Pembrolizumab plus carboplatin and paclitaxel as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma
To date, the standard first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) consists of pembrolizumab plus platinum and 5-fluorouracil (5-FU), regardless of PD-L1 status.. In Keynote-B10, also pembrolizumab plus carboplatin and paclitaxel showed antitumor activity with a manageable safety profile. These findings suggest that this 5-FU-free regimen may be comparable to the current first-line standard-of-care and may expand treatment options for these patients.
Based on the results of the pivotal Keynote-048 study, pembrolizumab combined with platinum and 5-FU is approved for the first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Because of toxicities, patient inconvenience, costs and complications associated with continuous 4-day infusion, alternatives to 5-FU are needed. Therefore, the ongoing, global, open-label, phase IV Keynote-B10 study investigates pembrolizumab in combination with carboplatin and paclitaxel as first-line treatment for patients with R/M HNSCC.
Study design
In the ongoing phase IV Keynote-B10 trial, patients with previously untreated, R/M HNSCC of oral cavity, oropharynx, larynx or hypopharynx, regardless of tumour PD-L1 status and with an ECOG PS 0/1 received pembrolizumab (200 mg Q3W), carboplatin (AUC 5 mg/mL/min Q3W), and paclitaxel (175 mg/m2 Q3W on day 1 or 100 mg/m2 Q1W on days 1 and 8). Treatment continued for ≤35 cycles of pembrolizumab, ≤6 cycles of carboplatin and paclitaxel, or until disease progression, unacceptable toxicity, or patient withdrawal. Primary endpoint was objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR) and progression-free survival by BICR, overall survival, safety and tolerability. The efficacy analysis was based on the first 82 treated patients to ensure sufficient follow-up. Safety was analysed in all treated patients.
Results
At the data cut-off on March 16 2022, 92 of 100 planned patients were enrolled. At that time, 41 patients remained on treatment and 51 discontinued, mostly because of disease progression (N= 31) or adverse events (N= 10). The median age of study participants was 64 years, with the majority being male (82.6%) and White (87.0%). Most patients received the three-weekly paclitaxel regimen (77.2%) and less than 20% of patients had PD-L1 negative tumours. After a median follow-up of 8.2 months, the confirmed ORR was 42.7%, including four complete responses (4.9%). The median time to response was 1.5 months and the disease control rate was 58.5%. The median duration of response was 5.5 months. In total, 86.3% of patients experienced any reduction in tumour size from baseline, with 64.3% reporting ≥30% reduction. Importantly, responses were seen regardless of PD-L1 status and regardless of the investigator’s choice of paclitaxel regimen. The median number of cycles for carboplatin and paclitaxel was 5.0, while it was 6.0 for pembrolizumab. For all treated patients (N = 92), any-grade treatment-related adverse events (TRAEs) occurred in 95.7% of patients. Grade 3-5 TRAEs were reported in 70.7% of patients and serious TRAEs occurred in 17.4% of patients. The most common grade ≥3 TRAEs were decreased neutrophil count (43.5%), anaemia (19.6%), and white blood cell count decrease (17.4%). Two grade 5 chemotherapy-related serious AEs occurred, one due to sepsis and one due to a hypersensitivity reaction. The majority of immune-mediated AEs and infusion reactions were of low grade.
Conclusion
This first global, prospective trial of combination pembrolizumab, carboplatin and paclitaxel demonstrated anti-tumour activity in first-line R/M HNSCC. In addition, the safety profile of this combination was consistent with the known safety profiles of each therapy and manageable with supportive care. Efficacy and safety results of Keynote-B10 may thus suggest this 5-FU-free chemotherapy combination with pembrolizumab may be an alternative to current SOC and may expand treatment options for first-line R/M HNSCC, irrespective of PD-L1 status.
Reference
Dzienis M, et al. Pembrolizumab (pembro) + carboplatin (carbo) + paclitaxel (pacli) as first-line (1L) therapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Phase VI KEYNOTE-B10 study. Presented at ESMO 2022; Abstract 651O.
