In patients with relapsed or metastatic head and neck squamous cell carcinoma, a regimen of the immune checkpoint inhibitor pembrolizumab plus carboplatin and paclitaxel, evaluated in the phase IV KEYNOTE-B10 trial, demonstrated antitumor activity, with a good safety profile, investigators reported at the European Society for Medical Oncology (ESMO) Congress 2022.1
“This fluorouracil-free regimen may be comparable to the historical first-line standard of care and may expand our treatment options for first-line relapsed or metastatic head and neck squamous cell carcinoma,” said Marcin Dzienis, MD, of Gold Coast University Hospital in Southport, Queensland, Australia, who presented the study’s initial results.
Marcin Dzienis, MD
The current first-line standard of care for relapsed or metastatic head and neck squamous cell carcinoma, regardless of PD-L1 status, is pembrolizumab plus platinum and fluorouracil. Alternatives to fluorouracil are needed because of the cardiovascular risks, potential toxicities associated with dihydropyrimidine dehydrogenase deficiency, patient inconvenience, costs, and complications associated with continuous 4-day infusions of the drug, according to Dr. Dzienis.
Clinical studies have shown platinum plus paclitaxel to be no less effective than platinum plus fluorouracil in this malignancy. The open-label KEYNOTE-B10 trial is the first global prospective study of carboplatin plus paclitaxel with the addition of pembrolizumab.
In the ongoing KEYNOTE-B10 trial, patients with previously untreated, relapsed or metastatic head and neck squamous cell carcinoma and any expression of tumor PD-L1 received pembrolizumab at 200 mg every 3 weeks, carboplatin AUC 5 mg/mL/min intravenously (IV) every 3 weeks, and paclitaxel at 175 mg/m2 IV every 3 weeks or 100 mg/m2 IV weekly on days 1 and 8. Treatment was continued up to 35 cycles of pembrolizumab and 6 cycles of chemotherapy.
The primary endpoint was objective response rate by blinded independent central review. The efficacy analysis was based on the first 82 treated patients, to ensure sufficient follow-up. Safety was analyzed in all treated patients.
At a median follow-up of 8.2 months, the confirmed objective response rate was 42%, with 5% being complete responses. The disease control rate was 72%. By PD-L1 status, 18.5% of patients who had a combined positive score (CPS) of less than 1 achieved a response (64%). Among patients with a CPS of at least 1, 38% responded; for those with a CPS of at least 20, responses were seen in 34%. There was no apparent difference in response between the two paclitaxel dosing schedules, Dr. Dzienis reported. More than 86% of evaluable patients achieved some reduction in target lesions from baseline, and 64% had at least a 30% reduction in size. Median duration of response was 5.5 months, median progression-free survival was 5.6 months, and median overall survival was 12.1 months. At 12 months, 58% of patients remained alive.
For all 92 treated patients, any-grade treatment-related adverse events occurred in 96%. Grade 3 to 5 toxicities were observed in 71% of patients, with two deaths from sepsis and hypersensitivity reaction. The most common treatment-related grade ≥ 3 adverse events were decreased neutrophil count (43%), anemia (20%), and decreased white blood cell count (17%).
DISCLOSURE: Dr. Dzienis reported financial relationships with Merck Sharp & Dohme, Novartis, and Bristol Myers Squibb.
1. Dzienis MR, Cundom JE, Fuentes CS, et al: Pembrolizumab plus carboplatin plus paclitaxel as first-line therapy in recurrent/metastatic head and neck squamous cell carcinoma: Phase VI KEYNOTE-B10 study. ESMO Congress 2022. Abstract 651O. Presented September 12, 2022.