Both the combination of nivolumab and chemotherapy and nivolumab plus ipilimumab showed a statistically significant and clinically meaningful survival benefit over chemotherapy alone in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, regardless of PD-L1 expression.
Both the combination of nivolumab (Opdivo) and chemotherapy and nivolumab plus ipilimumab (Yervoy) showed a statistically significant and clinically meaningful survival benefit over chemotherapy alone in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, regardless of PD-L1 expression, according to a press release issued by Bristol Myers Squibb.1
Full results from the study will be presented at an upcoming medical conference and with health authorities.1
The phase 3 CheckMate-648 study (NCT03143153) determine if the combination of nivolumab plus chemotherapy or nivolumab plus ipilimumab is more effective in treating esophageal cancer..1 The study had an estimated enrollment of 939 participants with an estimated completion date of August 2024. The study was spilt into 3 arms. In the first experimental arm, patients received a combination of nivolumab plus ipilimumab. In the second experimental arm, patients received a combination of nivolumab plus the chemotherapy combination of cisplatin and fluorouracil. In the third line, patients received the chemotherapy combination alone. The study had the primary outcomes of overall survival (OS) and progression-free survival (PFS) in patients with PD-L1-expressing tumors. Secondary outcomes included objective response rate (ORR), as well as OS and PFS in all randomized patients.
In order to participate patients must be 18 years old or older, have esophageal cancer that cannot be operated on or treated with definitive chemoradiation with curative intent, and must agree to provide tumor tissue samples. Patients with tumor cells in the brain or spinal cord or any active known or suspected autoimmune disease are not eligible to participate.
The data from CheckMate-648 builds upon the phase 3 CheckMate-649 (NCT02872116) trial, which compared the efficacy of nivolumab plus ipilimumab or nivolumab plus chemotherapy against chemotherapy alone in stomach cancer or stomach esophagus junction cancer. The study has an estimated enrollment of 2032 participants and an estimated completion date of October 2022.
CheckMate-649 is split into 5 arms. In arm 1, patients received a combination of nivolumab and ipilimumab. In arm 2, patients received a chemotherapy combination of oxaliplatin plus capecitabine (XELOX). In arm 3, patients received the chemotherapy combination of oxaliplatin, leucovorin, and fluorouracil (FOLFOX). In arm 4, patients received nivolumab plus XELOX. In arm 5 patients received nivolumab plus FOLFOX.
The primary outcomes of the study were OS and PFS. Secondary outcomes included ORR and time to symptom deterioration. In order to participate, patients must be 18 years old or older and have not received neoadjuvant or adjuvant therapy for their disease within the last 6 months. Those with the presence of tumor cells in the brain or uncontrolled medical disorders are not eligible to participate.
Of the 1581 participants randomized into the nivolumab plus chemotherapy and chemotherapy alone arms, nivolumab plus chemotherapy showed greater improvements in OS and PFS versus chemotherapy alone in patients whose tumor’s expressed PD-1 CPS ≥ 5. The OS hazard ratio (HR) was 0.71 (98.4% CI 0.59-0.86; P <.0001) and there was PFS benefit (HR, 0.68; 98% CI, 0.56-0.81; P <.0001).2
“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,” said Ian M. Waxman, MD, development lead of gastrointestinal cancers at Bristol Myers Squibb, 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.”