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Nivolumab alone or with ipilimumab effective for heavily pretreated gastrointestinal cancers
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CHICAGO — Nivolumab alone or in combination with ipilimumab demonstrated clinical activity in Western patients with chemotherapy-refractory esophagogastric cancer regardless of PD-L1 status, according to results of the CheckMate 032 study presented at the ASCO Annual Meeting.
The regimens induced durable responses and encouraging OS, researchers wrote.
The ONO-12 study showed the anti–PD-L1 monoclonal antibody nivolumab (Opdivo, Bristol-Myers Squibb) has clinical activity among Asian patients with advanced gastric or gastroesophageal junction cancer. In that investigation, nivolumab monotherapy as third-line or later treatment extended median OS compared with placebo (5.3 months vs. 4.1 months; HR = 0.63; P < .0001).
In the multicohort phase 1/phase 2 CheckMate 032 study, Yelena Yuriy Janjigian, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues evaluated the safety and efficacy of nivolumab alone or in combination with ipilimumab (Yervoy, Bristol-Myers Squibb) — a CTLA-4 immune checkpoint inhibitor — in Western patients with advanced or metastatic chemotherapy-refractory gastric, esophageal or gastroesophageal junction cancer.
The analysis included 160 patients, all of whom had progressed on at least one prior chemotherapy regimen. Most (79%) had undergone at least two prior therapies. Nearly one-quarter (24%) had PD-L1–positive tumors (1%).
Researchers assigned patients to one of three regimens: nivolumab alone, administered in 3-mg/kg doses every 2 weeks (N3 regimen; n = 59); nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1+I3 regimen; n = 49); or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3+I1 regimen; n = 52).
Overall response rate served as the primary endpoint. Secondary endpoints included duration of response, OS, PFS and safety.
The study was not powered to compare treatment arms.
Results showed ORR of 24% among patients who received the N1+I3 regimen, 12% among those who received the N3 regimen and 8% among those who received the N3+I1 regimen.
Janjigian and colleagues reported median OS of 6.9 months in the N1+I3 group, 6.2 months among those in the N3 group and 4.8 months in the N3+I1 group. Eighteen-month OS rates were 28% among those who received N1+I3, 25% among those who received N3, and 13% among those who received N3+I1.
Among PD-L1–positive patients, researchers reported ORRs of 40% among the N1+I3 group, 19% among the N3 group and 23% among the N3+I1 group. They reported 12-month OS rates of 50% among the N1+I3 group, 34% among the N3 group and 23% among the N3+I1 group.
Among PD-L1–negative patients, results showed ORRs of 22% in the N1+I3 group, 12% in the N3 group and 0% in the N3+I1 group. Researchers reported 12-month OS rates of 32% in the N1+I3 group, 45% among the N3 group and 23% among the N3+I1 group.
Patients treated with the N1+I3 regimen experienced numerically higher rates of grade 3 or grade 4 treatment-related adverse events than those treated with the N3 or N3+I1 regimens. The most common such events were diarrhea (14% vs. 2% vs. 2%), increased alanine transaminase level (14% vs. 3% vs. 4%) and increased aspartate transaminase level (10% vs. 5% vs. 2%).
“Nivolumab alone or in combination with ipilimumab led to durable responses and encouraging OS in chemotherapy-refractory Western patients with advanced gastric, esophageal or gastroesophageal junction cancer, which is consistent with the clinical activity observed in Asian patients in the ONO-12 study,” Janjigian and colleagues wrote. “Safety was consistent with prior reports. These data support ongoing phase 3 studies investigating these regimens in patients with gastric, esophageal or gastroesophageal junction cancer.” – by Mark Leiser
Reference:
Janjigian YY, et al. Abstract 4014. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Janjigian reports research funding from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Genentech and Roche; and consultant or advisory roles with Eli Lilly and Pfizer. Other researchers report research funding and honoraria from, employment with, consultant or advisory roles with, stock ownership in and speakers bureau roles with Bristol-Myers Squibb.