FDA approves Opdivo-based combinations for esophageal squamous cell carcinoma
The FDA approved nivolumab plus fluoropyrimidine- and platinum-containing chemotherapy and nivolumab plus ipilimumab as first-line treatments for adults with unresectable advanced or metastatic esophageal squamous cell carcinoma.
The agency based the approvals of the nivolumab (Opdivo, Bristol Myers Squibb) regimens on results of the randomized phase 3 CheckMate -648 trial, which investigated the anti-PD-1 antibody in combination with fluorouracil and cisplatin chemotherapy (n = 321) and in combination with ipilimumab (Yervoy, Bristol Myers Squibb), an anti-CTLA-4 antibody (n = 325) compared with chemotherapy alone (n = 324).
OS and PFS by blinded independent central review among those with tumor cell PD-L1 expression of 1% or greater (n = 473) served as co-primary endpoints. OS and PFS among all patients served as secondary endpoints.
Results of the trial, presented at last year’s virtual ASCO Annual Meeting, showed the nivolumab-chemotherapy combination conferred longer OS vs. chemotherapy alone among all patients (median, 13.2 months vs. 10.7 months; HR = 0.74; 95% CI, 0.61-0.9) and among patients with PD-L1 expression of 1% or greater (median, 15.4 months vs. 9.1 months; HR = 0.54; 95% CI, 0.41-0.71).
The nivolumab-ipilimumab combination also significantly prolonged OS vs. chemotherapy among all patients (median, 12.8 months, HR = 0.78; 95% CI, 0.65-0.95) and among patients with PD-L1 expression of 1% or greater (median, 13.7 months; HR = 0.64; 95% CI, 0.49-0.84).
PFS met statistical significance only among patients with PD-L1 expression of 1% or greater who received nivolumab plus chemotherapy vs. chemotherapy alone (median, 6.9 months vs. 4.4 months; HR = 0.65; 95% CI, 0.49-0.86).
More than one-third of patients (39%) who received nivolumab plus chemotherapy and 23% of those who received nivolumab plus ipilimumab discontinued at least one treatment. Serious adverse reactions occurred among 62% of patients in the nivolumab-chemotherapy group and 69% of patients in the nivolumab-ipilimumab group. These included pneumonia (11% and 10%), dysphagia (7% and 3.7%) and pyrexia (2.3% vs. 4.3%). Five patients (1.6%) in each group experienced fatal adverse reactions.
“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, MD, co-first author and lead U.S. investigator of CheckMate -648, and professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said in a Bristol Myers Squibb press release. “In the CheckMate -648 trial, two nivolumab-based combinations showed a survival benefit compared [with] chemotherapy alone, offering new treatment options regardless of PD-L1 status.”
The FDA reviewed the application under its Real-Time Oncology Review pilot program.
Nivolumab-based regimens have been approved for three other indications in upper gastrointestinal cancer, including in advanced gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma.
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