Immunotherapy with nivolumab (Opdivo) is now approved in the United States for first-line use in the treatment of unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
The new approval for the drug, a programmed cell death ligand-1 (PD-L1) inhibitor, is for use in this patient population regardless of PD-L1 status.
the indication also specifies that nivolumab is to be used together with chemotherapy (with a fluoropyrimidine- and platinum-containing regimen) or in combination with ipilimumab (Yervoy), an immunotherapy with a different mechanism of action.
“Today’s approvals bring two first-line immunotherapy-based treatment options at once…to newly diagnosed patients with unresectable advanced or metastatic ESCC,” commented Adam Lenkowsky, a senior vice president at Bristol Myers Squibb, which makes both nivolumab and ipilimumab.
The approval of the new indication by the US Food and Drug Administration was based on improved survival shown in the phase 3 CheckMate-648 trial, which involved nearly 1000 patients. The trial had three arms and compared nivolumab plus chemotherapy (n = 321) and nivolumab plus ipilimumab (n = 324) with chemotherapy alone (n = 324).
The results showed improved survival with both nivolumab combinations compared with chemotherapy (fluorouracil and cisplatin) alone. Overall survival was improved both in all randomized patients (a secondary endpoint) and in patients whose tumors expressed PD-L1 (≥ 1%), the primary endpoint.
For the combination of nivolumab plus chemotherapy, median overall survival was 13.2 versus 10.7 months compared with chemotherapy alone in all randomized patients and 15.4 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
For the combination of nivolumab plus ipilimumab, median overall survival was 12.8 versus 10.7 months with chemotherapy alone in all randomized patients and 13.7 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
However, progression-free survival did not reach statistical significance in any group.
“Unresectable advanced or metastatic ESCC is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting,” commented Jaffer A. Ajani, MD, professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center in Houston. He was also the lead US investigator for CheckMate-648 and, in a company press release, said the “two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”
Results from the trial were presented last year at the American Society of Clinical Oncology (ASCO) 2021 annual meeting. At that time, trial investigator Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital in Sutton, United Kingdom, told attendees that “nivolumab plus chemotherapy and nivolumab plus ipilimumab each represent a new potential first-line standard of care for patients with advanced ESCC.”
Commenting on that presentation, Samuel J. Klempner, MD, a gastrointestinal medical oncologist at the Massachusetts General Hospital Cancer Center, Boston, noted that the “prospect of a chemo-free regimen for advanced ESCC with the well-studied combination of ipilimumab and nivolumab would represent a welcome addition to our treatment armamentarium.”
No New Safety Signals
Chau noted there were no new safety signals with either of the immunotherapies.
Nivolumab and/or chemotherapy were discontinued in 39% of patients and delayed in 71% of patients for an adverse reaction.
Nivolumab and/or ipilimumab were discontinued in 23% of patients and delayed in 46% of patients for an adverse reaction.
The manufacturer cautions that immunotherapy with nivolumab with or without ipilimumab has been associated with severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, and infusion-related reactions.