FDA Approves Two Opdivo Regimens for Metastatic Esophageal Cancer

Opdivo-based treatments are now approved for five indications in upper gastroesophageal cancers.

The FDA has approved both Opdivo (nivolumab) in combination with chemotherapy and in combination with Yervoy (ipilimumab) as a first-line treatment for adult patients with advanced or metastatic esophageal squamous cell carcinoma.

Both Opdivo and Yervoy were developed by Bristol Myers Squibb. The new combinations, including Opdivo with fluoropyrimidine- and platinum-containing chemotherapy, are approved for patients regardless of PD-L1 status.

“Unresectable advanced or metastatic esophageal squamous cell carcinoma is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting,” Jaffer A. Ajani, M.D., CheckMate-648 co-first author and lead U.S. investigator, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, said in a press release.

The approvals are based on the phase 3 CheckMate-648 trial, which evaluated Opdivo in combination with chemotherapy and Opdivo plus Yervoy each compared with chemotherapy alone.

Opdivo in combination with chemotherapy demonstrated overall survival compared with chemotherapy alone, both in all randomized patients and in patients whose tumors express PD-L1. In all randomized patients the median overall survival was 13.2 months with Opdivo in combination with chemotherapy versus 10.7 months with chemotherapy alone. In patients whose tumors express PD-L1, the median overall survival was 15.4 months for Opdivo in combination with chemotherapy versus 9.1 months with chemotherapy alone.

Opdivo plus Yervoy also improved overall survival compared with chemotherapy in all-randomized patients, a secondary endpoint, and in patients whose tumors express PD-L1. The median overall survival was 12.8 months with Opdivo plus Yervoy versus 10.7 months with chemotherapy alone in all randomized patients and 13.7 months with Opdivo plus Yervoy versus 9.1 months with chemotherapy alone in patients whose tumors express PD-L1.

In the study, Opdivo and/or chemotherapy were discontinued in 39% of patients and were delayed in 71% of patients for an adverse reaction. Serious adverse reactions occurred in 62% of patients receiving Opdivo in combination with chemotherapy. The most frequent serious adverse reactions in patients receiving Opdivo/chemotherapy were pneumonia, dysphagia, esophageal stenosis, acute kidney injury, and pyrexia.

Opdivo and/or Yervoy were discontinued in 23% of patients and were delayed in 46% of patients for an adverse reaction. Serious adverse reactions occurred in 69% of patients receiving Opdivo plus Yervoy. The most frequent serious adverse reactions in patients receiving Opdivo plus Yervoy were pneumonia, pyrexia, pneumonitis, aspiration pneumonia, dysphagia, hepatic function abnormal, decreased appetite, adrenal insufficiency, and dehydration.

Opdivo is approved both as a monotherapy and in combination with chemotherapy and Yervoy for five indications in upper gastroesophageal cancers.