Chemotherapy (CT) for advanced ESCC offers poor long-term survival. We report the final analysis from the phase III ATTRACTION-3 study of the programmed death (PD)-1 inhibitor nivolumab (NIVO) versus CT in patients (pts) with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT.
Pts were enrolled regardless of PD-ligand 1 (PD-L1) expression and randomized 1:1 to either NIVO (240 mg Q2W) or investigator’s choice of paclitaxel or docetaxel. Primary endpoint was overall survival (OS).
419 pts were randomized (NIVO = 210, CT = 209). At a minimum follow-up of 17.6 months (mo; time from randomization of the last pt to data cutoff), NIVO showed a statistically significant improvement in OS vs CT (HR for death 0.77 [95% CI, 0.62–0.96; P = 0.02]; median OS, 10.9 vs 8.4 mo; Table). The proportion of pts alive at 18 mo was numerically larger with NIVO vs CT (31% vs 21%; Table). HRs for the risk of death favored NIVO over CT across tumor PD-L1 expression levels (PD-L1 ≥1%, HR 0.69 [95% CI, 0.51 to 0.94]; PD-L1 <1%, HR 0.84 [95% CI, 0.62 to 1.14]). The Table shows objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Fewer treatment-related adverse events (TRAEs) were reported with NIVO (any grade, 66%; grade 3–4, 18%) vs CT (any grade, 95%; grade 3–4, 63%; Table). NIVO showed a statistically significant overall improvement in quality of life vs CT through on-treatment week 42 in both the EQ-5D visual analog scale (least square [LS] mean, 6.9; 95% CI, 3.0–10.9; P < 0.001) and EQ-5D utility index (LS mean, 0.076; 95% CI, 0.011–0.142; P = 0.023). LBA11 Assessed in randomized pts who had target lesion measurements at baseline: NIVO, N = 171; CT, N = 158. Time from date of first response to date of first documented tumor progression or death. One grade 4 serious TRAE was not reported before the database lock and is not captured here.Efficacy (all randomized pts) NIVO N = 210 CT N = 209 Median OS, mo (95% CI) 10.9 (9.2–13.3) 8.4 (7.2–9.9) HR (95% CI; P-value) 0.77 (0.62–0.96; P = 0.02) 12-mo rate, % (95% CI) 47 (40–54) 34 (28–41) 18-mo rate, % (95% CI) 31 (24–37) 21 (15–27) ORR, n (%)a 33 (19) 34 (22) 95% CI 14–26 15–29 Median DOR,b mo (95% CI) 6.9 (5.4–11.1) 3.9 (2.8–4.2) Median PFS, mo (95% CI) 1.7 (1.5–2.7) 3.4 (3.0–4.2) HR (95% CI) 1.08 (0.87–1.34) 6-mo rate, % (95% CI) 24 (19–30) 17 (12–23) 12-mo rate, % (95% CI) 12 (8–17) 7 (4–12) Safety (all treated pts) N = 209 N = 208 Pts with TRAEs, n (%) 137 (66) 198 (95) Grade 3–4 TRAEs, n (%) 38 (18) 131 (63) Pts with serious TRAEs, n (%) 33c (16) 47 (23) Pts with TRAEs leading to discontinuation, n (%) 18 (9) 19 (9)
NIVO demonstrated superior OS and a favorable safety profile vs CT in pts with previously treated advanced ESCC, with survival benefit observed regardless of tumor PD-L1 expression. NIVO may represent a new standard second-line treatment option for pts with advanced ESCC.
NCT02569242.
Professional medical writing assistance and editorial assistance were provided by Jennifer Granit, PhD, and Christine Craig of Parexel, funded by Bristol-Myers Squibb.
Ono Pharmaceutical Co, Bristol-Myers Squibb.
Ono Pharmaceutical Co, Bristol-Myers Squibb.
B.C. Cho: Research grant / Funding (self): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD ; Licensing / Royalties: Champions Oncology; Shareholder / Stockholder / Stock options: TheraCanVac Inc; Honoraria (self): Novatis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Advisory / Consultancy: Novatis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takega, MSD; Speaker Bureau / Expert testimony: Novartis. K. Kato: Advisory / Consultancy: Ono Pharmaceutical, BeiGene, MSD, Oncolys BioPharma; Research grant / Funding (institution): Ono Pharmaceutical, Shionogi, MSD, Beigene. M. Takahashi: Research grant / Funding (self): Ono Pharmaceutical; Speaker Bureau / Expert testimony: Ono Pharmaceutical, Brystol-Myers Squibb, Daichi-Sankyo. M. Okada: Speaker Bureau / Expert testimony: Tahio Pharmaceutical, Johnson & Johnson, Coviden, Lilly, Chugai Pharma; Research grant / Funding (institution): Taiho Pharmaceutical, Nippon Kayaku, Chugai Pharma, Coviden, Johnson & Johnson, Daiichi Sanko, Yakult Honsha, Lilly Japan, Nihon Medi-Physics, Pfizer, Mochida Pharmaceuticals Co. Ltd, Shionogi. S. Kadowaki: Research grant / Funding (institution): Ono Pharmaceutical, Lilly Japan, Taiho Pharmaceutical, Boehringer Ingelheim, Bristol-Myers Squibb. Y. Doki: Speaker Bureau / Expert testimony: Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Daiichi Sankyo, Yakult Honsha, Takeda Pharmaceutical, Kaken Pharmaceutical, Abbott Japan; Research grant / Funding (self): Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Eli Lilly, MSD, Daiichi Sankyo, Yakult Honsha, Takeda Pharmaceutical, Kaken Pharmaceutical, Abbott Japan, Eisai, Shionogi . C. Yen: Honoraria (self): Lilly, Merck Sharp & Dohme, Amgen, Eisai; Advisory / Consultancy: Lilly, Merck Sharp & Dohme; Speaker Bureau / Expert testimony: Lilly, Ono Pharmaceutical, Eisai, Effective Pharmaceuticals. S. Kim: Research grant / Funding (institution): Novartis, Genzyme, Dongkook Pharma. C. Hsu: Advisory / Consultancy: Ono Pharmaceutical, Lilly, MSD, Novartis; Honoraria (self): Bristol-Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme; Research grant / Funding (institution): Ono Pharmaceutical, AstraZeneca, MSD, Genentech. I. Xynos: Shareholder / Stockholder / Stock options: Bristol-Myers Squibb. M. Kodani: Shareholder / Stockholder / Stock options: Ono Pharmaceutical Co. Ltd. Y. Kitagawa: Honoraria (self): Ethicon, Olympus, Ono Pharmaceutical, Tahi Pharmaceutical, Chugai Pharma, Nippon Kayaku, Asahi Kasei; Research grant / Funding (institution): Astellas, Otsuka, Kaken Pharmaceutical, Kyowa Hakko Kirin, Kowa, CSL Behring, Shionogi, Saiichi Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharma, Tsumura & Co., Teijin Pharma, Medtronic, Boehringer Ingelheim, Merck Serono, Novartis, Ajinomoto, Asahi Ka. All other authors have declared no conflicts of interest.