First-Line Pembrolizumab Plus Chemotherapy Showed Promise Among Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Results from the KEYNOTE-B10 Trial  

According to results from the phase 4 KEYNOTE-B10 trial, first-line pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity with a manageable safety profile among patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). 

“Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma is pembrolizumab plus platinum and fluorouracil,” stated Marcin Dzienis, MD, Gold Coast University Hospital, Southport, Queensland, Australia, and coauthors. “However, fluorouracil is associated with potential challenges creating a clinical need for alternative chemotherapy combinations.” 

In this single-arm, open-label study, 101 patients with previously untreated histologically or cytologically confirmed HNSCC, regardless of PD-L1 status, were assigned to receive 200 mg of pembrolizumab every 3 weeks for ≤ 35 cycles plus AUC 5 mg/mL/min of carboplatin once every 3 weeks for ≤ 6 cycles and investigator’s choice 100 mg/m² of paclitaxel (days 1 and 8) or 175 mg/m² (on day 1) every 3 weeks. The primary end point was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 18.9 months, with 7 complete responses and 42 partial responses, confirmed ORR was 49% in the intention-to-treat population and 65% in patients with PD-L1 <1. Disease control rate was 75% overall, with 70% of patients achieving at least 30% reduction in target lesion size. Median DOR was 5.5 months and an estimated 21% of patients had a complete or partial response lasting at least 12 months. Median PFS was 5.6 months and estimated 12-month PFS rate was 12%. Median OS was 13.1 months and estimated 12-month OS rate was 52%. 

Grade ≥3 treatment-related adverse events occurred in 75% (n = 76) of patients and most frequently included neutrophil count decrease (45%), anemia (20%), white blood cell count decrease (17%), and platelet count decrease (11%). Twenty-seven patients experienced serious treatment-related adverse events, and 3 patients died due to events deemed as possibly treatment-related by the investigator (hypersensitivity, sepsis, and death). 

As Dr Dzienis et al concluded, “Pembrolizumab in combination with paclitaxel and carboplatin resulted in durable antitumor activity and efficacy consistent with other first-line regimens in this patient population.”

Journal of Clinical Oncology Associate Editor Maura Gillison, MD, PhD, MD Anderson Cancer Center, Houston, Texas, added KEYNOTE-B10 “provides some support for the common practice of substituting a taxane for [fluorouracil] in patients treated with chemo immunotherapy in the first-line for recurrent or metastatic HNSCC.”

Source:

Dzienis M, Cundom J, Fuentes CS, et al. 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. J Clin Oncol. Published online: July 22, 2024. doi: 10.1200/JCO.23.02625