Healio recently published results of the CheckMate 649 study confirming the benefits of combining nivolumab and chemotherapy in treating newly diagnosed patients with gastroesophageal junction cancer and advanced gastric and esophageal cancers.
Follow-up data for chemotherapy plus nivolumab suggests the combination will be the new first-line therapy that has been approved in a decade to improve survival for these patients. It is also the first immunotherapy to be approved for the aforementioned disorders.
About the Studies
A total of 1,581 patients were randomly assigned to treatment with either chemotherapy or nivolumab combined with chemotherapy in one of the analyses.
In a second study, a total of 813 patients were randomly assigned to chemotherapy or nivolumab combined with ipilimumab.
The investigators followed up in twenty-four months for the chemotherapy/nivolumab arm and in thirty-five months in the ipilimumab/nivolumab arm.
Results of the duration of treatment were:
- 6.8 months duration for chemotherapy/nivolumab
- 1.9 months for ipilimumab/nivolumab
- 4.9 months for chemotherapy
A greater number of patients in the ipilimumab/nivolumab arm left the study reporting adverse events as follows:
- 19% in ipilimumab/nivolumab arm
- 8% in the chemotherapy/nivolumab arm
- 6% in the chemotherapy arm
There was no new information (safety signals) about adverse events that would require further investigation.
Note that the single-agent chemotherapy consisted of FOLFOX every two weeks and XELOX administered every three weeks.
About the Third Arm of the Study
The Study’s Third Arm, nivolumab plus ipilimumab, was conducted to test the efficacy of chemotherapy-free treatment on patients who had advanced gastric cancer.
The results were not impressive. Researchers found that nivolumab (Opdivo) combined with ipilimumab (Yervoy) did not improve overall survival or the response rate when compared to chemotherapy administered as a single agent.
It should be noted that a high dose of ipilimumab was used in the Phase 3 study yet the adverse events reported were lower in the nivolumab/ipilimumab arm than in the two cohorts treated with chemotherapy.
This should be an indication that the lower benefit from the chemotherapy-free arm is not due to toxicity. Rather it indicates the advantage of chemotherapy against gastric cancer.
On the other hand, nivolumab and chemotherapy/nivolumab’s reported benefits indicate that gastric adenocarcinoma is not entirely immune sensitive and requires multiple interventions for disease control.
Dr. Afsaneh Barzi, chief of oncology service at MSK Cancer Center, recently spoke at the ESMO Congress symposium. Dr. Barzi said that platinum-based chemotherapy was considered the standard of care in treating metastatic gastric adenocarcinoma.
The Doctor said that CheckMate 649 has brought progress in the form of extending median survival to over twelve months.