Nivolumab Versus Chemotherapy in Advanced Esophageal Squamous Cell Carcinoma (ESCC): The Phase 3 ATTRACTION-3 Study

Date 30 September 2019
Event ESMO 2019 Congress
Session Presidential Symposium III
Topics Oesophageal Cancer
Gastrointestinal Cancers
Presenter Byoung Chul Cho
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors B.C. Cho1, K. Kato2, M. Takahashi3, M. Okada4, C. Lin5, K. Chin6, S. Kadowaki7, M. Ahn8, Y. Hamamoto9, Y. Doki10, C. Yen11, Y. Kubota12, S. Kim13, C. Hsu14, E. Holtved15, I. Xynos16, M. Kodani17, Y. Kitagawa18
  • 1Medical Oncology Dept, Yonsei University, 03722 - Seoul/KR
  • 2Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo/JP
  • 3Clinical Oncology, Institute of Developpment, Aging Cancer, Tohoku University, 980-8575 - Sendai/JP
  • 4Surgical Oncology, Hiroshima University, 734-8551 - Hiroshima/JP
  • 5Hematology And Oncology, China Medical University Hospital And School Of Pharmacy, China Medical University Hospital, Taichung City/TW
  • 6Medical Oncology Dept, Cancer Institute Hospital, Tokoyo/JP
  • 7Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 8Hematology-oncology, Samsung Medical Center (SMC)-Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 9Keio Cancer Center, Keio University School of Medicine, 160-8582 - Tokyo/JP
  • 10Gastroenterological Surgery, Osaka University Hospital, Osaka/JP
  • 11Medical Oncology Dept, Taipei Veterans General Hospital, 11217 - Taipei City/TW
  • 12Medical Oncology, Showa University Hospital, Tokyo/JP
  • 13Medical Oncology Dept, Asan Medical Center, University of Ulsan College of Medicine, 138-931 - Seoul/KR
  • 14Department Of Oncology, National Taiwan University Hospital, 10002 - Taipei City/TW
  • 15Clinical Oncology, Odense University Hospital, 5000 - Odense C/DK
  • 16Global Clinical Research, BMS, 08648 - Princeton/US
  • 17Department Of Oncology, ONO Pharmaceutical Co. Ltd.-Tokyo Office, 101-0041 - Tokyo/JP
  • 18Surgical Oncology, Keio University School of Medicine, 160-8582 - Tokyo/JP

Abstract

Background

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.

Methods

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).

Results

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).Table:

LBA11

Efficacy (all randomized pts)NIVO N = 210CT 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 (%)a33 (19)34 (22)
95% CI14–2615–29
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 = 209N = 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)
a

Assessed in randomized pts who had target lesion measurements at baseline: NIVO, N = 171; CT, N = 158.

b

Time from date of first response to date of first documented tumor progression or death.

c

One grade 4 serious TRAE was not reported before the database lock and is not captured here.

Conclusions

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.

Clinical trial identification

NCT02569242.

Editorial acknowledgement

Professional medical writing assistance and editorial assistance were provided by Jennifer Granit, PhD, and Christine Craig of Parexel, funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Ono Pharmaceutical Co, Bristol-Myers Squibb.

Funding

Ono Pharmaceutical Co, Bristol-Myers Squibb.

Disclosure

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.