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Pembrolizumab improves OS in patients with advanced urothelial cancer
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Patients with urothelial cancer previously treated with platinum-based chemotherapy had longer OS and fewer side effects when treated with pembrolizumab compared with chemotherapy, according to data from the KEYNOTE-045 clinical trial presented at the European Cancer Congress.
Pembrolizumab (Keytruda, Merck) is an anti–PD-1 therapy currently approved for the treatment of melanoma, head and neck cancer, and lung cancer.
“KEYNOTE-045 is a landmark study. It represents a real advance in the second-line treatment of advanced bladder cancer because pembrolizumab is the first therapy to show a significant survival advantage over chemotherapy for these patients,” Andrea Necchi, MD, attending physician in the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, said in a press release.
In this phase 3 clinical trial, Necchi and colleagues randomly assigned 542 patients from 29 countries to receive 200 mg IV pembrolizumab (n = 270) or one of three investigator’s choice of chemotherapy: paclitaxel (175 mg/m2), docetaxel (75 mg/m2) or vinflunine (320 mg/m2) every 3 weeks (n = 272).
Although these three chemotherapy options have been commonly used for urothelial cancer, results have yielded little clinical benefit, Necchi and colleagues wrote.
In total, 87.3% of patients had visceral disease, 34.3% had liver metastases, 81.5% had hemoglobin greater than 10 g/dL and 38.2% had undergone their last chemotherapy treatment less than 3 months prior to starting on the current trial.
As of Sept. 7, 2016, (median follow-up, 9 months), 49 patients remained on pembrolizumab and three on chemotherapy.
Patients treated with pembrolizumab demonstrated significantly improved OS compared with patients treated with chemotherapy (median OS, 10.3 months vs. 7.4 months; HR = 0.73; 95% CI, 0.59-0.91).
The ORR also was improved in patients who received pembrolizumab compared with patients who received chemotherapy (21.1% vs. 11.4%).
However, there was no difference in PFS between the groups (median, 2.1 vs. 3.3; HR = 0.98; 95% CI, 0.81-1.19).
Median duration of response for patients treated with pembrolizumab had not been reached. Patients who responded to chemotherapy had a median duration of response of 4.3 months, Necchi said in the press release.
“We estimate that almost twice as many pembrolizumab responders will respond to therapy for at least one year: 68% vs. 35%,” Necchi added.
Fewer patients treated with pembrolizumab experienced side effects of any grade compared with patients treated with chemotherapy (60.9% vs. 90.2%).
More grade 3 to grade 5 adverse events were observed in patients treated with chemotherapy compared with patients treated with pembrolizumab (49.4% vs. 15%). Four patients in each arm died of treatment-related adverse events.
“This is important because this patient population tends to be mostly elderly patients who have many other illnesses and health conditions as well,” Necchi said. “These results support the use of pembrolizumab as the new standard of care for advanced bladder cancer.” – by Melinda Stevens
Reference:
Necchi A, et al. Abstract 3LBA. Presented at: European Cancer Congress; January 27-30; Amsterdam.
Disclosures: The study was funded by Merck. Necchi reports advisory board roles with and corporate-sponsored research funding from AstraZeneca, Bayer Merck, Millennium/Takeda, Novartis and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.