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Final results of the phase 3 CheckMate 651 trial did not reveal a statistically significant improvement in overall survival (OS) with nivolumab plus ipilimumab compared with cetuximab, cisplatin or carboplatin, and fluorouracil (EXTREME regimen) in the frontline treatment of patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).
Although the CheckMate 651 trial (ClinicalTrials.gov Identifier: NCT02741570) did not meet its primary endpoints, the combination of nivolumab plus ipilimumab showed a positive trend towards OS in a subset of patients whose tumors expressed PD-L1 with a combined positive score (CPS) greater than or equal to 20 or CPS greater than or equal to 1.
Additionally, nivolumab plus ipilimumab tended to delay symptom deterioration and improved the overall health status compared with EXTREME in the subset of patients with CPS greater than or equal to 20.
The results were presented at the European Society for Medical Oncology (ESMO) Congress 2021 by Athanassios Argiris MD, PhD, FACP, of the Hygeia Hospital in Greece.
Dr Argiris commented that, “despite recent treatment advances in R/M SCCHN, durable survival benefit remains an elusive goal in patients with R/M SCCHN.”
Nivolumab and ipilimumab, which have distinct but complementary mechanisms of action, have shown survival benefits and durable responses in numerous solid tumors.
For this randomized, phase 3 trial, the research team evaluated the combination of nivolumab and ipilimumab against the EXTREME regimen as first-line treatment for platinum-eligible patients with R/M SCCHN.
The study enrolled 947 patients who were randomly assigned to receive nivolumab plus ipilimumab (472 patients) or the EXTREME regimen (475 patients).
The dual primary endpoints included OS in the all-randomized (ie, intent-to-treat) population and OS in patients whose tumors express PD-L1 with a CPS greater than or equal to 20.
The final analysis was conducted after a minimum follow-up of 27.3 months.
As compared with EXTREME, nivolumab plus ipilimumab did not show statistically significant improvements in the OS in the all-randomized population (hazard ratio [HR], 0.95; 97.9% CI, 0.80-1.13; P =.4951) or in the subset of patients with CPS greater than or equal to 20 (HR, 0.78; 97.5% CI, 0.59-1.03; P =.0469).
Researchers noted that the EXTREME control arm performed better than expected in terms of the OS based on the historical data.
In the subset of patients with CPS greater than or equal to 1, the HR for OS was 0.82 (95% CI, 0.69-0.97).
Among patients with CPS greater than or equal to 20, the median OS was prolonged with nivolumab plus ipilimumab (17.6 months; 95% CI, 13.8-22.0) compared with EXTREME (14.6 months; 95% CI, 12.3-16.0).
The 2-year progression-free survival (PFS) rate with nivolumab plus ipilimumab was 26 months compared with 16 months with EXTREME in the patients with CPS greater than or equal to 20.
Among patients with CPS greater than or equal to 1, the median OS was 15.7 months (95% CI, 13.7-18.8) with nivolumab plus ipilimumab compared with 13.2 months (95% CI, 11.1-14.6) with EXTREME.
The 2-year PFS rate was 18 months with nivolumab plus ipilimumab and 13 months with EXTREME in the patients with CPS greater than or equal to 1.
In both CPS subsets, nivolumab plus ipilimumab showed evidence of clinical benefit compared with EXTREME as seen with prolonged OS and durable responses, Dr Argiris said.
Grade 3/4 treatment-related adverse events were observed in 28% of patients who received nivolumab plus ipilimumab compared with 71% of patients treated with the EXTREME regimen.
Overall, patients who received nivolumab plus ipilimumab had a more favorable safety profile compared with the EXTREME regimen, with no new safety signals observed.
Disclosures: This research was supported by Bristol Myers Squibb (all study sites) and Ono Pharmaceuticals (study sites in Japan, Korea, and Taiwan). Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Argiris A, Harrington K, Tahara M, et al. Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA36.