KEY TAKEAWAYS
- Phase II KEYNOTE-158 trial aims to assess the efficacy of pembrolizumab monotherapy to treat cancer patients with no prior treatments, failure, or intolerance to previous treatments based on the (RECIST) v1.1 assessment.
- The trial’s primary outcome measure was ORR based on an independent central radiologic review, while DoR, PFS, OS, and AEs were the secondary outcome measures.
- Pembrolizumab monotherapy proved clinically meaningful regardless of tumor PD-L1 expression.
The multicohort phase 2 KEYNOTE-158 trial assessed pembrolizumab monotherapy in patients with previously treated cancers. According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, eligible patients had the measurable disease as well as previous therapy failure or intolerance. The main outcome was the objective response rate (ORR) according to RECIST v1.1 by impartial central review.
For up to 35 cycles, patients got 200 mg of pembrolizumab (pembrolizumab) every 3 weeks. Pembrolizumab was administered to 103 individuals in total. The median time from the first dosage to the data cutoff (October 5, 2020) was 49.4 months (with a range of 43.9 to 54.9). The ORR was 6.8% (95% CI, 2.8%-13.5%), and the median reaction time was 18.4 (range, 4.2-47.2+) months.
Programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 patient had an ORR of 8.7% (95% CI, 2.4%-20.8%), while PD-L1 CPS <1 patient had an ORR of 5.7% (95% CI, 1.2%-15.7%). The median overall survival was 34.5 months (95% CI: 21.2 to not reached), and the median progression-free survival was 4.2 months (95% CI: 3.9-6.2). 69.9% of patients experienced treatment-related side effects (rating 3-5, 14.6%).
Pembrolizumab showed tolerable toxicity and long-lasting antitumor activity in a small subset of patients. The findings showed some antitumor action, despite tumor PD-L1 expression. Future studies should concentrate on biomarker-driven patient selection or combining immune checkpoint inhibitors with other drugs to achieve higher response rates than those seen in the research.
Source: https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34657
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02628067
Oh, D. Y., Algazi, A., Capdevila, J., Longo, F., Miller, W., Jr, Chun Bing, J. T., Bonilla, C. E., Chung, H. C., Guren, T. K., Lin, C. C., Motola-Kuba, D., Shah, M., Hadoux, J., Yao, L., Jin, F., Norwood, K., & Lebellec, L. (2023). Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Cancer, 10.1002/cncr.34657. Advance online publication. https://doi.org/10.1002/cncr.34657
