Nivolumab plus chemotherapy prolongs PFS in gastric, gastroesophageal junction cancer
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The addition of nivolumab to first-line chemotherapy significantly improved PFS, but not OS, for patients with advanced or recurrent HER2-negative gastric and gastroesophageal junction cancer, according to phase 3 study findings.
Results of the double-blind, randomized ATTRACTION-4 trial, presented at ESMO Virtual Congress 2020, also showed a higher objective response rate and more durable responses with the combination than with chemotherapy alone, researchers noted.
“Nivolumab [Opdivo, Bristol Myers Squibb] has shown significant survival benefit for heavily pretreated patients with advanced or recurrent gastric and gastroesophageal junction cancer,” Narikazu Boku, MD, PhD, deputy director of the National Cancer Center Hospital in Tokyo, said during a presentation.
“ATTRACTION-4 is a randomized, multicenter, phase 2/phase 3 study of nivolumab plus chemotherapy as first-line treatment in patients with HER2-negative, advanced gastric and gastroesophageal junction cancer," he added. The phase 2 part of ATTRACTION-4 showed promising results for nivolumab plus chemotherapy.”
The phase 3 portion of the trial included 724 Asian patients across 130 centers in Japan, Korea and Taiwan with previously untreated advanced or recurrent gastric and gastroesophageal junction cancer. Researchers randomly assigned the patients to either 360 mg IV nivolumab once every 3 weeks plus chemotherapy (n = 362) or placebo plus chemotherapy (n = 362) until disease progression or unacceptable toxicity.
The investigators performed tumor assessments every 6 weeks through week 54, followed by every 12 weeks. Centrally assessed PFS and OS served as co-primary endpoints. For the purpose of the study, researchers deemed the primary objective to be achieved if at least one of the null hypotheses of the primary endpoint was rejected.
Median follow-up for the interim analysis (primary for PFS) was 11.6 months.
Results showed median PFS of 10.45 months in the nivolumab group vs. 8.34 months in the placebo group (HR = 0.68; 98.51% CI, 0.51-0.9).
Median follow-up for the final analysis (primary for OS) was 26.6 months.
Researchers observed no significant difference in OS between the combination and chemotherapy-only groups (median, 17.45 months vs. 17.15 months; HR = 0.9; 95% CI, 0.75-1.08).
The combination group had a higher ORR (57.5% vs. 47.8%; P = .0088) and longer duration of response (12.91 months vs. 8.67 months).
Nivolumab plus chemotherapy demonstrated a manageable safety profile. However, grade 3 to grade 5 treatment-related adverse events were higher in the nivolumab group (57.9% vs. 49.2%).
“Nivolumab plus chemotherapy could be considered a new first-line treatment option in unresectable advanced or recurrent gastric and gastroesophageal junction cancer,” Boku said.
Perspective
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Elizabeth Smyth, MD
Although the incidence of gastric cancer is declining, it is still the third most common cause of cancer-associated death globally. Outside of Asia, most patients — even those fit for clinical trials — have median OS of less than 1 year.
Recent welcomed advancements in the second- and third-line settings unfortunately do not benefit most patients with gastric cancer.
For Asian patients, post-trial treatments are probably enough to explain the lack of an OS benefit, but it would be helpful to see a formal analysis to confirm this hypothesis. What is missing here is quality of life data, which I have been told is not yet ready for presentation. We need to see this before we can make a final assessment of the value of the treatment.
The results of ATTRACTION-4 represent a paradigm shift in the treatment of advanced gastric cancer. However, we need to see some refinement in the analysis of biomarker-selected subgroups to understand the value of nivolumab among all patients.
NHS Foundation Trust, U.K.
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Boku N, et al. Abstract LBA7_PR. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.
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