|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Two nivolumab-based regimens — nivolumab plus chemotherapy and nivolumab plus ipilimumab — improved overall survival (OS), when compared with chemotherapy alone, in patients with advanced esophageal squamous cell carcinoma (ESCC), according to first results from the CheckMate 648 trial.
The results were presented as a late-breaking abstract at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Ian Chau, MD, of The Royal Marsden Hospital in London and Surrey, UK, and colleagues.
“Esophageal cancer carries a very heavy global cancer burden, accounting for over half a million deaths per year,” Dr. Chau said during a press briefing ahead of the meeting. “In 2020, for every 10 patients diagnosed with this disease, 9 patients would have died.”
The phase 3 CheckMate 648 trial (ClinicalTrials.gov Identifier: NCT03143153) enrolled patients with unresectable advanced, recurrent, or metastatic ESCC who had received no prior systemic treatment for advanced disease.
Patients were randomized and stratified by several factors into 1 of 3 study arms — chemotherapy alone (fluorouracil plus cisplatin; n = 324), nivolumab plus chemotherapy (n = 321), or nivolumab plus ipilimumab (n = 325).
The study’s coprimary endpoints were OS and progression-free survival (PFS) in patients with programmed cell death-ligand 1 (PD-L1) expression of 1% or higher. OS and PFS in the all-randomized population were secondary endpoints.
The minimum follow-up at the data cutoff was 12.9 months.
Results showed that nivolumab plus chemotherapy improved OS compared with chemotherapy alone. Among patients with PD-L1 expression of 1% or higher, the median OS was 15.4 months with nivolumab plus chemotherapy and 9.1 months with chemotherapy alone (hazard ratio [HR], 0.54; P <.0001). In the all-randomized population, the median OS was 13.2 months and 10.7 months, respectively (HR, 0.74; P =.0021).
Nivolumab plus ipilimumab also showed superior OS compared with chemotherapy alone. Among patients with PD-L1 expression of 1% or higher, the median OS was 13.7 months with nivolumab plus ipilimumab and 9.1 months with chemotherapy (HR, 0.64; P =.0010). In the all-randomized population, the median OS was 12.8 months and 10.7 months, respectively (HR, 0.78; P =.0110).
Compared with chemotherapy alone, PFS was improved in the nivolumab- chemotherapy arm among patients with PD-L1 expression of 1% or higher (HR, 0.65; 95% CI, 0.46-0.92). However, PFS was not improved among patients who received nivolumab plus chemotherapy in the all-randomized population (HR, 0.81; 95% CI, 0.64-1.04).
Likewise, PFS was not improved with nivolumab plus ipilimumab, either in the all-randomized population (HR, 1.26; 95% CI, 1.04-1.52) or in patients with PD-L1 expression of 1% or higher (HR, 1.02; 95% CI, 0.73-1.43).
The rate of grade 3/4 treatment-related adverse events was in 47% in the nivolumab-chemotherapy arm, 32% in the nivolumab-ipilimumab arm, and 36% in the chemotherapy-alone arm. No new safety signals were seen in the nivolumab-containing arms.
Dr Chau concluded that each nivolumab-containing combination “represents a new potential first-line standard of care for patients with advanced esophageal squamous cell carcinoma, based on the results from CheckMate 648, the largest randomized controlled trial conducted in this disease setting to date.”
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Chau I, Doki Y, Ajani JA, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study. J Clin Oncol. 2021;39: (suppl 15; abstr LBA4001). doi: 10.1200/JCO.2021.39.15_suppl.LBA4001