The FDA approved nivolumab (Opdivo) for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy, according to Bristol Meyers Squibb – the agent’s manufacturer.
The agency based the priority review and approval on results from the multicenter, randomized, active-controlled, open-label global phase 3 ATTRACTION-3 trial – designed to evaluate nivolumab (n = 210), compared with taxane chemotherapy (docetaxel or paclitaxel; n = 209). The trial included patients regardless of tumor PD-L1 status.
Researchers randomized patients to receive either 240 mg IV nivolumab over 30 minutes every 2 weeks or investigator’s choice of taxane chemotherapy (either 75 mg/m2 IV docetaxel every 3 weeks [n = 65] or 100 mg/m2 paclitaxel once a week for 6 weeks followed by 1 week off [n = 144]). Patients were treated until disease progression or unacceptable toxicity.
Overall survival (OS) served as the primary end point. Secondary end points included investigator-assessed overall response rate (ORR) and progression-free survival (PFS), and duration of response (DOR).
In the trial, patients treated with Opdivo demonstrated superior median OS, compared with chemotherapy (10.9 months versus 8.4 months).
Researchers found no statistically significant difference in ORR (19.3% [95% CI, 13.7-26.0] vs 21.5% [95% CI, 15.4-28.8]; P
= .6323) between the 2 arms. Among patients treated with nivolumab, 0.6% experienced a complete response and 18.7% with a partial response, compared with those treated with chemotherapy (1.3% and 20.3%, respectively).
Median PFD was 1.7 months (95% CI, 1.5-2.7) in the Opdivo arm, compared with 3.4 months (95% CI. 3.0-4.2) in the investigator’s choice chemotherapy arm (HR, 1.1; 95% CI, 0.9-1.3).
Safety was evaluated in 209 patients. Serious adverse events (AEs) occurred in 38% of patients given nivolumab, including pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. Fatal AEs consisted of interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).
Treatment was discontinued in 3% of patients and was delayed in 27% of patients due to AEs.
The most common AEs, occurring in 20% or more of patients treated with nivolumab, included rash (22%) and decreased appetite (21%).
“Many cases of esophageal cancer are diagnosed at the advanced stage, when the disease could have a significant impact on a patient’s health. Treatment options can be limited once patients with advanced esophageal squamous cell carcinoma progress,” Adam Lenkowsky, general manager and head of US oncology, immunology and cardiovascular at Bristol Myers Squibb, said in a press release.
“The approval of Opdivo as a new treatment option for previously treated patients with advanced esophageal squamous cell carcinoma, regardless of PD-L1 expression, highlights our commitment to providing new options to address the unmet needs of patients and brings us another step closer to understanding the full potential of immunotherapy for gastrointestinal cancers,” he added.
Bristol Meyers Squibb. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) for the Treatment of Patients with Advanced Esophageal Squamous Cell Carcinoma (ESCC) After Prior Fluoropyrimidine- and Platinum-based Chemotherapy. Published June 10, 2020. https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-opdivo-nivolumab-trea
. Accessed June 10, 2020.