Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial

Narikazu Boku; Takeshi Omori; Kohei Shitara; Shinichi Sakuramoto; Kensei Yamaguchi; Ken Kato; Shigenori Kadowaki; Kunihiro Tsuji; Min-Hee Ryu; Do-Youn Oh; Sang Cheul Oh; Sun Young Rha; Keun-Wook Lee; Ik-Joo Chung; Sun Jin Sym; Li-Tzong Chen; Jen-Shi Chen; Li-Yuan Bai; Takashi Nakada; Shunsuke Hagihara; Reina Makino; Eiji Nishiyama; Yoon-Koo Kang

doi:10.1007/s10120-024-01535-0

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Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial

Authors: Narikazu Boku ; Takeshi Omori ; Kohei Shitara ; Shinichi Sakuramoto ; Kensei Yamaguchi ; Ken Kato ; Shigenori Kadowaki ; Kunihiro Tsuji ; Min-Hee Ryu ; Do-Youn Oh ; Sang Cheul Oh ; Sun Young Rha ; Keun-Wook Lee ; Ik-Joo Chung ; Sun Jin Sym ; Li-Tzong Chen ; Jen-Shi Chen ; Li-Yuan Bai ; Takashi Nakada ; Shunsuke Hagihara ; Reina Makino ; Eiji Nishiyama ; Yoon-Koo Kang

Citation: GASTRIC CANCER, Vol.27(6) : 1287-1301, 2024-11

Journal Title: GASTRIC CANCER

ISSN: 1436-3291

Issue Date: 2024-11

MeSH: Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols* / therapeutic use ; Capecitabine / administration & dosage ; Double-Blind Method ; Drug Combinations ; Esophageal Neoplasms / drug therapy ; Esophageal Neoplasms / mortality ; Esophageal Neoplasms / pathology ; Esophagogastric Junction* / pathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local* / drug therapy ; Nivolumab* / administration & dosage ; Nivolumab* / therapeutic use ; Oxaliplatin / administration & dosage ; Oxaliplatin / therapeutic use ; Oxonic Acid / administration & dosage ; Oxonic Acid / therapeutic use ; Receptor, ErbB-2* / metabolism ; Stomach Neoplasms* / drug therapy ; Stomach Neoplasms* / mortality ; Stomach Neoplasms* / pathology ; Survival Rate ; Tegafur / administration & dosage ; Tegafur / therapeutic use

Keywords: Chemotherapy ; Gastric cancer ; Nivolumab ; Oxaliplatin ; Randomized controlled trial

Abstract: Background: Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited.

Methods: ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur-gimeracil-oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints-centrally assessed progression-free survival (PFS) and overall survival (OS)-and landmark analyses of OS among patients alive using 3-year follow-up data.

Results: At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55-0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75-1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy.

Conclusion: This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer.

Trial registration: NCT02746796.