Study Data Shows Nivolumab Improves Overall Survival in Unresectable Advanced, Metastatic Esophageal Squamous Cell Carcinoma
Nivolumab and ipilimumab is the first dual immunotherapy combination to demonstrate a superior survival benefit compared to chemotherapy in this setting.
New data from the CheckMate-648 trial demonstrates that the use of both nivolumab (Opdivo) in combination with chemotherapy and nivolumab in combination with ipilimumab (Yervoy) significantly improved overall survival (OS) in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
This marks the third global trial in which nivolumab has shown a significant benefit for patients with upper gastrointestinal cancers, according to a press release from Bristol Myers Squibb. Furthermore, nivolumab and ipilimumab is the first dual immunotherapy combination to demonstrate a superior survival benefit compared to chemotherapy in this setting. The data were featured at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
“Patients with advanced esophageal squamous cell carcinoma face a median survival face a median survival of around 10 months when treated with chemotherapy alone and there is a clear need for treatment options beyond this current standard of care,” said Ian Chau, MD, consultant medical oncologist at the Royal Marsden NHS Foundation Trust, in a press release. “The data being presented at ASCO show that both of these nivolumab-based treatment options resulted in significant improvements in survival over chemotherapy and could offer potential new treatment options.”
Both combinations demonstrated a statistically significant and clinically meaningful OS benefit compared to chemotherapy alone at the pre-specified interim analysis in patients with unresectable advanced or metastatic ESCC with tumor cell programmed death-ligand 1 (PD-L1) expression of 1% or greater, as well as in the all-randomized population.
For the combination of nivolumab with chemotherapy, the median OS was 15.4 months compared to 9.1 months for chemotherapy alone among patients whose tumors express PD-L1. In the all-randomized patient population, the median OS was 13.2 months in the nivolumab group and 10.7 months in the all-randomized patient population. Investigators also observed a statistically significant progression-free survival (PFS) benefit in patients whose tumors express PD-L1, with a median of 6.9 months compared to 4.4 months with chemotherapy alone.
Similar results were found in patients receiving the combination nivolumab and ipilimumab, with a median OS of 13.7 months versus 9.1 months for chemotherapy alone. In the all-randomized patient population, researchers observed a median OS of 12.8 months and 10.7 months, respectively. The combination did not meet its other primary endpoint of PFS in patients whose tumors express PD-L1.
The safety profiles of both combinations were consistent with those previously reported for other tumor types. Grade 3 or 4 drug-related adverse events were observed in 47% of the nivolumab plus chemotherapy arm, in 32% of the nivolumab plus ipilimumab arm, and in 36% of the chemotherapy alone arm. The safety profile in patients with PD-L1 expression of 1% or greater was consistent with the all-randomized data, according to the press release.
“These data add to our growing body of evidence supporting the clinical benefit of Opdivo in upper GI cancers, from the late-line metastatic setting to earlier stages of disease,” said Ian Waxman, MD, development lead of gastrointestinal cancers at Bristol Myers Squibb, in the press release. “Opdivo has now demonstrated superior first-line efficacy in multiple upper GI cancers across histologies and tumor locations.”
Bristol Myers Squibb Presents Data from CheckMate-648 Showing Opdivo Plus Chemotherapy and Opdivo Plus Yervoy Significantly Improved Overall Survival Compared to Chemotherapy in Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma. News release. Bristol Myers Squibb. Released June 3, 2021. Accessed June 7, 2021. https://news.bms.com/news/details/2021/Bristol-Myers-Squibb-Presents-Data-from-CheckMate--648-Showing-Opdivo-plus-Chemotherapy-and-Opdivo-plus-Yervoy-Significantly-Improved-Overall-Survival-Compared-to-Chemotherapy-in-Unresectable-Advanced-or-Metastatic-Esophageal-Squamous-Cell-Carcinoma/default.aspx