As reported in the Journal of Clinical Oncology by Marcin Dzienis, MD, and colleagues, the phase IV KEYNOTE-B10 trial of pembrolizumab plus carboplatin and paclitaxel in the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) showed that the regimen produced clinically meaningful activity.
Marcin Dzienis, MD
As stated by the investigators, “Standard-of-care first-line treatment for recurrent/metastatic HNSCC is pembrolizumab plus platinum and fluorouracil. However, fluorouracil 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.”
Study Details
In the study, 101 patients enrolled between October 2020 and April 2022 from sites in Argentina, Australia, Brazil, Canada, and the United States received pembrolizumab at 200 mg every 3 weeks for ≤ 35 cycles, carboplatin at AUC 5 every 3 weeks for ≤ 6 cycles, and investigator’s choice of paclitaxel at 100 mg/m2 on days 1 and 8 or 175 mg/m2 on day 1 every 3 weeks.
The primary outcome measure of the study was objective response rate on blinded independent central review.
Key Findings
Median follow-up was 18.9 months (range = 9.1–27.0 months). Objective response was observed in 49 (49%, 95% confidence interval [CI] = 38.4%–58.7%) of 101 patients, including complete response in 7 (7%). An additional 27 patients (27%) had stable disease; the disease control rate was 75%.
Median time to response was 1.5 months (range = 1.1–6.8 months). Median duration of response was 5.5 months (95% CI = 4.2–6.7 months), with 21% of responses lasting ≥ 12 months.
Median progression-free survival was 5.6 months, with a 12-month rate of 12%. Median overall survival was 13.1 months, with a 12-month rate of 52%.
No new safety signals were observed. Grade ≥ 3 treatment-related adverse events occurred in 75% of patients, the most common being decreased neutrophils (in 45%), anemia (in 20%), and decreased white blood cells (in 17%). Serious treatment-related adverse events occurred in 27%, most commonly febrile neutropenia (in 5%), pneumonia (in 4%), and decreased neutrophils (in 4%). Death considered possibly related to treatment occurred in three patients, with causes including hypersensitivity and sepsis.
The investigators concluded, “Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line recurrent/metastatic HNSCC, suggesting this combination may be an alternative option for this patient population.”
Dr. Dzienis, of the Cancer Department, Gold Coast University Hospital, Southport, QLD, Australia, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
