KEY TAKEAWAYS
- The KEYNOTE-048 STUDY phase 3 trial aimed to investigate the optimal sequencing of pembro in PD-L1+ R/M HNSCC pts.
- Researchers noticed prolonged OS in PD-L1-positive R/M HNSCC pts receiving 1L pembro + chemo.
Pembrolizumab (pembro) and pembro + platinum + 5-FU (pembro + chemo) represented standard-of-care choices, along with cetuximab-based regimens like EXTREME (cetuximab + platinum + 5-FU) for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, the optimal sequencing of these treatments remains undefined, contingent upon PD-L1 expression and clinical considerations.
Amanda Psyrri and her team aimed to assess the overall survival (OS) outcomes in patients (pts) with PD-L1+ R/M HNSCC who underwent first-line (1L) treatment with pembro or pembro + chemo followed by cetuximab-based therapy, or EXTREME followed by immunotherapy (IO) as investigated in the KEYNOTE-048 trial.
The researchers performed an inclusive analysis on pts diagnosed with locally incurable R/M HNSCC who were randomly assigned in a 1:1:1 ratio to receive first-line (1L) pembro, pembro + chemotherapy (chemo), or the EXTREME regimen. Specifically, their post hoc exploratory analysis focused on individuals with programmed death-ligand 1 combined positive score PD-L1 CPS ≥1, who subsequently underwent second-line (2L) cetuximab-based therapy (cetux) following pembro or pembro + chemo, or 2L IO following EXTREME.
About 882 pts were enrolled, with 170 individuals having a PD-L1 CPS ≥1 and receiving 2L cetuximab or IO (1L pembro n = 63; pembro + chemo n = 37; EXTREME n = 70). The median follow-up duration was 69.3 months (mo) (range, 61.2-81.2). For pts who received pembro followed by cetuximab versus EXTREME followed by IO, the median OS (95% CI) was 15.7 mo (12.3-22.6) and 16.5 mo (13.5-19.8) respectively, with a hazard ratio (HR, 1.0; 95% CI, 0.7-1.5); 24-mo OS was 32% vs 31%.
For pts receiving pembro + chemo followed by cetuximab versus EXTREME followed by IO, the median OS (95% CI) was 22.1 mo (14.0-24.7) and 16.5 mo (11.5-19.8) respectively, with an IO (HR, 0.7; 95% CI, 0.4-1.0); 24-mo OS rates were 39% and 30%, respectively. When considering all pts who received pembro or pembro + chemo (n = 100) followed by cetuximab, the median OS was 16.6 mo (13.8-23.2), compared to 16.5 mo (13.5-19.8) for EXTREME followed by IO, with an HR of 0.9 (95% CI, 0.6-1.2); 24-mo OS rates were 34% and 31%, respectively. Among pts receiving pembro or pembro + chemo, 13 subsequently received cetuximab monotherapy, and 87 received cetuximab + chemotherapy.
The study concluded that in this post hoc exploratory analysis of KEYNOTE-048, OS was notably prolonged for pts who received pembro + chemo followed by cetuximab compared to those who underwent the EXTREME regimen followed by IO. Conversely, OS was similar for pts who received pembro followed by cetuximab versus EXTREME followed by IO. The observed differences in the use of second-line (2L) therapies across treatment arms may be attributed to clinical factors. These findings complemented the primary analysis of KEYNOTE-048, and provide support for the utilization of 1L pembro and pembro + chemo in PD-L1–positive R/M HNSCC.
The study is sponsored by Merck Sharp & Dohme LLC
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT02358031
Psyrri A, et al. (2023). “Treatment Sequencing in PD-L1-Positive Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Exploratory Analysis of the Phase 3 KEYNOTE-048 Study.” Presented at ESMO IO 2023 (Abstract 106P).
