Pembrolizumab Plus Chemo Elicits Responses in Head and Neck Squamous Cell Carcinoma

The first-line combination of pembrolizumab (Keytruda), carboplatin, and paclitaxel demonstrated antitumor activity and a manageable toxicity profile when administered to patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to data from the phase IV KEYNOTE-B10 study (NCT04489888) published in the Journal of Clinical Oncology.¹

The regimen (n = 101) induced a confirmed objective response rate (ORR) of 49% (95% CI, 38.4%-58.7%) by blinded independent central review (BICR) and RECIST 1.1 criteria; this was comprised of a 7% complete response (CR) rate and a 42% partial response rate. The disease control rate achieved with the combination was 75% (95% CI, 65.7%-83.3%).

“In summary, pembrolizumab in combination with paclitaxel and carboplatin resulted in durable antitumor activity and efficacy consistent with other first-line regimens in this patient population, including the standard-of-care combination of pembrolizumab plus platinum and FU from KEYNOTE-048 [NCT02358031]. Safety was manageable and comparable with the combination regimens without FU,” lead study author Marcin Dzienis, MD, of the Cancer Department at Gold Coast University Hospital, Southport, QLD, Australia, and colleagues, wrote in the paper. “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 recurrent/metastatic HNSCC, regardless of PD-L1 status.”

The single-arm, open-label, multicenter study enrolled patients with histologically or cytologically confirmed, recurrent or metastatic HNSCC that is not curable with local therapies. They were required to be at least 18 years of age who did not receive prior systemic therapy in the recurrent or metastatic setting. They had measurable disease by RECIST 1.1 criteria and an ECOG performance status of 0 or 1. Their primary tumors needed to be located in the oropharynx, oral cavity, hypopharynx, or larynx.

Investigators administered 200 mg of pembrolizumab intravenously (IV) once every 3 weeks plus area under the curve 5 mg/mL/min of IV carboplatin on day 1 once every 3 weeks, and investigator’s choice of IV paclitaxel at 100 mg/m2 on days 1 and 8 once every 3 weeks or 175 mg/m2 on day 1 once every 3 weeks.

ORR by BICR and RECIST v1.1 criteria served as the study’s primary end point, and key secondary end points comprised duration of response (DOR), BICR-assessed progression-free survival (PFS) per RECIST v1.1 criteria, overall survival (OS), and safety. All efficacy end points were also evaluated by investigator assessment.

The median patient age was 64.0 years (range, 29-89), with 46% of patients aged 65 years or older. Most patients were male (84%),White (87%), had an ECOG performance status of 1 (60%), and stage IV disease (92%). Half of patients received treatment in North America and the other half received treatment in other parts of the world, including Argentina, Australia, and Brazil. With regard to paclitaxel dose, 76% received the agent at 175 mg/m2 and the remaining 24% received it at 100 mg/m2.

Eighty percent of patients had a PD-L1 combined positive score (CPS) of 1 or higher, 20% had a CPS below 1, and 41% had a CPS of at least 20. The most common primary tumor location was the oropharynx (45%), followed by the oral cavity (27%), the larynx (24%), and the hypopharynx (5%). Twenty-three percent of patients were positive for human papillomavirus (HPV) in the oropharynx; 22% and 55% of patients were HPV negative in the oropharynx and nonoropharynx, respectively. Disease presented as recurrent (32%), metastatic (31%), or both (38%). Metastatic disease sites included the lung (54%), live (13%), other (13%), lymph node (11%), mediastinum (11%), pleura (6%), skin (5%), abdominal cavity (2%), adrenal gland (2%), brain (2%), and vertebral column (1%).

All 101 patients who were assigned to treatment received at least 1 dose. At the data cutoff date of February 20, 2023, 15 patients remained on treatment. Reasons for discontinuation included disease progression (n = 55), toxicity (n = 18), clinical progression (n = 7), receipt of non-study anticancer therapy (n = 3), and patient withdrawal (n = 3).

Additional efficacy findings revealed that 70% of patients who had at least 1 post-baseline assessment (n = 91) experienced a target lesion size reduction of 30% or more. Moreover, antitumor activity observed with the regimen were generally consistent across subgroups. Specifically, the confirmed ORRs in those with a PD-L1 CPS less than 1, in those with HPV-positive oropharynx tumors, and those with HPV-negative oropharynx tumors were 65% (95% CI, 40.8%-84.6%), 65% (95% CI, 42.7%-83.6%), and 50% (95% CI, 28.2%-71.8%), respectively. The median time to response (TTR) in those with a confirmed CR (n = 49) was 1.5 months (range, 1.1-6.8).

Moreover, the median DOR was 5.5 months (95% CI, 4.2-6.7) by BICR and RECIST 1.1 criteria. Approximately 21% of patients achieved a CR or PR that persisted for at least 1 year.

The investigator-assessed confirmed ORR with the pembrolizumab/chemotherapy combination was 50% (95% CI, 39.4%-59.6%), and this included a confirmed CR rate of 8%. The DCR by investigator assessment was 75% (95% CI, 65.7%-83.3%). The median investigator-assessed TTR and DOR with the combination was 1.5 months (range, 1.1-5.6) and 6.9 months (range, 5.4-8.2). Twenty-seven percent of patients with a CR or PR were estimated to have a response that lasted or at least 1 year.

The median PFS was 5.6 months (95% CI, 5.1-6.7) by BICR and RECIST 1.1 criteria; the estimated 12-month PFS rate was 12% (95% CI, 6.3%-20.0%). The median OS was 13.1 months (95% CI, 9.6-15.2), and the estimated 12-month OS rate was 52% (95% CI, 42.1%-61.5%).

Regarding safety, 95% of patients experienced treatment-related adverse effects (TRAEs). The most common TRAEs included decreased neutrophil count (grade 1/2, 13%; grade 3, 19%; grade 4, 26%), fatigue (38%; 6%; 0%), anemia (24%; 19%; 1%), alopecia (33%; 1%; 0%), decreased platelet count (19%; 10%; 1%), decreased white blood cell count (12%; 9%; 8%), nausea (24%; 4%; 0%), diarrhea (18%; 5%; 0%), reduced appetite (20%; 1%; 0%), decreased lymphocyte count (11%; 8%; 1%), hypothyroidism (17%; 0%; 0%), constipation (16%; 0%; 0%), weight decrease (15%; 1%; 0%), and hypomagnesemia (14%; 1%; 0%), among others.

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