KEY TAKEAWAYS
- KEYNOTE-045 and KEYNOTE-052 are clinical trials investigating pembrolizuma as standard therapy for metastatic UC in patients who progressed on platinum-containing chemotherapy or were ineligible for cisplatin.
- The primary endpoints of these trials were progression-free survival and overall survival rates, as well as objective response rates per RECIST version 1.1 by BICR.
- With a median follow-up of approximately 5 years, pembrolizumab monotherapy demonstrated durable efficacy in both trials, with OS rates at 48 months of 16.7% for KEYNOTE-045 and a confirmed objective response rate of 28.9% for KEYNOTE-052.
- The median duration of response was 29.7 months for KEYNOTE-045 and 33.4 months for KEYNOTE-052, with 36-month DOR rates of 44.4% and 44.8%, respectively.
- Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, with no new safety signals identified.
Metastatic urothelial carcinoma (UC) is typically treated with immune checkpoint medications. First, however, the response’s longevity must be confirmed over the long term, and any further safety problems must be uncovered through careful monitoring.
Pembrolizumab, or the investigator’s choice of paclitaxel, docetaxel, or vinflunine was randomly assigned to patients with metastatic UC who had progressed on platinum-containing chemotherapy in the KEYNOTE-045 trial. Progression-free survival as measured by RECIST 1.1 and overall survival as determined by blinded independent central review (BICR) served as the primary objectives. Patients with metastatic UC who were ineligible for cisplatin were given pembrolizumab as first-line treatment in KEYNOTE-052. To measure efficacy, BICR used an objective response rate based on RECIST 1.1.
The KEYNOTE-045 study randomized 542 individuals (272 to receive chemotherapy and 270 to receive pembrolizumab). The average duration of follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, the overall survival rate for those who received pembrolizumab was 16.7%, whereas the rate for those who received chemotherapy was 10.1%. In addition, Pembrolizumab patients had a median DOR of 29.7 months (range, 1.6+ to 60.5+ months), whereas chemotherapy patients had a median DOR of 4.4 months (range, 1.4+ to 63.1+ months); the corresponding 36-month DOR rates were 44.4% and 28.3%. Overall, 370 participants joined KEYNOTE-052.
The average duration of follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The median duration of response (DOR) was 33.4 months (range 1.4+ to 60.7+ months), and the 36-month DOR rate was 44.8%. The verified objective response rate was 28.9% (95% confidence interval 24.3-33.8). Consistent with previous findings, most treatment-related side events with pembrolizumab in either study were mild and easily treatable. Pembrolizumab monotherapy in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients has shown sustained efficacy with >5 years of follow-up and no new safety flags.
Source: https://pubmed.ncbi.nlm.nih.gov/36494006/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02256436
Balar, A.V., Castellano, D.E., Grivas, P., Vaughn, D.J., Powles, T., Vuky, J., Fradet, Y., Lee, J.-L. ., Fong, L., Vogelzang, N.J., Climent, M.A., Necchi, A., Petrylak, D.P., Plimack, E.R., Xu, J.Z., Imai, K., Moreno, B.H., Bellmunt, J., de Wit, R. and O’Donnell, P.H. (2023). Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Annals of Oncology, 34(3), pp.289–299. doi:https://doi.org/10.1016/j.annonc.2022.11.012.
