Nivolumab plus oxaliplatin-based chemotherapy could be a first-line treatment option for patients with HER2-negative, advanced gastric or gastroesophageal junction (GEJ) cancer, according to researchers.
Adding nivolumab to oxaliplatin-based chemotherapy improved progression-free survival (PFS), but not overall survival (OS), in the ATTRACTION-4 trial. These results were published in The Lancet Oncology.
ATTRACTION-4 is a phase 3 trial (ClinicalTrials.gov Identifier: NCT02746796) that enrolled 724 patients with HER2-negative, unresectable, advanced, or recurrent gastric or GEJ cancer at 130 centers across Japan, South Korea, and Taiwan.
Patients were randomly assigned 1:1 to receive nivolumab plus chemotherapy or placebo plus chemotherapy. Chemotherapy consisted of intravenous oxaliplatin on day 1 plus either oral S-1 or oral capecitabine, twice daily on days 1-14 every 3 weeks. Nivolumab was given at 360 mg intravenously every 3 weeks.
At the interim analysis for PFS, the median follow-up was 11.6 months. The median PFS was 10.45 months in the nivolumab arm and 8.34 months in the placebo arm (hazard ratio [HR], 0.68; 98.51% CI, 0.51-0.90; P =.0007).
At the final OS analysis, the median follow-up was 26.6 months. The median OS was 17.45 months in the nivolumab arm and 17.15 months in the placebo arm (HR, 0.90; 95% CI, 0.75-1.08; P =.26).
The median investigator-assessed PFS at the final analysis was 8.34 months in the nivolumab arm and 6.97 months in the placebo arm (HR, 0.73; 95% CI, 0.61-0.87; P =.0003).
The objective response rate was 57% in the nivolumab arm and 48% in the placebo arm. The median duration of response was 12.91 months and 8.67 months, respectively.
Most patients in the nivolumab arm (72%) and the placebo arm (73%) received subsequent anticancer therapy.
More than 95% of patients in both study arms experienced a treatment-related adverse event (TRAE). The most common grade 3-4 TRAEs were reduced neutrophil count (20% in the nivolumab arm and 16% in the placebo arm) and reduced platelet count (9% in each arm).
Serious TRAEs of any grade occurred in 25% of patients in the nivolumab arm and 14% in the placebo arm. The most common was decreased appetite (5% and 3%, respectively).
There were 7 treatment-related deaths. Three deaths in the nivolumab arm were each due to febrile neutropenia, hepatic failure, and sudden death. Four deaths in the placebo arm were each due to sepsis, hemolytic anemia, interstitial lung disease, and respiratory failure (which occurred after the patient started subsequent anticancer therapy).
“Nivolumab combined with chemotherapy could be a new first-line treatment option to address the high unmet medical need of patients with unresectable advanced or recurrent gastric or gastroesophageal cancer,” the researchers concluded.
Disclosures: This research was supported by Ono Pharmaceutical and Bristol-Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Kang Y-K, Chen L-T, Ryu M-H, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastrooesophageal junction cancer (ATTRACTION-4): A randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. Published online January 11, 2022. doi:10.1016/S1470-2045(21)00692-6