Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial

Abstract

Purpose: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).

Methods: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator's choice of paclitaxel 100 mg/m² on days 1 and 8 or 175 mg/m² on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR.

Results: Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals.

Conclusion: Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.

FIG 1.

Trial profile. ^aReasons are not exclusive (ie, one patient can meet more than one criterion). ^bProgressive disease includes patients who experienced clinical progression or radiographic progressive disease. BICR, blinded independent central review; ECOG PS, Eastern Cooperative Oncology Group performance status; R/M HNSCC, recurrent/metastatic head and neck squamous cell carcinoma

FIG 2.

Subgroup analysis of confirmed objective response per RECIST v1.1 by BICR. BICR, blinded independent central review; CPS, combined positive score; ECOG PS, Eastern Cooperative Oncology Group performance status; HPV, human papilloma virus; ORR, objective response rate; q1w, once a week; q3w, once every 3 weeks.

FIG 3.

Kaplan-Meier estimates of (A) duration of response and (B) progression-free survival, per RECIST v1.1 by BICR, and (C) overall survival. Median follow-up: 18.9 months (range, 9.1-27.0). BICR, blinded independent central review.

FIG A1.

(A) Maximum change from baseline in target lesion size (Includes 91 patients with at least one baseline and postbaseline assessment) and (B) time to response in patients with a confirmed objective response per RECIST v1.1 by BICR. BICR, blinded independent central review.

FIG A2.

Kaplan-Meier estimates of duration of response per RECIST v1.1 by investigator assessment.