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PFS correlated with OS in urothelial cancer
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PFS at 6 and 9 months predicted OS in a cohort of patients with metastatic urothelial carcinoma who were treated with first-line cisplatin-based chemotherapy, according to study results.
Matthew D. Galsky, MD, director of genitourinary medical oncology at Mount Sinai School of Medicine’s Tisch Cancer Institute, and colleagues suggested that 6- and 9-month PFS could serve as endpoints in randomized phase 2 trials designed to screen the activity of novel regimens.
Matthew D. Galsky
Up to 60% of patients with metastatic urothelial carcinoma achieve objective response to cisplatin-based combination chemotherapy, and 10% to 20% achieve complete response. However, response durations often are short-lived, and median OS is only about 14 months. No advances in the efficacy of therapy have been made in the past 3 decades, according to background information provided by researchers.
“Tumor response rate has not convincingly proven useful in selecting phase 2 regimens worthy of moving forward to definitive randomized trials in this clinical disease state, likely contributing to the lack of progress in drug development,” Galsky and colleagues wrote. “PFS offers the potential to encompass an aspect of ‘disease control’ not captured by focusing on tumor shrinkage alone.”
The current analysis included data from seven phase 2 and 3 trials that evaluated cisplatin-based chemotherapy in patients with metastatic urothelial cancer treated with first-line cisplatin-based chemotherapy.
Results were externally validated using an independent cohort of patients in a phase 3 trial. In addition, attempts were made to minimize lead time bias by conducting landmark analyses at 6 and 9 months after treatment began.
The initial cohort included 364 patients. Overall, researchers reported a median PFS of 8.21 months (95% CI, 7.43-8.39) and a median OS of 13.5 months (95% CI, 11.80-15.67).
At 6 months, median OS was 3.87 among patients who had progressed and 15.06 months for patients who had not progressed (P<.0001), according to landmark analysis results.
At 9 months, the median OS was 5.65 months for patients who had progressed and 21.39 months for those who did not progress (P<.0001).
A statistically significant dependent correlation between the two survival endpoints existed, according to Fleisher model results. The independent cohort analysis validated this result.
“Six- and 9-month PFS is highly correlated with OS in metastatic urothelial cancer,” Galsky and colleagues concluded. “This study provides benchmarks for 6- and 9-month PFS endpoints for future clinical trial design. Phase 2 randomized trials using 6- or 9-month PFS as a primary endpoint may overcome many of the limitations of current phase 2 clinical trial design in patients with chemotherapy-naïve metastatic urothelial cancer and better inform ‘go/no-go’ decisions in this clinical disease state moving forward.”
Disclosure: The researchers report research support from Bristol-Myers Squibb, Celgene, Exelixis, Genentech, Merck, Millennium, Novartis, Pfizer and Sanofi; honoraria from and speaker’s bureau roles with Janssen and Medivation; and consultant roles with Celgene and GlaxoSmithKline.
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