Adding pembrolizumab to first-line chemotherapy did not significantly prolong progression-free survival (PFS) or overall survival (OS) in patients with advanced urothelial carcinoma, according to a study published in The Lancet Oncology.
The phase 3 KEYNOTE-361 trial (ClinicalTrials.gov, number NCT02853305) enrolled 1010 patients with previously untreated advanced urothelial carcinoma.
The patients were randomly assigned to receive pembrolizumab monotherapy (n=307), pembrolizumab plus chemotherapy (n=351), or chemotherapy alone (n=352). The patients were stratified by choice of platinum therapy and PD-L1 combined positive score (CPS).
At the final analysis, the median follow-up was 31.7 months. The primary endpoints were PFS and OS. The P value boundary was .0019 for PFS and .0142 for OS.
There was no significant difference in median PFS between the pembrolizumab-chemotherapy arm and the chemotherapy-alone arm — 8.3 months and 7.1 months, respectively (hazard ratio [HR], 0.78; 95% CI, 0.65-0.93; P =.0033).
Likewise, there was no significant difference in median OS between the pembrolizumab-chemotherapy arm and the chemotherapy-alone arm — 17.0 months and 14.3 months, respectively (HR, 0.86; 95% CI, 0.72-1.02; P =.0407).
The median OS was also similar for the pembrolizumab-alone arm and the chemotherapy-alone arm. This was true in the overall population — 15.6 months and 14.3 months, respectively (HR, 0.92, 95% CI, 0.77-1.11) — and in patients with a PD-L1 CPS of at least 10 — 16.1 months and 15.2 months, respectively (HR, 1.01; 95% CI, 0.77-1.32).
The most common serious treatment-related adverse event (TRAE) was anemia in both the pembrolizumab-chemotherapy arm (3%) and the chemotherapy-alone arm (4%). The most common serious TRAE in the pembrolizumab-alone arm was pneumonitis (1%).
There were 6 patients who died from TRAEs. In the pembrolizumab-chemotherapy arm, 1 patient died from cardiac arrest and 1 from device-related sepsis.
In the pembrolizumab-alone arm, 1 patient died from cardiac failure and 1 from malignant neoplasm progression. In the chemotherapy-alone arm, 1 patient died from myocardial infarction and 1 from ischemic colitis.
“This trial adds to the growing body of evidence showing that immune checkpoint inhibitors given with chemotherapy are not associated with clear survival benefits for
urothelial carcinoma,” the study authors wrote.
“Based on the primary findings of the KEYNOTE-361 study, platinum-based chemotherapy remains the current first-line standard of care for patients able to receive it, with avelumab maintenance therapy for those who have a clinical benefit.”
Disclosures: This research was supported by Merck Sharp and Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Powles T, Csőszi T, Özgüroğlu M, et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): A randomised, open-label, phase 3 trial. Lancet Oncol. Published Online May 26, 2021. doi: 10.1016/S1470-2045(21)00152-2