First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis

Background In global phase III ASCEND-4 study (NCT01283516), ceritinib 750 mg/day (fasted), demonstrated statistically significant and clinically meaningful improvement in PFS by BIRC (median, 16.6 mos [95% CI: 12.6, 27.2] vs 8.1 mos [95% CI: 5.8, 11.1]; HR = 0.55; p Methods Pts with stage IIIB/IV, ALK + (centrally tested IHC), nonsquamous NSCLC, ≥1 measurable lesion per RECIST v1.1, and WHO PS 0–2 were eligible. Efficacy and safety were evaluated in Asian pts who had not received prior systemic anticancer therapy except neo-/adjuvant therapy. Data cutoff: June 24, 2016. Results Among 376 pts randomized (1:1) in the study, 158 pts were Asian, with 76 in ceritinib arm and 82 in chemotherapy arm. Of these, 25 pts (32.9%) in ceritinib arm and 21 (25.6%) in chemotherapy arm had brain metastases at baseline. Median duration of treatment exposure: 64.5 wks (ceritinib, N = 76) and 35.0 wks (chemotherapy, N = 75). Median duration from randomization to data cutoff: 18.3 mos. Ceritinib demonstrated superior PFS by BIRC (median, 26.3 mos; 95% CI: 8.6, NE; HR = 0.66) compared to chemotherapy (Table). Most common (≥50%; all grades; all-causality) AEs in ceritinib arm: diarrhea (85.5%), ALT increased (73.7%), vomiting (73.7%), AST increased (69.7%), and nausea (69.7%). Incidence of grade 3/4 AEs was Table . 1473P By BIRC (N * =158) Ceritinib 750mg N = 76 Chemotherapy N = 82 Overall response rate (ORR), % [95% CI] 65.8 [54.0, 76.3] 29.3 [19.7, 40.4] Best overall response, n (%) Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD) Non-CR/Non-PD Unknown 0 50 (65.8) 11 (14.5) 11 (14.5) 2 (2.6) 2 (2.6) 0 24 (29.3) 38 (46.3) 6 (7.3) 3 (3.7) 11 (13.4) Disease control rate (DCR), % [95% CI] 82.9 [72.5, 90.6] 79.3 [68.9, 87.4] M ‡ =50 M ‡ =24 Median DOR, months [95% CI] NE [24.7, NE] 16.4 [7.8, NE] n/N (%) 14/50 (28.0) 8/24 (33.3) % Event-free probability estimates [95% CI] 9 months 81.2 [67.0, 89.8] 76.1 [48.0, 90.4] 12 months 79.0 [64.5, 88.1] 50.8 [22.5, 73.5] 15 months 70.4 [54.0, 81.9] 50.8 [22.5, 73.5] Median PFS, months [95% CI] 26.3 [8.6, NE] 10.6 [6.7, 15.0] n/N (%) 32/76 (42.1) 45/82 (54.9) % Event-free probability estimates [95% CI] 9 months 61.0 [48.4, 71.5] 54.7 [41.8, 65.8] 12 months 61.0 [48.4, 71.5] 49.8 [37.1, 61.2] 15 months 55.9 [43.2, 66.9] 39.0 [26.9, 51.0] * Total number of patients included in the full analysis set. ‡ Total number of patients with confirmed complete response or partial response. n: Total number of events included in the analysis. N: Total number of patients included in the analysis. Conclusions In Asian pts with ALK+ NSCLC, ceritinib demonstrated durable and clinically meaningful efficacy and a safety profile consistent with overall ASCEND-4 study results. Clinical trial identification NCT01828099. Editorial acknowledgement Shilpa Garg, Novartis Healthcare Pvt Ltd. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure D.S. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-lily, Loxo; Research grant / Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer; Travel / Accommodation / Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda. S. Geater: Advisory / Consultancy: Boehringer Ingelheim; Honoraria (institution): AstraZeneca, Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca, Roche, Novartis, Boehringer Ingelheim; Full / Part-time employment: Prince of Songkla Univerisity. C.J. Yu: Honoraria (self): Roche, AstraZeneca, Ono pharma, Boehringer Ingelheim; Advisory / Consultancy: Roche, AstraZeneca, Ono pharma, Boehringer Ingelheim. T.C. Hsia: Advisory / Consultancy: Norvatis, Lilly, AZ, Roche local speaker. M.C. Lin: Advisory / Consultancy: AZ, Novartis, BI, Roche. V. Sriuranpong: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Novartis, Roche, Pfizer, Eisai, Boehringer, Taiho, MSD, BMS, Amgen; Research grant / Funding (institution): AstraZeneca, Novartis, Roche, Pfizer, Boehringer, Eisai, Taiho, Lilly, MSD. P. Sen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. F. Branle: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. M. Shi: Shareholder / Stockholder / Stock options: Novartis stock; Full / Part-time employment: Novartis. Y.L. Wu: Honoraria (self): AZ, Roche, Eli Lilly, Pfizer, MSD, BMS, BI; Advisory / Consultancy: AZ, Roche, BI; Research grant / Funding (institution): AZ, Roche. All other authors have declared no conflicts of interest.