Five-year KEYNOTE-045 update confirms pembrolizumab benefit in advanced UC
medwireNews: Updated results from the phase 3 KEYNOTE-045 trial show that pembrolizumab monotherapy continues to be associated with improved long-term outcomes relative to chemotherapy in advanced urothelial cancer (UC) patients who have progressed on platinum-based chemotherapy.
The overall survival (OS), objective response rate (ORR), and duration of response (DOR) were all better with the PD-1 inhibitor than investigator’s choice of chemotherapy after at least 5 years of follow-up, said Joaquim Bellmunt (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) and co-investigators in a poster at the 2021 ASCO Annual Meeting.
They continued: “These data are consistent with the primary analysis and with the 2- and 3-year follow-up analyses that led to the approval of pembrolizumab for treatment of advanced platinum-resistant or platinum-refractory UC irrespective of PD-L1 status.”
At a median time from randomization to data cutoff of 62.9 months, median OS was 10.1 months for the 270 participants who were randomly assigned to receive pembrolizumab 200 mg every 3 weeks for up to 2 years, compared with 7.2 months for their 272 counterparts who instead received physician’s choice of paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2 every 3 weeks. This equated to a significant hazard ratio (HR) of 0.71 in favor of pembrolizumab.
The OS rate at 48 months was 16.7% in the pembrolizumab arm and 10.1% in the chemotherapy arm, while the corresponding 60-month rates were 14.9% and 8.7%.
Bellmunt and colleagues highlighted that the OS advantage offered by pembrolizumab was observed regardless of factors such as age, ECOG performance status, prior therapy, liver metastases, baseline hemoglobin levels, time from last chemotherapy, histology, and chemotherapy choice.
The ORR was higher among pembrolizumab- than chemotherapy-treated patients, at 21.9% and 11.0%, respectively, with complete responses in a respective 10.0% and 2.9% and partial responses in 11.9% and 8.1%. The median DOR was also longer in the pembrolizumab than the chemotherapy group, at 29.7 versus 4.4 months.
Of note, OS was significantly improved with pembrolizumab versus chemotherapy among patients with a complete or partial response to treatment, with the median unreached and 16.4 months, respectively (HR=0.20). But there was no such difference in median OS with pembrolizumab versus chemotherapy among patients with stable (16.4 vs 10.5 months) or progressive (6.2 vs 4.7 months) disease.
The researchers said that the safety profile of pembrolizumab “was consistent with that of previous reports,” and there was a lower incidence of treatment-related adverse events of any grade (62.0 vs 90.6%) or of at least grade 3 (16.9 vs 50.2%) in the pembrolizumab versus chemotherapy group.
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany