KEY TAKEAWAYS
- The phase 3 KEYNOTE-048 trial aimed to assess the long-term efficacy and PFS2 of pembrolizumab and pembrolizumab-chemotherapy as second-line therapy for recurrent/metastatic head and neck squamous cell carcinoma.
- Patients were randomly assigned to receive pembrolizumab, pembrolizumab, or ccetuximab chemotherapy.
- Pembrolizumab improved OS in patients with PD-L1 CPS ≥ 20 and CPS ≥ 1, and it was non-inferior in the total population.
- Pembrolizumab-based therapy showed long-term survival benefits in recurrent/metastatic head and neck squamous cell carcinoma, with a good response to subsequent treatment.
In KEYNOTE-048, pembrolizumab and pembrolizumab-chemotherapy showed efficacy against recurrent/metastatic head and neck squamous cell carcinoma. A post hoc analysis of long-term efficacy and progression-free survival (PFS2) on second-line therapy was presented. Pembrolizumab, pembrolizumab-chemotherapy, and cetuximab-chemotherapy were randomly assigned (1:1:1) to patients. Efficacy was evaluated in populations with combined positive scores (CPS) ≥ 20, CPS ≥ 1, and total populations, with no adjustment for multiplicity or alpha. The median duration of study follow-up was 45,0 months (interquartile range, 41,0 to 49,2 months; n = 882). Pembrolizumab improved overall survival in the PD-L1 CPS ≥20 (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.46 to 0.81) and CPS≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was non-inferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97) as of the data cutoff date (18 February 2020).
Pembrolizumab-chemotherapy enhanced overall survival in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS 1 (HR, 0.64; 95% CI, 0.53 to 78), and total (HR, 0.71) populations. The second-course pembrolizumab objective response rate was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was comparable following pembrolizumab and longer following pembrolizumab-chemotherapy for next-line taxanes but shorter following pembrolizumab and comparable following pembrolizumab-chemotherapy for next-line nontaxanes. After four years of follow-up, Pembrolizumab-chemotherapy continued outperforming cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Following therapy with pembrolizumab, patients responded well to subsequent treatments.
Source: https://pubmed.ncbi.nlm.nih.gov/36219809/
Clinical Trial: http://clinicaltrials.gov/show/NCT02358031
Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol. 2023 Feb 1;41(4):790-802. doi: 10.1200/JCO.21.02508. Epub 2022 Oct 11. PMID: 36219809; PMCID: PMC9902012.
