ARCHER 1050: First-line Dacomitinib vs Gefitinib in EGFR-Mutant Advanced NSCLC CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals NSCLC, non-small-cell lung cancer. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

First-line Dacomitinib vs Gefitinib in EGFR-Mutant Advanced NSCLC: Background Dacomitinib: second-generation ErbB family TKI[1] Irreversible inhibitor of EGFR/HER1, HER2, HER4 ARCHER 1017: previous single-arm phase II examination of first- line dacomitinib in pts with EGFR-mutant NSCLC[2] ORR: 75.6%, median PFS: 18.2 mos ARCHER 1050: current phase III analysis evaluating safety, efficacy of first-line dacomitinib vs gefitinib for pts with advanced NSCLC and an EGFR-activating mutation[3] NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor. 1. Engelman JA, et al. Cancer Res. 2007;67:11924-11932. 2. Jänne PA, et al. Lancet Oncol. 2014;15:1433-1441. 3. Mok T, et al. ASCO 2017. Abstract LBA9007. Slide credit: clinicaloptions.com

ARCHER 1050: Study Design Multicenter, randomized, open-label phase III study Primary endpoint: PFS by blinded independent review Secondary endpoints: PFS by investigator assessment, ORR, DoR, TTF, OS, safety, pt-reported outcomes Stratified by race (Asian vs non-Asian), EGFR mutation (exon 19 vs 21) Dacomitinib 45 mg PO QD (n = 227) Treatment-naive pts with advanced NSCLC, EGFR-activating mutation(s), and ECOG PS 0/1; no CNS metastases or prior TKIs (N = 452) Gefitinib 250 mg PO QD (n = 225) CNS, central nervous system; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer; PS, performance status; TKI, tyrosine kinase inhibitor; TTF, time to treatment failure. Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

ARCHER 1050: Baseline Characteristics Dacomitinib (n = 227) Gefitinib (n = 225) Median age, yrs (range) < 65 yrs, n (%) 62 (28-87) 133 (58.6) 61 (33-86) 140 (62.2) Female, n (%) 146 (64.3) 125 (55.6) Race, n (%) Asian White Black 170 (74.9) 56 (24.7) 1 (0.4) 176 (78.2) 49 (21.8) ECOG PS, n (%) 1 75 (33.0) 152 (67.0) 62 (27.6) 163 (72.4) Characteristic, n (%) Dacomitinib (n = 227) Gefitinib (n = 225) Smoking status Never Former Current 147 (64.8) 65 (28.6) 15 (6.6) 144 (64.0) 62 (27.6) 19 (8.4) EGFR mutation status Exon 19 del L858R 134 (59.0) 93 (41.0) 133 (59.1) 92 (40.9) ECOG, Eastern Cooperative Oncology Group; PS, performance status. Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

ARCHER 1050: PFS by Independent Review Outcome Dacomitinib (n = 227) Gefitinib (n = 225) Median PFS, mos (95% CI)* 14.7 (11.1-16.6) 9.2 (9.1-11.0) 24-mo PFS, % 30.6 9.6 PFS Analysis by Subgroup n HR (95% CI)† All pts 452 0.58 (0.46-0.73) < 65 yrs of age ≥ 65 yrs of age 273 179 0.51 (0.39-0.69) 0.69 (0.48-0.99) Male Female 181 271 0.72 (0.51-1.02) 0.50 (0.37-0.67) ECOG PS 0 ECOG PS 1 137 315 0.65 (0.43-1.00) 0.56 (0.43-0.73) Asian Non-Asian 346 106 0.51 (0.39-0.66) 0.89 (0.57-1.39) Never smoker Former/current smoker 291 161 0.51 (0.39-0.68) 0.72 (0.49-1.05) Exon 19 del in EGFR L858R in EGFR 267 185 0.55 (0.41-0.75) 0.63 (0.44-0.88) *HR: 0.59 (95% CI: 0.47-0.74; P < .0001) Median follow-up for PFS: 22.1 mos ECOG, Eastern Cooperative Oncology Group; PS, performance status. †HR < 1 favors dacomitinib Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

ARCHER 1050: Secondary Endpoints Outcome Dacomitinib (n = 227) Gefitinib (n = 225) HR (95% CI) P Value Median PFS by investigator assessment, mos (95% CI) 16.6 (12.9-18.4) 11.0 (9.4-12.1) 0.62 (0.50-0.78) < .0001 ORR, % (95% CI) 74.9 (68.7-80.4) 71.6 (65.2-77.4) -- .3883 Median DoR, mos (95% CI) 14.8 (12.0-17.4) 8.3 (7.4-9.2) Median TTF, mos (95% CI) 11.1 (9.2-14.6) 9.2 (7.6-9.4) 0.67 (0.54-0.83) < .001 OS data not yet mature (36.9% of events at data cutoff) Pt-reported symptomatic outcomes similar between arms with following statistically significant differences: Dacomitinib: greater reduction in chest pain, increased diarrhea and sore mouth Gefitinib: greater improvement in global QoL DoR, duration of response; QoL, quality of life; TTF, time to treatment failure. Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

ARCHER 1050: Adverse Events AE Occurring in ≥ 15% in Either Arm, % Dacomitinib (n = 227) Gefitinib (n = 224) Any Gr 1 Gr 2 Gr 3 Diarrhea* 87.2 49.8 28.6 8.4 55.8 46.0 8.9 0.9 Paronychia 61.7 20.3 33.9 7.5 20.1 13.4 5.4 1.3 Dermatitis acneiform 48.9 16.3 18.9 13.7 19.2 9.4 Stomatitis 43.6 22.5 17.6 3.5 17.9 14.7 2.7 0.4 Decreased appetite 30.8 10.1 3.1 24.6 21.4 Dry skin 27.8 18.5 7.9 17.0 15.6 Weight decrease 25.6 9.7 2.2 16.5 9.8 6.3 Alopecia 23.3 18.1 4.8 12.5 11.6 Cough 21.1 17.2 4.0 18.8 16.1 Pruritis 19.8 11.9 13.8 10.7 1.8 ALT increase 19.4 39.3 8.5 AE, adverse event; ALT, alanine aminotransferase; Gr, grade. *Gr 5 diarrhea, n = 1. Otherwise, no listed AE with severity above grade 3 in either arm. Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

ARCHER 1050: Serious AE and Dose Modification Outcome Dacomitinib (n = 227) Gefitinib (n = 224) Serious AE, n (%) Any Treatment related Causing discontinuation Causing death 62 (27.3) 21 (9.3) 22 (9.7) 2 (0.9)* 50 (22.3) 10 (4.5) 15 (6.7) 1 (0.4)† Median time to dose reduction, mos (range) 2.8 (0.3-20.3) 3.3 (1.2-25.7) Median duration of dose reduction, mos (range) 11.3 (0.1-33.6) 5.2 (0.3-17.8) Reduced dose given, n (%) 30 mg/day 15 mg/day 87 (38.3) 63 (27.8) NA Pts requiring dose reduction, n (%) 150 (66.1) 18 (8.0) AE, adverse event; NA, not applicable. *Untreated diarrhea, untreated cholelithases/liver disease, n =1 each. †Sigmoid colon diverticulitis/rupture complicated by pneumonia. Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

ARCHER 1050: Conclusions In pts with advanced EGFR-mutant NSCLC, first-line dacomitinib significantly extended median PFS (either by independent review or investigator assessment), DoR, and TTF vs gefitinib Similar ORR between arms, OS data immature Dacomitinib toxicity profile consistent with previous reports Dose modifications more common than with gefitinib Higher incidence of diarrhea, skin rash, and mucositis than gefitinib Study investigators conclude that dacomitinib represents new option for treatment-naive pts with advanced EGFR-mutant NSCLC DoR, duration of response; NSCLC, non-small-cell lung cancer; TTF, time to treatment failure. Slide credit: clinicaloptions.com Mok T, et al. ASCO 2017. Abstract LBA9007.

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