Addition of Nivolumab Improves OS in Patients with Unresectable, Advanced ESCC

The addition of nivolumab (Opdivo) to either chemotherapy or ipilimumab (Yervoy) demonstrated a significant overall survival (OS) benefit among patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC), according to positive topline results from the phase 3 CheckMate-648 trial.

These data show that nivolumab is the first and only PD-1/L1 inhibitor to demonstrate superior first-line efficacy in upper gastrointestinal cancers across histologies and tumor locations.

“The results for these Opdivo-based combinations represent a significant advancement for patients with esophageal cancer who are often diagnosed after their disease has spread and would benefit from new therapeutic options,” Ian M. Waxman, MD, development lead, gastrointestinal cancers, Bristol Myers Squibb, said in a press release. “This study further demonstrates our commitment to pursue combination strategies that improve outcomes for patients with high unmet need, such as those with gastrointestinal cancers.”

In the randomized phase 3 CheckMate -648 trial, investigators evaluated nivolumab plus ipilimumab or nivolumab plus fluorouracil and cisplatin against fluorouracil plus cisplatin alone in patients with unresectable advanced or metastatic ESCC.

In the nivolumab plus ipilimumab arm, patients received 3 mg/kg nivolumab and 1 mg/kg ipilimumab every 6 weeks. In the nivolumab plus chemotherapy arm, patients received 240 mg nivolumab on day 1 and day 15, 800 mg/m²/day fluorouracil on day 1 through day 5, and 80 mg/m² cisplatin on day 1 of a 4-week cycle. Patients received Opdivo for up to 24 months or until disease progression or unacceptable toxicity, and chemotherapy until disease progression or unacceptable toxicity.

OS and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors express PD-L1, for both of the nivolumab-based combinations versus chemotherapy served as the primary end point. Secondary end points included OS and PFS by BICR in the all-randomized population.

The nivolumab-ipilimumab combination met its primary and secondary end points, demonstrating statistically significant and clinically meaningful improvements in OS among patients whose tumors expressed PD-L1 and in the all-randomized patient population. However, the combination did not improve PFS by BICR in patients whose tumors express PD-L1.

The safety profiles were consistent with those previously reported.

Bristol Myers Squibb noted it will complete an evaluation of the CheckMate-648 data, and share the results at an upcoming medical conference.

Reference:

Bristol Myers Squibb. Bristol Myers Squibb Announces Opdivo (nivolumab) plus Chemotherapy and Opdivo plus Yervoy (ipilimumab) Demonstrate Superior Survival Benefit Compared to Chemotherapy in Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma. Published April 8, 2021. https://news.bms.com/news/corporate-financial/2021/Bristol-Myers-Squibb-Announces-Opdivo-nivolumab-plus-Chemotherapy-and-Opdivo-plus-Yervoy-ipilimumab-Demonstrate-Superior-Survival-Benefit-Compared-to-Chemotherapy-in-Unresectable-Advanced-or-Metastatic-Esophageal-Squamous-Cell-Carcinoma/default.aspx. Accessed April 8, 2021.