Nivolumab plus chemotherapy shows durable efficacy in gastric, esophageal cancers
Nivolumab plus chemotherapy continued to confer clinically meaningful improvement in OS and PFS as first-line therapy for advanced gastric and esophageal cancers, according to a study presented at Gastrointestinal Cancers Symposium.
Researchers observed the sustained benefits in an expanded analysis of the randomized, global phase 3 CheckMate 649 study.
“At the primary analysis after 12 months of minimum follow-up, first-line nivolumab (Opdivo, Bristol Myers Squibb) plus chemotherapy demonstrated superior overall survival along with PFS benefit, which led to approval for [the combination] in several countries and changed the standard treatment,” Kohei Shitara, MD, chief of the department of gastrointestinal oncology at National Cancer Center Hospital East in Kashiwa, Chiba, Japan, told Healio. “At this meeting, we reported an expanded analysis after the minimum follow-up of 24 months, which was 1 year longer than that of the previous analysis.”
Background and methodology
Researchers designed CheckMate 649 to investigate chemotherapy plus nivolumab, an anti-PD-1 antibody, or nivolumab plus the CTLA-4 inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), in comparison with first-line chemotherapy alone because, although prognosis of unresectable or recurrent gastric cancer remains poor, immune checkpoint inhibition, especially PD-1 blockade, demonstrated efficacy in later lines of treatment.
The latest analyses by Shitara and colleagues included 1,581 eligible adults with previously untreated, unresectable advanced or metastatic gastric cancer, gastroesophageal cancer or esophageal adenocarcinoma, regardless of PD-L1 expression.
Within this group, researchers randomly assigned 789 patients to 360 mg nivolumab every 3 weeks or 240 mg every 2 weeks plus chemotherapy (oxaliplatin and capecitabine every 3 weeks or 5-FU and oxaliplatin every 2 weeks) and 792 patients to chemotherapy alone.
OS and PFS among patients with a PD-L1 combined positive score (CPS) of 5 or greater for nivolumab plus chemotherapy vs. chemotherapy served as dual primary endpoints. Secondary endpoints included OS with nivolumab plus chemotherapy vs. chemotherapy, first among patients with a PD-L1 CPS of 1 or greater, then among all randomly assigned patients.
Key findings
Researchers observed an OS benefit with nivolumab plus chemotherapy vs. chemotherapy across multiple subgroups.
Results showed sustained improvement in OS with the addition of nivolumab to chemotherapy among patients with PD-L1 CPS of 10 or greater (HR = 0.66; 95% CI, 0.56-0.77). Median OS among these patients also favored the nivolumab group (15 months vs. 10.9 months).
Researchers reported median PFS2 (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy or death, whichever occurred first) of 12.2 months (95% CI 11.3-13.5) in the nivolumab-chemotherapy group vs. 10.4 months (95% CI, 9.7-11.2) in the chemotherapy-alone group (HR = 0.75; 95% CI 0.67-0.84).
“Clinically meaningful improvement in OS and PFS with nivolumab plus chemotherapy was maintained with longer follow-up,” Shitara told Healio. “Also, there was an improvement in PFS2, with 25% reduction in risk of death or disease progression on subsequent therapy.
“When analyzing efficacy in various PD-L1 CPS subgroups, OS benefit with nivolumab plus chemotherapy was enriched at higher CPS cutoffs, especially with CPS 5 or higher,” Shitara added. “Meanwhile, objective responses were higher and more durable with nivolumab plus chemotherapy vs. chemotherapy, regardless of PD-L1 CPS status.”
Implications
Ongoing biomarker analyses could provide additional insight into future research, including clarifying treatment options worldwide, Shitara said. Although nivolumab plus chemotherapy is approved in the U.S. and Japan, among other countries, regardless of PD-L1 CPS status, in other countries the combination remains approved only for patients with a CPS 5 or higher.
“As shown in this presentation, some patients with a CPS of less than 5 achieve favorable outcomes since we have higher response even in this population,” Shitara said. “So, clarification of these populations by additional biomarkers might be important work.”
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Shitara K, et al. Abstract 240. Presented at: Gastrointestinal Cancers Symposium; Jan. 20-22, 2022; San Francisco.
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