KEY TAKEAWAYS
- Phase 2 KEYNOTE-048 trial evaluated pembrolizumab ± chemo as a 1L treatment for R/M HNSCC.
- The trial’s primary aim was to assess OS and PFS outcomes.
- The study was conducted on Japanese patients with a CPS score of PD-L1 ≥ 20 and ≥ 1.
- Pembrolizumab showed superior OS outcomes in the CPS ≥ 20 subgroups compared to EXTREME (median of 28.2 months versus 13.3 months).
- Pembrolizumab-chemotherapy demonstrated comparable OS outcomes to EXTREME in all subgroups.
- Pembrolizumab and pembrolizumab-chemotherapy had lower treatment-related adverse events in grades 3-5 than EXTREME.
The findings of the Japanese cohort in the phase 3 KEYNOTE-048 trial evaluated pembrolizumab monotherapy, pembrolizumab in combination with platinum and 5-fluorouracil chemotherapy, or cetuximab in combination with platinum and 5-fluorouracil chemotherapy (EXTREME regimen) for previously untreated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The study’s primary endpoints were overall survival (OS) and progression-free survival (PFS). The assessment of effectiveness was conducted on individuals diagnosed with a combined positive score (CPS) of PD-L1 ≥ 20 and ≥ 1, as well as the entire subgroup of Japanese patients (n = 67). At the data cutoff on February 25th, 2019, it was observed that in the PD-L1 CPS ≥ 20 subgroups, pembrolizumab resulted in a longer overall survival compared to EXTREME (with a median of 28.2 months versus 13.3 months and a hazard ratio of 0.29 [95% CI 0.09-0.89]).
Pembrolizumab resulted in similar overall survival in the total Japanese population and CPS ≥ 1 subgroups (with a median of 23.4 months versus 13.6 months and a hazard ratio of 0.51 [95% CI 0.25-1.05] and a median of 22.6 months versus 15.8 months and a hazard ratio of 0.66 [95% CI 0.31-1.41], respectively). The use of Pembrolizumab-chemotherapy resulted in a comparable overall survival (OS) outcome to that of EXTREME in patients with a PD-L1 CPS score of ≥ 20 (with a median of 18.1 months versus 15.8 months and a hazard ratio (HR) of 0.72 [95% CI 0.23-2.19]), CPS score of ≥ 1 (with a median of 12.6 months versus 15.8 months and an HR of 1.19 [95% CI 0.55-2.58]), and in the total Japanese subgroups (with a median of 12.6 months versus 13.3 months and an unadjusted HR of 1.10 [95% CI 0.55-2.22]).
The median progression-free survival (PFS) demonstrated no significant difference between administering pembrolizumab and pembrolizumab-chemotherapy compared to EXTREME across all subgroups. In patients who received pembrolizumab, pembrolizumab-chemotherapy, and EXTREME, treatment-related adverse events in grades 3-5 were 22%, 76%, and 89%, respectively. A fatal case of treatment-associated pneumonitis was observed in a patient undergoing pembrolizumab chemotherapy. The findings support the administration of pembrolizumab as the primary treatment option, either alone or in combination with chemotherapy, among Japanese patients diagnosed with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Source: https://pubmed.ncbi.nlm.nih.gov/36264378/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02358031
Takahashi S, Oridate N, Tanaka K, Shimizu Y, Fujimoto Y, Matsumoto K, Yokota T, Yamazaki T, Takahashi M, Ueda T, Hanai N, Yamaguchi H, Hara H, Yoshizaki T, Yasumatsu R, Nakayama M, Shiga K, Fujii T, Mitsugi K, Takahashi K, Nohata N, Gumuscu B, Swaby RF, Tahara M. First-line pembrolizumab ± chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048. Int J Clin Oncol. 2022 Dec;27(12):1805-1817. doi 10.1007/s10147-022-02233-6. Epub 2022 Oct 20. PMID: 36264378; PMCID: PMC9700657.
