Leslie S. Bradford

Comparing Durvalumab, Olaparib, and Cediranib Monotherapy, Combination Therapy, or Chemotherapy in Patients with Platinum-Resistant Ovarian Cancer with Prior Bevacizumab: The Phase II NRG-GY023 Trial

Abstract Purpose: We assessed the efficacy of anti–PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared with the standard-of-care chemotherapy (SOC) in patients with platinum-resistant ovarian cancer (PROC), who had prior bevacizumab. Patients and Methods: NRG-GY023 was the first randomized four-arm superiority phase II trial enrolling patients with high-grade serous/endometrioid or clear-cell PROC with prior bevacizumab exposure. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin), DOC, durvalumab + cediranib (DC), or olaparib + cediranib (OC). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, overall response rate, and safety. The design had 80% power to detect an HR of 0.5 using a one-sided, α = 0.1-level test for each comparison with the SOC with a preplanned interim analysis. Experimental arms with HR estimates (vs. SOC) >0.87 could be discontinued. Results: A total of 153 patients were enrolled between April 4, 2021, and February 1, 2023. Accrual was permanently closed on February 1, 2023, due to futility. With a data cutoff of September 9, 2024, the median PFS was 3.4, 2.9, 2.5, and 2.8 months, and median overall survival was 7.5, 8.3, 5.7, and 10.2 months for SOC, DOC, DC, and OC, respectively. The overall response rate was 4.3% [95% confidence interval (CI), 0.00–0.19], 15.9% (95% CI, 0.07–0.29), 11.9% (95% CI, 0.05–0.24), and 9.1% (95% CI, 0.03–0.20) for SOC, DOC, DC, and OC, respectively. Compared with SOC, the PFS HR estimates were 1.003 (95% CI, 0.56–1.80), 1.108 (95% CI, 0.63–1.96), and 1.021 (95% CI, 0.57–1.82) for DOC, DC, and OC, respectively. No new safety signals were observed. Conclusions: In patients with PROC with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.

Impact of geography and travel distance on outcomes in epithelial ovarian cancer: a national cancer database analysis

As ovarian cancer treatment shifts to provide more complex aspects of care at high-volume centers, almost a quarter of patients, many of whom reside in rural counties, will not have access to those centers or receive guideline-based care. To explore the association between proximity of residential zip code to a high-volume cancer center with mortality and survival for patients with ovarian cancer. The National Cancer Database was queried for cases of newly diagnosed ovarian cancer between January 2004 and December 2015. Our predictor of interest was distance traveled for treatment. Our primary outcomes were 30-day mortality, 90-day mortality, and overall survival. The effect of treatment on survival was analyzed with the Kaplan-Meier method. Multiple logistic regression for binary outcomes and Cox proportional hazards regression for overall survival were used to assess the effect of distance on outcome, controlling for potential confounding variables. A total of 115 540 patients were included. There was no statistically significant difference in 30- or 90-day mortality among any of the travel distance categories. A statistically significant decrease in 30-day re-admission was found among patients who lived further away from the treating facility. A total of 105 529 patients were available for survival analysis, and survival curves significantly differed between distance strata (p50 miles from a high-volume treatment facility. With a national policy shift toward centralization of complex care, a better understanding of the impact of distance on survival in patients with ovarian cancer is crucial. Our findings inform the practice of healthcare delivery, especially in rural settings.