KEY TAKEAWAYS
- Results of the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), evaluated pembrolizumab monotherapy in patients with previously treated cancers, including papillary or follicular thyroid carcinoma.
- Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles, and the primary endpoint was ORR per RECIST v1.1 by independent central review.
- The ORR was 6.8% (95% CI, 2.8%-13.5%), and the median duration of response was 18.4 (range, 4.2-47.2+) months. The ORR was slightly higher among patients with PD-L1 combined positive score (CPS) ≥1 (n = 46) compared to those with PD-L1 CPS <1 (n = 53).
- Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grades 3-5, 14.6%).
Thyroid carcinoma patients who participated in the phase 2 KEYNOTE-158 study (NCT02628067) are presented with data from the evaluation of pembrolizumab monotherapy in patients with previously treated malignancies. Patients were considered for enrollment if they had histologically or cytologically proven papillary or follicular thyroid cancer had progressed on or been intolerant of prior therapy, and had detectable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants were given pembrolizumab (200 mg) every 3 weeks for a maximum of 35 cycles. The primary outcome was ORR, measured by central independent review using RECIST v1.1.
Pembrolizumab was administered to 103 individuals. They found that the median time between the first dose and the end of the data set (October 5, 2020) was 49.4 months (range, 43.9-54.9 months). The median response length was 18.4 months (range, 4.2 to 47+ months), and the overall response rate was 6.8% (95% CI, 2.8%-13.5%). 8.7% (95% CI, 2.4%-20.8%) among patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) 1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with a PD-L1 CPS 1 (n = 53) in terms of overall survival. The 95% CI for the median overall survival was 21.2 to not attained, while the 95% CI for the progression-free survival was 3.9 to 6.2 months.
Patients experienced treatment-related adverse events at a rate of 69.9% (14.6 occurrences of category 3-5). In a subset of patients with advanced thyroid carcinoma, pembrolizumab showed tolerable tolerability and sustained anticancer efficacy. These findings suggest a low level of anticancer activity in this scenario, independently of PD-L1 expression in the tumor. For better response rates in future studies with immune checkpoint inhibitors in patients with differentiated thyroid cancer, biomarker-driven patient selection or combination with other treatments may be necessary.
Source: https://pubmed.ncbi.nlm.nih.gov/36748723/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02628067
Oh, D., Algazi, A., Capdevila, J., Longo, F., Miller Jr, W., Chun Bing, J.T., Bonilla, C.E., Chung, H.C., Guren, T.K., Lin, C., Motola‐Kuba, D., Shah, M., Hadoux, J., Yao, L., Jin, F., Norwood, K. and Lebellec, L. (2023). Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE‐158 study. Cancer. doi:https://doi.org/10.1002/cncr.34657.
