KEY TAKEAWAYS
- The study is a Phase 3 trial named KEYNOTE-052 aimed to compare the overall survival and progression-free survival of patients with metastatic urothelial carcinoma.
- Patients were randomly assigned to receive pembrolizumab or chemotherapy as determined by the investigator.
- Pembrolizumab demonstrated higher overall survival and progression-free survival rates than chemotherapy in KEYNOTE-045.
- Most adverse events associated with pembrolizumab were of grade 1 or 2 severity and controllable.
- Pembrolizumab demonstrated durable efficacy in patients with metastatic urothelial carcinoma who were resistant to platinum-based therapy.
Utilizing immune checkpoint inhibitors is a traditional therapeutic approach that managed urothelial carcinoma (UC). Sustained monitoring was imperative to validate the endurance of the reaction and detect any additional safety issues. The clinical trial KEYNOTE-045 involved patients diagnosed with metastatic urothelial carcinoma who had experienced progression after undergoing chemotherapy containing platinum. These patients were randomly assigned to receive either pembrolizumab or a selection of paclitaxel, docetaxel, or vinflunine, as determined by the investigator. The study’s primary endpoints were progression-free survival per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evaluated by a blinded independent central review (BICR), and overall survival.
The study KEYNOTE-052 administered first-line pembrolizumab to patients with metastatic urothelial carcinoma who were ineligible for cisplatin. The study’s primary endpoint was the objective response rate per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, assessed by a blinded independent central review. In the KEYNOTE-045 study, 542 patients were randomly assigned, with 270 receiving pembrolizumab and 272 receiving chemotherapy.
The study’s median follow-up duration was 62.9 months, with a range of 58.6-70.9 months and a data cut-off date of 1 October 2020. At 48 months, the pembrolizumab treatment exhibited an overall survival rate of 16.7%, while the chemotherapy treatment showed a rate of 10.1%. Regarding progression-free survival, pembrolizumab exhibited a rate of 9.5%, while chemotherapy exhibited a rate of 2.7%. The study reports that the median duration of response (DOR) for pembrolizumab was 29.7 months (range 1.6+ to 60.5+ months), while for chemotherapy, it was 4.4 months (range 1.4+ to 63.1+ months). The 36-month DOR rates for pembrolizumab and chemotherapy were 44.4% and 28.3%, respectively. The clinical trial KEYNOTE-052 included a total of 370 patients. The study’s median follow-up duration was 56.3 months, with a range of 51.2-65.3 months and a data cut-off date of 26 September 2020. The study reported a confirmed objective response rate of 28.9% with a 95% confidence interval of 24.3-33.8. The median duration of response (DOR) was 33.4 months, ranging from 1.4+ to 60.7+ months. The 36-month DOR rate was found to be 44.8%. Most treatment-associated unfortunate occurrences for pembrolizumab in both investigations were of grade 1 or 2 severity and were controllable by previous findings.
After approximately five years of follow-up, the efficacy of pembrolizumab monotherapy remained durable, and no new safety signals were observed in patients with metastatic urothelial carcinoma who were resistant to platinum-based therapy. Additionally, pembrolizumab demonstrated efficacy as a first-line therapy in patients ineligible for cisplatin-based treatment.
Source:https://pubmed.ncbi.nlm.nih.gov/36494006/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02335424
Balar AV, Castellano DE, Grivas P, Vaughn DJ, Powles T, Vuky J, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Necchi A, Petrylak DP, Plimack ER, Xu JZ, Imai K, Moreno BH, Bellmunt J, de Wit R, O’Donnell PH. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Ann Oncol. 2023 Mar;34(3):289-299. doi: 10.1016/j.annonc.2022.11.012. Epub 2022 Dec 6. PMID: 36494006.
