Pembrolizumab/Paclitaxel Offers Alternative to Standard Treatment in Head and Neck Cancer

Head and neck cancer image: © CLIPAREA.com- stock.adobe.comHead and neck cancer image: © CLIPAREA.com- stock.adobe.com

The addition of pembrolizumab (Keytruda) to carboplatin and paclitaxel for the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) showed promising results in the phase 4 KEYNOTE-B10 study(NCT04489888), presenting an alternative treatment option than the standard-of-care of pembrolizumab plus platinum and fluorouracil (FU) in this patient population.

With a median follow-up of 18.9 months (range, 9.1-27.0), there was an objective response rate (ORR) of 49% (n = 49; 95% CI, 38.4%-58.7%) with a 7% (n = 7) complete response (CR) rate. Three of the patients who achieved a CR had an ongoing response at the time of data cutoff, and 21% of patients achieved a CR or partial response with a duration of at least 12 months. The disease control rate was 75% (n = 76; 95% CI, 65.7%-83.3%).

Response rates were equally promising among patient subgroups. In patients with expression of PD-L1 < 1, the ORR was 65% (95% CI, 40.8%-84.6%). The ORR was 65% (95% CI; 42.7%-84.6%) in patients with a human papillomavirus (HPV)-positive tumor and 50% (95% CI, 28.2%-71.8%) in those with an HPV-negative tumor.

The median progression-free survival (PFS) was 5.6 months (95% CI, 5.1-6.7) with an estimated 12-month PFS rate of 12% (95% CI, 6.3%-20.0%). Median overall survival (OS) was 13.1 months (95% CI, 9.6-15.2) with an estimated 12-month OS rate of 52% (95% CI, 42.1%-61.5%).

“5-FU is still a valid treatment option. This study was more to allow clinicians and patients to have access to an added option that may be suitable based on patient preferences or comorbidities. [Overall], this increases options for patients rather than replaces anything we currently have,” explained Marcin Dzienis, MD, study author, in an interview with Targeted Oncology^TM.

“Before commencing KEYNOTE-B10, limited clinical data were available for PD-1 inhibitors in combination with a platinum and paclitaxel in head and neck cancers, and no data had been published from a prospective clinical trial in first-line R/M HNSCC,” authors wrote in the study published in the Journal of Clinical Oncology.

For many patients, FU is linked with cardiovascular and gastrointestinal toxicities, highlighting the need for a safe and effective alternative. Additionally, FU has a 4-day continuous intravenous infusion, which is inconvenient for patients and associated with higher medical costs.

In KEYNOTE-048 (NCT02358031), which led to the approval of pembrolizumab plus platinum-based and FU chemotherapy, the ORR with the combination was 36%, with 6% of patients achieving a CR, which are numerically lower than what was observed in KEYNOTE-B10 with 49% and 7%, respectively.

Regarding safety, 95% of patients experienced treatment-related adverse events (TRAEs). The most common TRAEs were decreased neutrophil count (57%), anemia (44%), fatigue (44%), and alopecia (34%). Gastrointestinal AEs were reported in 54% of patients and were most commonly nausea (28%), diarrhea (23%), constipation (16%), and vomiting (15%). Serious TRAEs were observed in 27% of patients, and 13 patients died due to AEs of any cause; 3 events could be considered related to treatment, including hypersensitivity and sepsis.

Comparatively, in KEYNOTE-048, gastrointestinal AEs were reported in 67% of patients, while 37% of patients experienced serious TRAEs, and 11 patients died from treatment-related causes.

“Results from KEYNOTE-B10 support the use of pembrolizumab in combination with paclitaxel and carboplatin as an additional first-line treatment option in patients with R/M HNSCC, regardless of PD-L1 status,” concluded study authors.

REFERENCE:

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