 5 1 26 28
Time, months
Atezo + CnP
(n=88)
CnP
(n=42)
Median PFS,
mo (95%CI)
6.4 (5.49, 9.76)
4.6 (3.22, 7)
HR (95%CI)
0.51 (0.34, 0.77)
Atezo + CnP
(n=128)
CnP
(n=65)
Median PFS,
mo (95%CI)
8.3 (7.16, 10.35)
6.0 (5.29, 6.93)
HR (95%CI)
0.61 (0.43, 0.85)
Atezo + CnP
(n=235)
CnP
(n=121)
Median PFS,
mo (95%CI)
6.2 (5.52, 7.16)
4.7 (4.11, 5.72)
HR (95%CI)
0.72 (0.56, 0.91)
Cappuzzo F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA53

37. LBA54: IMpower132: efficacy of atezolizumab (atezo) + carboplatin (carbo)/cisplatin (cis) + pemetrexed (pem) as 1L treatment in key subgroups with stage IV non-squamous non-small cell lung cancer (NSCLC) – Barlesi F, et al
Study objective
To investigate the PFS benefit of atezolizumab combined with carboplatin or cisplatin + pemetrexed in patients from IMpower132 in an exploratory analysis stratified by race, age, smoking history or liver metastasis at baseline
Induction therapy (4 or 6 cycles)
Maintenance therapy
Atezolizumab + carboplatin or cisplatin + pemetrexed*
PD/ loss of clinical benefit
Atezolizumab + pemetrexed*
Key patient inclusion criteria
Stage IV non-squamous NSCLC
Chemotherapy-naïve
Without EGFR or ALK genetic alteration
(n=578)
Stratification
Sex
Smoking status
ECOG PS
Chemotherapy regimen R
1:1
Carboplatin or cisplatin + pemetrexed*
PD/ loss of clinical benefit
Pemetrexed*
Exploratory endpoints
Clinical and biomarker subgroup analysis
*Atezolizumab 1200 mg IV q3w; carboplatin AUC 6 mg/mL/min IV q3w; cisplatin 75 mg/m2 IV q3w; pemetrexed 500 mg/m2 IV q3w
Barlesi F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA54

38. Former/current smokers
LBA54: IMpower132: efficacy of atezolizumab (atezo) + carboplatin (carbo)/cisplatin (cis) + pemetrexed (pem) as 1L treatment in key subgroups with stage IV non-squamous non-small cell lung cancer (NSCLC) – Barlesi F, et al
Key results
Conclusion
Atezolizumab added to carboplatin/cisplatin + pemetrexed improved PFS across several subgroups including patients from Asia, never smokers, those who were older and those without liver metastases at baseline, but currently has not shown improvement in OS
PFS, %
Time, months
1.0
0.8
0.6
0.4
0.2
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 20 19 21 22
Median PFS (95%CI), mos
HR (95%CI)
Non-Asian patients
Atezolizumab + PP
6.9 (5.9, 8.1) PP
5.0 (4.2, 5.7)
0.65 (0.53, 0.81)
Atezolizumab + PP (n=221)
PP (n=221)
Asian patients
10.2 (8.3, 15.3)
5.3 (4.3, 6.7)
0.42 (0.28, 0.63)
Atezolizumab + PP (n=71)
PP (n=65)
PFS, %
Time, months
1.0
0.8
0.6
0.4
0.2
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 20 19 21 22
Median PFS (95%CI), mos
HR (95%CI)
Former/current smokers
Atezolizumab + PP
7.5 (6.3, 8.4) PP
5.1 (4.3, 5.6)
0.61 (0.50, 0.74)
Atezolizumab + PP (n=225)
PP (n=226)
Never smokers
8.6 (6.5, 15.4)
5.5 (4.0, 8.3)
0.49 (0.28, 0.87)
Atezolizumab + PP (n=37)
PP (n=30)
Barlesi F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA54

39. LBA55: Primary efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L nonsmall cell lung cancer (NSCLC) – Kim ES, et al
Study objective
To investigate the use of bTMB as a predictive biomarker for atezolizumab monotherapy in 1L NSCLC
Key patient inclusion criteria
Stage IIIB/IVA locally advanced or metastatic NSCLC
Immunotherapy naïve
PD-L1 unselected
ECOG PS 0–1
(n=152)
Atezolizumab 1200 mg q3w
(biomarker evaluable population n=119)
PD/toxicity/ loss of benefit
Co-primary endpoints
Investigator-assessed ORR and PFS (using pre-specified bTMB cut-off of 16)
Secondary endpoints
Safety, investigator-assessed DoR and OS
Kim ES, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA55

40. Overall response rate, %
LBA55: Primary efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L nonsmall cell lung cancer (NSCLC) – Kim ES, et al
Key results
ORR per RECIST v1.1
bTMB subgroups
Overall response rate, %
ITT
(N=152)
BEP
(n=119)
High
(n=49)
Low
(n=70)
(n=28)
(n=91)
(n=19)
(n=100) PR CR
≥10 cut-off
≥16 cut-off
≥20 cut-off
p<0.0001
p=0.0002
p=0.0595
Kim ES, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA55

41. PFS in bTMB high (≥16) vs. low (<16) subgroups
LBA55: Primary efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L nonsmall cell lung cancer (NSCLC) – Kim ES, et al
Key results (cont.)
Conclusion
In patients with NSCLC treated with atezolizumab monotherapy a numerical improvement in outcomes was seen in those with a bTMB cut-off of ≥16
PFS in bTMB high (≥16) vs. low (<16) subgroups
Progression-free survival, %
Time, months
100 80 60 40 20 28 91 1 27 86 2 17 56 3 14 43
No. at risk
High (≥16)
Low (<16)
High, ≥16 (n=28)
Low, <16 (n=91)
6-month PFS
41.6% vs. 32.8%
9-month PFS
37.4% vs. 9.7% 4 39 5 13 6 11 21 7 8 9 10 12
bTMB high (n=28)
bTMB low (n=91)
Median PFS, months (90%CI)
4.6 (1.6, 11.0)
3.7 (2.6, 4.3)
HR (90%CI)
0.66 (0.42, 1.02)
p-value
0.12
Kim ES, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA55

42. LBA58: Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the phase 3 ALTA-1L trial – Popat S, et al
Study objective
To investigate the intracranial efficacy of brigatinib vs. crizotinib in ALK inhibitor- naïve patients with advanced ALK+ NSCLC in the ATLA-1L study
Key patient inclusion criteria
Stage IIIb/IV NSCLC
ALK+ (based on local ALK testing)
No prior ALK inhibitor
≤1 prior systemic therapy
Brain metastases were allowed
(n=275)
Brigatinib 180 mg/day (90 mg/day for 7 day lead-in)
(n=137)
PD/toxicity/ discontinuation
Stratification
Brain metastases at baseline
Prior chemotherapy R
1:1
Crizotinib 250 mg bid
(n=138)
PD*/toxicity/ discontinuation
Primary endpoint
PFS (BIRC-assessed)
Secondary endpoints
ORR, intracranial ORR, intracranial PFS, OS, safety
*Crossover to brigatinib permitted at PD
Popat S, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA58

43. LBA58: Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the phase 3 ALTA-1L trial – Popat S, et al
Key results
Conclusion
In patients with advanced ALK+ NSCLC, brigatinib demonstrated superior intracranial efficacy vs. crizotinib, with significantly higher intracranial response and improved intracranial PFS in those with brain metastases
Whole body BIRC-assessed PFS by brain metastases at baseline
With brain metastases
Without brain metastases
PFS, % of patients
Time, months
100 80 60 40 20 3 6 9 12 15 18
HR 0.20 (95%CI 0.09, 0.46)
p< by log-rank test
Brigatinib (n=40)
Crizotinib (n=41)
PFS, % of patients
Time, months
100 80 60 40 20 3 6 9 12 15 18
HR 0.72 (95%CI 0.44, 1.18)
p=0.20 by log-rank test
Brigatinib (n=97)
Crizotinib (n=97)
Treatment
Pts with events, n (%)
Median PFS, months (95%CI)
1-year PFS rate, % (95%CI)
Brigatinib (n=40)
8 (20) NR
75 (56, 87)
Crizotinib (n=41)
24 (59)
5.6 (3.8, 11.1)
25 (8, 46)
Treatment
Pts with events, n (%)
Median PFS, months (95%CI)
1-year PFS rate, % (95%CI)
Brigatinib (n=97)
28 (29) NR
63 (50, 74)
Crizotinib (n=41)
39 (40)
11.1 (9.2, NR)
49 (36, 61)
Popat S, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA58

44. Tepotinib 500 mg/day + gefitinib 250 mg/day
1377O: Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive (MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small lung cancer (NSCLC) – Wu Y, et al
Study objective
To investigate the efficacy and safety of tepotinib + gefitinib vs. chemotherapy in Asian patients with advanced MET+/EGFR+T790M- NSCLC
Tepotinib 500 mg/day + gefitinib 250 mg/day
(n=31)
Key patient inclusion criteria
Locally-advanced/metastatic IV NSCLC
EGFR+, T790M–, MET+
Asian
Resistance to prior EGFR TKI
No prior HGF/MET pathway-directed therapy
(n=55)
PD/ toxicity
Stratification
MET+ type (IHC2+, IHC3+ or MET amplification)
Prior EGFR-TKI therapy R*
Chemotherapy: Pemetrexed 500 mg/m2 q3w+ cisplatin 75 mg/m2 or carboplatin AUC 5 or 6 q3w
(n=24)
PD/ toxicity
Primary endpoint
PFS (investigator-assessed)
Secondary endpoints
ORR, safety
*Initially 1:1 and changed to 2:1 at protocol amendment (30 Sept 2016)
Wu Y, et al. Ann Oncol 2018;29(suppl 5):Abstr 1377O

45. Tepotinib + gefitinib (n=31)
1377O: Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive (MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small lung cancer (NSCLC) – Wu Y, et al
Key results
In the MET IHC3+ subgroup (n=34) median PFS was 8.3 months with tepotinib + gefitinib and 4.4 months with chemotherapy (HR 0.35 [95%CI 0.17, 0.74])
In the MET amplification subgroup (n=19) median PFS was 21.2 months with tepotinib + gefitinib and 4.2 months with chemotherapy (HR 0.17 [95%CI 0.05, 0.57])
Investigator-assessed PFS (ITT population)
Tepotinib + gefitinib (n=31)
Chemotherapy (n=24)
Events 23 19
Median PFS, months (90%CI)
4.9 (3.9, 6.9
4.4 (4.2, 6.8)
Stratified HR (90%CI)
0.71 (0.36, 1.39)
1.0
0.8
0.6
Tepotinib + gefitinib
Chemotherapy
KM estimate for PFS
0.4
0.2
0.0 31 24 3 20 16 6 11 7 12 1 18 1 24 30
No. at risk
Tep + gef
Chemo
Time, months
Wu Y, et al. Ann Oncol 2018;29(suppl 5):Abstr 1377O

46. 1377O: Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive (MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small lung cancer (NSCLC) – Wu Y, et al
Key results
Tepotinib + gefitinib was generally well tolerated, with TEAEs leading to discontinuation in 9.7% of patients compared with 4.3% in the chemotherapy group
Conclusion
In patients with advanced NSCLC and MET amplifications, improvements in PFS were observed with tepotinib + gefitinib, indicating that MET may be considered as a biomarker for treatment with tepotinib
Tepotinib + gefitinib
Chemotherapy
Odds ratio (90%CI)
Responders*
n/N
ORR, %
(90%CI)
Responders* n/N
ORR, % (90%CI)
Overall (n=55)
14/31
45.2 (29.7, 61.3)
8/24
33.3 (17.8, 52.1)
1.99 (0.56, 6.87)
MET IHC3+ (n=34)
13/19
68.4 (47.0, 85.3)
5/15
33.3 (14.2, 57.7)
4.33 (1.03, 18.33)
MET amplification (n=19)
8/12
66.7 (39.1, 87.7)
3/7
42.9 (12.9, 77.5)
2.67 (0.37, 19.56)
*No confirmation required
Wu Y, et al. Ann Oncol 2018;29(suppl 5):Abstr 1377O

47. 1379PD: Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study – Dziadziuszko R, et al
Study objective
To assess efficacy of alectinib vs. crizotinib in the ALEX trial in patients with ALK+ advanced NSCLC stratified by EML4-ALK fusion variants
Methods
FOUNDATIONACT and FOUNDATIONONE NGS platforms were used to determine the ALK fusion variants in plasma and tissue BEP subgroups
Alectinib 600 mg bid
Key patient inclusion criteria
ALK+ NSCLC
No prior treatment for NSCLC
ECOG PS 0–2
(n=303)
PD/death/ withdrawal R
1:1
Crizotinib 250 mg bid
PD/death/ withdrawal
Dziadziuszko R, et al. Ann Oncol 2018;29(suppl 5):Abstr 1379PD

48. PFS (investigator-assessed)
1379PD: Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study – Dziadziuszko R, et al
Key results
Conclusion
In patients with ALK+ NSCLC alectinib demonstrated greater efficacy than crizotinib, regardless of EML4-ALK variant
PFS (investigator-assessed)
Plasma BEP subgroup
Tissue BEP subgroup
Crizotinib
Alectinib
Crizotinib
Alectinib
EML4-ALK V1: 7.4
EML4-ALK V2: 8.8
EML4-ALK V3a/b: 9.1
Median PFS, months
Median PFS, months
EML4-ALK V1: 12.9
EML4-ALK V2: 8.8
EML4-ALK V3a/b: 14.6
Median PFS, months
Median PFS, months
EML4-ALK V1: NE
EML4-ALK V2: 14.9
EML4-ALK V3a/b: NE
EML4-ALK V1: NE
EML4-ALK V2: 11.5
EML4-ALK V3a/b: NE
1.0
1.0
1.0
1.0
0.8
0.8
0.8
0.8
0.6
0.6
0.6
0.6
Survival probability
0.4
0.4
0.4
0.4
0.2
0.2
0.2
0.2
0.0
0.0
0.0
0.0 3 6 9 12 15 18 21 24 3 6 9 12 15 18 21 24 27 30 3 6 9 12 15 18 21 24
Time, months 3 6 12 15 18 21 24 9 27 30
Time, months
Time, months
Time, months
ALK V1 ALK V2 ALK V3a/b
Dziadziuszko R, et al. Ann Oncol 2018;29(suppl 5):Abstr 1379PD

49. Molecular profiling of tumour tissue and blood was performed
1380PD: Efficacy of lorlatinib in patients (pts) with ROS1-positive advanced non-small cell lung cancer (NSCLC) and ROS1 kinase domain mutations – Solomon BJ, et al
Study objective
To investigate molecular profiling of patients with ROS1+ advanced NSCLC in the B study of lorlatinib
Methods
Patients with locally advanced or metastatic NSCLC with ROS1 rearrangements were enrolled in the phase 1/2 study
Patients were treatment-naïve in the advanced setting of PD after ≥1 prior ROS1 inhibitor (phase 1) or any number of prior therapies (phase 2)
Lorlatinib was orally administered in continuous 21-day cycles with escalating doses (10 mg/day to 100 mg bid) in phase 1 and 100 mg/day in phase 2
Molecular profiling of tumour tissue and blood was performed
All patients had tissue samples collected before enrolment and tissue collection was encouraged on PD; tumour tissue was analysed with a ROS1 kinase domain mutation- focused NGS panel
Blood samples were collected at screening, at the beginning of cycle 3, and at the end- of-treatment visit for circulating-free DNA (cfDNA) analysis using an NGS panel or digital PCR
Solomon BJ, et al. Ann Oncol 2018;29(suppl 5):Abstr 1380PD

50. ROS1 kinase domain mutations occurred in 10–14% of samples
1380PD: Efficacy of lorlatinib in patients (pts) with ROS1-positive advanced non-small cell lung cancer (NSCLC) and ROS1 kinase domain mutations – Solomon BJ, et al
Key results
Conclusions
ROS1 kinase domain mutations occurred in 10–14% of samples
In patients with ROS1 kinase domain resistance mutations, lorlatinib exhibited some anti-tumour activity
Percentage change in tumour size from baseline in patients with ≥1 ROS1 kinase domain mutation
ORR by presence of ROS1 mutations
Best percentage change from baseline
G2032R
Partial response
Stable disease
Progressive disease
Best overall response
ROS1 kinase domain mutation in:
cfDNA
Tumour tissue
Both cfDNA and tumour tissue
G2032R/
L2026M
S1986F
K1991E
ROS1 TKI-naïve (n=17)
Prior crizotinib (n=36)*
Prior non-crizotinib TKI or ≥2 TKIs (n=5)
No mutation (n=17)
≥1 mutation (n=0)
No mutation (n=27)
≥1 mutation (n=8)
No mutation (n=4)
≥1 mutation (n=1)
Best overall response, n (%) CR
2 (11.8) –
1 (3.7) PR
9 (52.9)
8 (29.6)
2 ( 25.0) SD
5 (29.4)
5 (62.5)
3 (75.0)
1 (100) PD
1 (5.9)
3 (11.1)
1 (12.5)
1 (25.0)
Indeterminate
7 (25.9)
Responders, n (%)
11 (64.7)
9 (33.3)
2 (25.0)
*One patient had a non-analysable or uninformative sample
Solomon BJ, et al. Ann Oncol 2018;29(suppl 5):Abstr 1380PD

51. Pemetrexed 500 mg/m2 q3w + gefitinib 250 mg/day (n=126)
1381PD Gefitinib with or without pemetrexed in nonsquamous non-small cell lung cancer with EGFR mutation: Final overall survival results from a randomized phase II study – Chih-Hsin Yang J, et al
Study objective
To investigate the efficacy and safety of pemetrexed + gefitinib vs. gefitinib in non-squamous NSCLC with EGFR mutations
Key patient inclusion criteria
Stage IV or recurrent non-squamous NSCLC
Activating EGFR mutations
East Asian ≥18 years (≥20 years in Japan and Taiwan)
No prior systemic therapy for stage IV or recurrent NSCLC
ECOG PS 0–1
(n=191)
Pemetrexed 500 mg/m2 q3w + gefitinib 250 mg/day (n=126) R
2:1
Gefitinib 250 mg/day
(n=65)
Primary endpoint
PFS
Secondary endpoints
OS, time to progressive disease, tumour response rates, DoR, QoL, biomarker analysis, safety
Chih-Hsin Yang J et al. Ann Oncol 2018;29(suppl 5):abstr 1381PD

52. Median PFS, months (95%CI)
1381PD Gefitinib with or without pemetrexed in nonsquamous non-small cell lung cancer with EGFR mutation: Final overall survival results from a randomized phase II study – Chih-Hsin Yang J, et al
Key results
36 (28.6%) patients had TEAEs in the pemetrexed + gefitinib group and 7 (10.8%) in gefitinib group
Conclusion
In patients with EGFR+ advanced NSCLC pemetrexed + gefitinib significantly prolonged PFS, with a numerically longer, but not statistically significant, improvement in OS OS
Updated PFS
Time, months
Probability
1.0
0.8
0.6
0.4
0.2
0.0
126 65 6
118 64 12
106 53 18 92 45 24 79 36 30 66 27 58 26 42 51 19 48 43 15 54 8 60 3 2 1 72
No.at risk
P+G G
Median OS, months (95%CI)
43.4 months (33.4, 50.8)
36.8 months (26.7, 42.6)
Pemetrexed + gefitinib
Gefitinib
Adjusted HR 0.77 (95%CI 0.5, 1.2)
1-sided p=0.105
Time, months
Probability
1.0
0.8
0.6
0.4
0.2
0.0
126 65 6 98 51 12 70 29 18 50 24 9 30 19 36 14 4 42 2 48 7 54 5 1 60
No.at risk
P+G G
Median PFS, months (95%CI)
16.2 months (12.6, 18.7)
11.1 months (9.7, 13.8)
Pemetrexed + gefitinib
Gefitinib
Adjusted HR 0.67 (95%CI 0.5, 0.9)
1-sided p=0.009
Chih-Hsin Yang J et al. Ann Oncol 2018;29(suppl 5):abstr 1381PD

53. 1382PD: Phase III study of gefitinib (G) versus gefitinib+carboplatin+pemetrexed (GCP) as 1st-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009) – Seike M, et al
Study objective
To investigate the efficacy and safety of gefitinib + carboplatin + pemetrexed vs. gefitinib in patients with non-squamous NSCLC
Induction phase
Maintenance phase
Gefitinib 250 mg/day + carboplatin AUC6 + pemetrexed 500 mg/m2
Gefitinib + pemetrexed q3w
Key patient inclusion criteria
Treatment naïve patients with non-squamous IIIB/IV NSCLC
EGFR+
PS 0–1
(n=345)
Stratification
Sex
EGFR mutation
Smoking history R
1:1
Gefitinib 250 mg/day
Platinum-based regimen
Primary endpoints
PFS, PFS2, OS
Secondary endpoints
ORR, safety, QoL
Seike M, et al. Ann Oncol 2018;29(suppl 5):Abstr 1382PD

54. Progression-free survival, %
1382PD: Phase III study of gefitinib (G) versus gefitinib+carboplatin+pemetrexed (GCP) as 1st-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009) – Seike M, et al
Results
Conclusions
PFS and OS were significantly improved in patients treated with combination therapy of gefitinib + carboplatin + pemetrexed
There was no difference in PFS2
PFS
Updated OS
Overall survival, %
Time, months
100 80 60 40 20
172
170 12
153
162 24
115
131 36 86
106 48 62 77 26 29
No. at risk
Gefitinib
Gef + carb + pem
Progression-free survival, %
Time, months
100 80 60 40 20
172
169 12 78
123 24 29 68 36 11 37 48 2 10
No. at risk
Gefitinib
Gef + carb + pem
Gefitinib
Gefitinib + carb + pem
Median PFS, months (95%CI)
11.2 (9.0, 13.4)
20.9 (18.0, 24.0)
HR (95%CI); p-value
0.490 (0.388, 0.620); <0.001
Gefitinib
Gefitinib + carb + pem
mOS, months (95% CI)
38.8 (31.1, 47.3)
50.9 (41.8, 62.5)
HR (95%CI); p-value
0.72 (0.58, 0.95); 0.02
Seike M, et al. Ann Oncol 2018;29(suppl 5):Abstr 1382PD

55. 1385PD: A randomised phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC – the ETOP and EORTC SPLENDOUR trial – Peters S, et al
Study objective
To investigate the efficacy of denosumab as an add-on to standard 1L doublet chemotherapy + BSC in patients with NSCLC in the SPLENDOUR study
Denosumab 120 mg every 3–4 weeks + chemotherapy (4–6 cycles)
(n=255)
Key patient inclusion criteria
Stage IV NSCLC
(n=514)
Stratification
Bone metastases PS
Histology
Region R
1:1
Chemotherapy (4–6 cycles) + BSC*
(n=259)
Primary endpoint OS
Secondary endpoints
PFS, OS by bone metastases, safety
*Zoledronic acid in case of skeletal involvement
Peters S, et al. Ann Oncol 2018;29(suppl 5):Abstr 1385PD

56. 1385PD: A randomised phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC – the ETOP and EORTC SPLENDOUR trial – Peters S, et al
Key results OS
PFS
OS, %
100 80 60 40 20 2 3 4 1 29 23 83 82
259
255
Years
PFS, %
100 80 60 40 20 28 36 12 6 5 4 2 29 19
259
254
Months 24 32 16 1 13 10
140
138 8 55 50
Denosumab
BSC
Denosumab
BSC
No. at risk
Denosumab
BSC
No. at risk
Denosumab
BSC
Non-parametric
Cox model
Treatment
Events/ patients
Median, years (95%CI)
1 year, % (95%CI) HR
(95%CI)
p-value (Score test)
Denosumab
177/258
0.68 (0.62, 0.87)
40.2 (33.8, 46.5)
0.96 (0.78, 1.18)
BSC
178/255
0.73 (0.63, 0.92)
1.00
0.689
Non-parametric
Cox model
Treatment
Events/ patient
Median, years (95%CI)
1 year, % (95%CI)
HR (95%CI)
p-value (Score test)
Denosumab
228/259
0.39 (0.35, 0.44)
13.1 (9.1, 17.9)
0.97 (0.81, 1.17)
BSC
227/254
0.39 (0.34, 0.44)
9.3 (6.0, 13.6)
1.00
0.777
Peters S, et al. Ann Oncol 2018;29(suppl 5):Abstr 1385PD

57. Denosumab added to 1L platinum-based chemotherapy did not improve OS
1385PD: A randomised phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC – the ETOP and EORTC SPLENDOUR trial – Peters S, et al
Key results (cont.)
Conclusions
Denosumab added to 1L platinum-based chemotherapy did not improve OS
There were no safety concerns with denosumab
OS Bone metastases
OS No bone metastases
OS, %
100 80 60 40 20 28 12 15 14 7 36 41 N
138
137
Months 4 24 32 16 17 13 5 3 27 25 87 95 8 50 53 2
OS, %
100 80 60 40 20 28 36 12 19 14 7 6 47 41 N
121
118
Months 4 24 32 16 10 2 35 95 87 8 65 66
Denosumab
BSC
Denosumab
BSC
No. at risk
Denosumab
BSC
No. at risk
Denosumab
BSC
Non-parametric
Cox model
Treatment
Events/ patients
Median, years (95%CI)
1 year, % (95%CI)
HR (95%CI)
p value (Score test)
Denosumab
98/138
0.62 (0.46, 0.73)
34.4 (26.1, 43.0)
1.03 (0.78, 1.37)
BSC
98/137
0.61 (0.51, 0.82)
35.8 (27.5, 44.2)
1.00
0.816
Non-parametric
Cox model
Treatment
Events/ patients
Median (years) (95%CI)
1 year, % (95%CI)
Hazard Ratio (95%CI)
P-Value (Score test)
Denosumab
79/121
0.89 (0.67, 1.35)
46.9 (37.2, 55.9)
0.89 (0.65, 1.22)
BSC
80/118
0.92 (0.71, 1.05)
45.4 (35.7, 54.6)
1.00
0.483
Peters S, et al. Ann Oncol 2018;29(suppl 5):Abstr 1385PD

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

59. LBA63: Long-term survival in patients (pts) with advanced NSCLC in the KEYNOTE-010 study overall and in pts who completed 2 years of pembrolizumab (pembro) – Herbst RS, et al
Study objective
Long-term follow-up of KEYNOTE-010 investigating pembrolizumab vs. docetaxel in patients with advanced NSCLC and PD-L1 TPS ≥1% who had progressed after platinum-containing chemotherapy
Pembrolizumab 2 mg/kg q3w for 24 months
Key patient inclusion criteria
Advanced NSCLC
PD-L1 TPS ≥1%
Progression after ≥1 line of chemotherapy
No active brain metastases
Pembrolizumab 10 mg/kg q3w for 24 months R
1:1:1
Docetaxel 75 mg/m2 q3w
Stratification
ECOG PS (0 vs. 1)
Region (East Asia vs. non-East Asia)
PD-L1 status (TPS ≥50% vs. 1–49%)
Endpoints in TPS ≥50% and ≥1% populations
OS, PFS
ORR, DoR, safety
Herbst RS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA63

60. LBA63: Long-term survival in patients (pts) with advanced NSCLC in the KEYNOTE-010 study overall and in pts who completed 2 years of pembrolizumab (pembro) – Herbst RS, et al
Key results OS
PD-L1 TPS ≥50% population
PD-L1 TPS ≥1% population N
Events, n (%)
Median OS, mo (95%CI)
HR (95%CI); p-value
Pembrolizumab
290
199 (69)
16.9 (12.3, 21.4)
0.53 (0.42, 0.66); <
Docetaxel
152
127 (84)
8.2 (6.4, 9.8) N
Events, n (%)
Median OS, mo (95%CI)
HR (95%CI); p-value
Pembrolizumab
690
548 (79)
11.8 (10.4, 13.1)
0.69 (0.60, 0.80); <
Docetaxel
343
295 (86)
8.4 (7.6, 9.5)
Overall survival, %
100 80 60 40 20
290
152 5
229 97 10
178 58 15
149 39
131 29 25
115 23 35 94 18 50 45 26 8 1 55 30
101 21
Time, months
35%
13%
Overall survival, %
100 80 60 40 20
690
343 5
523
226 10
374
135 15
295 90
248 57 25
211 44 35
151 86 45 13 50 2 55 30
171
Time, months
23%
11%
No. at risk
Pembro
Docetaxel
No. at risk
Pembro
Docetaxel
Herbst RS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA63

61. LBA63: Long-term survival in patients (pts) with advanced NSCLC in the KEYNOTE-010 study overall and in pts who completed 2 years of pembrolizumab (pembro) – Herbst RS, et al
Key results (cont.)
Overall, median treatment duration was 3.5 months (range 0.03–31.7) in the pembrolizumab group (n=682) and 2.0 months (range 0.03–26.4) in the docetaxel group (n=309)
79 patients completed 35 cycles or 2 years of pembrolizumab with a median follow-up of 43.4 months (range 35.7–49.8)
75/79 (95%) patients had a CR or PR
48/75 (64%) patients had ongoing response, median DoR NR (range 4–46+ months)
Median OS was NR (95%CI NR, NR)
The Kaplan-Meier estimate of 36-month OS rate was 98.7% (95%CI 91.2, 99.8)
25/79 (32%) patients had PD after stopping 35 cycles or 2 years of pembrolizumab
In 14 patients who received a second course of pembrolizumab after 35 cycles or 2 years of treatment and subsequent PD, 6 (43%) had PR and 5 (36%) had SD
Conclusions
In patients with PD-L1-expressing advanced NSCLC, pembrolizumab continued to prolong OS compared with docetaxel
In patients who completed 2 years of pembrolizumab AEs were manageable and responses were durable
Herbst RS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA63

62. 1378O: ARCTIC: durvalumab + tremelimumab and durvalumab monotherapy vs SoC in ≥3L advanced NSCLC treatment – Kowalski DM, et al
Study objective
To investigate the efficacy and safety of durvalumab vs. SoC and the combination of durvalumab + tremelimumab vs. SoC in subgroups based on PD-L1 expression (≥25% or <25%) in the ARCTIC study
Durvalumab 10 mg/kg q2w for up to 12 mo
(n=62)
Study A
PD-L1 TC
≥25%
(n=126) R
1:1
Key patient inclusion criteria
Stage IIIB/IV NSCLC
≥2 prior treatments
Immunotherapy-naïve
EGFR/ALK wild-type
WHO PS 0/1
SoC*
(n=64)
Durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w for 12 weeks then durvalumab 10 mg/kg for 34 weeks (n=174)
Study B
PD-L1 TC
<25%
(n=469)
SoC*
(n=118)
Stratification
Planned SoC, histology R
3:2:2:1
Durvalumab 10 mg/kg q2w for up to 12 mo (n=117)
Tremelimumab 10 mg/kg q4w for 24 weeks then q12w for 24 weeks (n=60)
Primary endpoint
OS, PFS (investigator assessed
Secondary endpoints
1-year OS and PFS rates, ORR, safety
*Erlotinib, gemcitabine, or vinorelbine
Kowalski DM, et al. Ann Oncol 2018;29(suppl 5):Abstr 1378O

63. 1378O: ARCTIC: durvalumab + tremelimumab and durvalumab monotherapy vs SoC in ≥3L advanced NSCLC treatment – Kowalski DM, et al
Key results
Study A
Probability of OS
Time from randomisation, months
1.0
0.8
0.6
0.4
0.2
0.0 62 64 3 53 45 6 35 9 37 27
No. at risk
Durvalumab
SoC 12 30 19 15 25 18 21 10 24 16 8 4 33
OS (PD-L1 TC ≥25%)
31.3%
49.3%
Durvalumab(n=62)
SoC (n=64)
Events, n (%)
48 (77.4)
55 (85.9)
Median OS, months (95%CI)
11.7
(8.2, 17.4)
6.8
(4.9, 10.2)
HR (95%CI)
0.63 (0.42, 0.93)
Durvalumab(n=62)
SoC (n=64)
Events, n (%)
58 (93.5)
58 (90.6)
Median PFS, months (95%CI)
3.8 (1.9, 5.6)
2.2 (1.9, 3.7)
HR (95%CI)
0.71 (0.49, 1.04)
Probability of PFS
Time from randomisation, months
1.0
0.8
0.6
0.4
0.2
0.0 62 64 3 34 25 6 22 14 9 18 10
No. at risk
Durvalumab
SoC 12 5 15 2 7 21 24 1 27 30 33
PFS (PD-L1 TC ≥25%)
9.9%
19.4%
Kowalski DM, et al. Ann Oncol 2018;29(suppl 5):Abstr 1378O

64. 1378O: ARCTIC: durvalumab + tremelimumab and durvalumab monotherapy vs SoC in ≥3L advanced NSCLC treatment – Kowalski DM, et al
Key results (cont.)
Conclusions
Clinically meaningful improvement in OS was seen with durvalumab vs. SoC in the PD-L1 TC ≥25% subgroup
Combination therapy led to non-significant improvement in OS vs. SoC in PD-L1 TC <25% subgroup
Study B
Probability of OS
Time from randomisation, months
1.0
0.8
0.6
0.4
0.2
0.0
174
118 3
137 97 6
111 70 9 93 55
No. at risk
D + T
SoC
Durvalumab + tremelimumab 12 82 44 15 67 35 18 56 27 21 33 14 24 7 1 30
OS (PD-L1 TC <25%)
38.8%
49.5%
PFS (PD-L1 TC <25%)
Probability of OS
Time from randomisation, months
0.8
0.6
0.4
0.2
0.0
174
118 3 90 51 6 49 25 9 41 13
No. at risk
D + T
SoC 12 31 15 23 18 17 21 11 1 24 27 30
8.0%
20.6%
1.0
Durvalumab + tremelimumab
SoC
D + T (n=174)
SoC (n=118)
Events, n (%)
118 (67.8)
90 (76.3)
mOS, months (95%CI)
11.5 (8.7, 14.1)
8.7 (6.5, 11.7)
HR (95%CI)
0.80 (0.61, 1.05), p=0.109
D + T (n=174)
SoC (n=118)
Events, n (%)
146 (83.9)
92 (78.0)
mPFS, months (95%CI)
3.5 (2.3, 4.6)
3.5 (1.9, 3.9)
HR (95%CI)
0.77 (0.59, 1.01), p=0.056
Kowalski DM, et al. Ann Oncol 2018;29(suppl 5):Abstr 1378O

65. SCLC, mesothelioma and thymic epithelial tumours
Other malignancies
SCLC, mesothelioma and thymic epithelial tumours

66. 1665PD: Preliminary efficacy of durvalumab plus tremelimumab in platinum-refractory/resistant EDSCLC from arm A of the phase II BALTIC study – Bondarenko I, et al
Study objective
To determine the efficacy and safety of durvalumab + tremelimumab in patients from the BALTIC study with extensive-disease (ED) SCLC who have platinum- refractory or -resistant disease
Key patient inclusion criteria
ED-SCLC
Refractory or resistant to 1L chemotherapy
Life expectancy ≥8 weeks
No prior exposure to immunotherapy
WHO/ECOG PS 0–1
Cohort A: Durvalumab 1500 mg + tremelimumab 75 mg q4w for up to 4 months, then durvalumab 1500 mg q4w (n=10)
Interim analysis*
Primary endpoint
ORR
Secondary endpoints
DCR at 12 weeks, DoR, TTR, PFS, OS, safety
*Interim ORR analysis followed by expansion stage with n=20
Bondarenko I, et al. Ann Oncol 2018;29(suppl 5):Abstr 1665PD

67. Maximum percentage change in target lesion size
1665PD: Preliminary efficacy of durvalumab plus tremelimumab in platinum-refractory/resistant EDSCLC from arm A of the phase II BALTIC study – Bondarenko I, et al
Key results
Confirmed ORR was 9.5% (95%CI 1.2, 30.4) with PR in 2 patients
Median PFS was 1.9 months (95%CI 1.8, 4.3)
Median OS was 6.0 months (95%CI 1.9, 12.0)
Conclusion
In patients with platinum-refractory ED-SCLC, durvalumab + tremelimumab showed promising activity, with a safety profile consistent with previous reports
Maximum percentage change in target lesion size
Best change from baseline in target lesion size, %
100 80 60 40 20
–20
–40
–60
–80
–100
Non-response
Response
Bondarenko I, et al. Ann Oncol 2018;29(suppl 5):Abstr 1665PD

68. NCF was tested prior to PCI and at weeks 11, 29 and 53
1667PD: Impact of early prophylactic cranial irradiation with hippocampal avoidance on neurocognitive function in patients with limited disease small-cell lung cancer. A multicenter phase II trial (SAKK 15/12) – Vees H, et al
Study objective
To investigate the neurocognitive function (NCF) in patients with limited-disease SCLC treated with prophylactic cranial irradiation (PCI) concomitant with chemotherapy and thoracic radiotherapy (tRT) in the SAKK 15/12 study
Methods
Patients received hippocampal avoidance PCI at the start of the 2nd cycle of chemotherapy (cisplatin or carboplatin and etoposide) and tRT (total of 6 cycles of chemotherapy)
NCF was tested prior to PCI and at weeks 11, 29 and 53
Memory was assessed using Hopkins Verbal Learning Test Revised (HVLT-R); language and verbal fluency was assessed using Controlled Oral Word Association Test (COWAT); visual search, scanning, speed of processing and executive function was assessed using Trail Making Tests A and B (TMT A&B)
NCF decline was defined as a decrease of 1 SE of measurement in any test
A rate of ≤30% in patients with no NCF decline was assumed unpromising and a rate of ≥50% in patients with no NCF decline was assumed promising
Vees H, et al. Ann Oncol 2018;29(suppl 5):Abstr 1667PD

69. Deterioration of NCF by cognitive test
1667PD: Impact of early prophylactic cranial irradiation with hippocampal avoidance on neurocognitive function in patients with limited disease small-cell lung cancer. A multicenter phase II trial (SAKK 15/12) – Vees H, et al
Key result
No brain metastases were observed during 6 months
OS was 87% (95%CI 72, 94)
Overall 7 patients died: 4 due to disease progression, 1 due to respiratory failure, 1 due to haemorrhage and 1 for unknown reason
The most common grade ≥3 AEs were: anaemia (21%), febrile neutropenia (19%) and fatigue (14%)
Conclusion
The proportion of patients with no decline in NCF at 6 months is similar to that in those receiving sequential PCI
Deterioration of NCF by cognitive test
Deterioration of NCF at 6 months
Deterioration of NCF
n (%)
90%CI No
13 (34.2)
21.6, 48.8
Yes
25 (65.8)
Number of patients
Vees H, et al. Ann Oncol 2018;29(suppl 5):Abstr 1667PD