Immunotherapy in Advanced Esophagogastric Cancer
As reported in the Journal of Clinical Oncology by Janjigian et al, the phase I/II CheckMate-032 study has shown activity of nivolumab (Opdivo) and nivolumab plus ipilimumab (Yervoy) in advanced esophagogastric cancer.
In the esophagogastric cohort of the multicohort study, 160 patients (who received study treatment) with locally advanced or metastatic chemotherapy-refractory gastric, esophageal, or gastroesophageal junction cancer from 18 centers in the United States and Europe were randomized to receive nivolumab at 3 mg/kg every 2 weeks (n = 59), nivolumab at 1 mg/kg plus ipilimumab at 3mg/kg every 3 weeks for four cycles (NIV1/IPI3 group; n = 49), or nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for four cycles (NIV3/IPI1 group; n = 52). The combination regimens were followed by nivolumab at 3 mg/kg every 2 weeks.
Patients were treated until disease progression or unacceptable toxicity. Treatment beyond disease progression was permitted in patients with investigator-assessed clinical benefit. Patients in the nivolumab monotherapy group could cross over to a combination group upon disease progression. Overall, 79% of patients had received ≥ 2 prior therapies.
Treatment Responses
Median duration of follow-up was 28 months in the nivolumab group, 24 months in the NIV1/IPI3 group, and 22 months in the NIV3/IPI1 group. Investigator-assessed response was observed in 12%, 24%, and 8% of patients. Stable disease was observed in 20%, 16%, and 29% of patients.
Median durations of response were 7.1 months, 7.9 months, and not reached. Responses were observed regardless of programmed cell death ligand 1 expression status and regardless of microsatellite instability status. Progression-free survival at 12 months was 8%, 17%, and 10%. Overall survival at 12 months was 39%, 35%, and 24%.
Adverse Events
Treatment-related grade 3 or 4 adverse events occurred in 17% in the nivolumab group, 47% of the NIV1/IPI3 group, and 27% of the NIV3/IPI1 group. Treatment-related serious adverse events occurred in 10% of the nivolumab group (none with an incidence ≥ 5%), 43% (including diarrhea in 8%, adrenal insufficiency in 8%, fatigue in 6%, increased ALT in 6%, increased AST in 6%, and colitis in 6%) of the NIV1/IPI3 group, and 25% (including pneumonitis in 8%) of the NIV3/IPI1 group.
Treatment-related adverse events led to treatment discontinuation in 3%, 20%, and 13% of the groups, respectively. A death in the NIV3/IPI1 group, due to tumor-lysis syndrome, was considered treatment-related.
The investigators concluded, “Nivolumab and nivolumab plus ipilimumab demonstrated clinically meaningful antitumor activity, durable responses, encouraging long-term [overall survival], and a manageable safety profile in patients with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for esophagogastric cancers are underway.”
The study was supported by Bristol-Myers Squibb.
Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
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