Opdivo Combined with Yervoy or Chemo Improves Survival in Unresectable and Advanced Esophageal Cancer

Updated findings from a clinical trial demonstrated that combining Opdivo (nivolumab) with either chemotherapy or Yervoy (ipilimumab) induced an improved survival in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, compared with chemotherapy alone.

“Advanced esophageal squamous cell carcinoma carries a poor prognosis, with a median survival of around 10 months,” said Dr. Ian Chau, a consultant medical oncologist at the Royal Mardsen Hospital in the United Kingdom, during a press briefing of the data prior to the 2021 American Society of Clinical Oncology Annual Meeting.

The phase 3 CheckMate-648 evaluated the efficacy of the following treatment regimens in adult patients with histologically confirmed squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus that is deemed inoperable and cannot be treated with chemoradiation with curative intent:

• Opdivo plus fluorouracil and cisplatin (321 patients).
• Opdivo plus Yervoy (325 patients).
• Cisplatin and fluorouracil (324 patients).

Measuring overall survival and progression-free survival among patients whose tumors had PD-L1 expression 1% or more served as the main goals of the study. Other goals included assessing overall survival and progression-free survival (time during and after treatment when the patient lives without disease progression) among all patients, as well as objective response rate (the percentage of patients with partial and complete responses to the treatment) among both patient groups.

At a minimum follow-up of 12.9 months, median overall survival in patients with PD-L1 of 1% or more in the Opdivo plus chemotherapy group (158 patients) was 15.4 months and 13.7 months in the Opdivo plus Yervoy group (158 patients). In the PD-L1-positive patients in the chemotherapy alone group (157 patients), median overall survival was 9.1 months.

“This translates into over six months (of) improvement in median overall survival (when comparing Opdivo plus chemotherapy to chemotherapy alone),” Chau said. “But importantly, if you look at the latter parts of overall survival … they’re widely separated in favor of (Opdivo) plus chemo, meaning that there were more patients with prolonged overall survival.”

In the overall study population — regardless of PD-L1 expression — the median overall survival in the Opdivo plus chemotherapy group was 13.2 months; 12.8 months in the Opdivo plus Yervoy group; and 10.7 months in the chemotherapy alone group.

The objective response rate in patients with PD-L1-positive tumors administered Opdivo plus Yervoy was 35%. In the chemotherapy group it was 20%. In all patients, the objective response rate was 28% and 27% in the Opdivo plus Yervoy and Yervoy plus chemotherapy groups, respectively.

In terms of safety, the most common (occurring in 10% or more) treatment-related side effects for the chemotherapy-containing treatment groups were nausea, decreased appetite, and stomatitis (swelling and sores found inside the mouth). For the Opdivo/Yervoy group, common treatment-related side effects included rash, itch, and hypothyroidism.

Ultimately, treatment regimens that contain Opdivo have the potential to drastically improve outcomes in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma — a group that tends to have poor prognoses.

“(Opdivo) plus chemotherapy (and Opdivo plus Yervoy) each represents a new potential first-line standard of care for patients with advanced esophageal squamous cell carcinoma, based on the results of CheckMate-648, the largest randomized control trial conducted in this setting to date,” Chau concluded.

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