KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy of adding berzosertib to gemcitabine and cisplatin in patients with mUC.
- The primary endpoint was to determine PFS.
- Researchers noticed no PFS or OS benefit by adding berzosertib to gemcitabine and cisplatin in mUC patients.
Gemcitabine with cisplatin (GC) remains a frontline treatment option for patients with metastatic urothelial cancer (mUC). Preclinical synergy has been noted when combining cisplatin with berzosertib, a selective ATR inhibitor.
Mamta Parikh and the team aimed to determine the effect of adding berzosertib to GC on clinical outcomes in mUC; here, they presented the final study results with extended follow-up.
Researchers performed an inclusive analysis in this open-label, randomized study, enrolling patients with confirmed mUC who had not received prior cytotoxic therapy for metastatic disease and had undergone perioperative chemotherapy over 12 months prior, meeting eligibility criteria for cisplatin. Patients were randomized into two arms: Arm A received GC plus berzosertib, while Arm B received GC alone.
In Arm A, cisplatin 60 mg/m2 IV was administered on Day 1 (D1), gemcitabine 875 mg/m2 IV on D1 & 8, and berzosertib 90 mg/m2 IV on D2 & 9 of a 21-day cycle. In Arm B, cisplatin 70 mg/m2 IV was given on D1 and gemcitabine 1000 mg/m2 IV on D1 & 8 of a 21-day cycle. The primary endpoint was progression-free survival (PFS), with secondary endpoints including response rate (RR), overall survival (OS), and toxicity.
About 87 patients (median age 67; M:F 68:19) were randomized, with 46 patients in Arm A and 41 in Arm B. With a median follow-up of 37.7 months (95% CI: 28.3, 39.3), median PFS was 6.2 months in Arm A and 7.1 months in Arm B (HR: 1.3 [95% CI: 0.8-2.2], P=0.1). The response rate (RR) was 54% in Arm A and 63% in Arm B. Median OS was 10.9 months in Arm A and 19.8 months in Arm B (HR: 1.2 [95% CI: 0.7-2.1], P=0.2).
The common adverse events > Grade 3 included anemia (Arm A: 57%, Arm B: 24%), neutropenia (Arm A: 36.9%, Arm B: 26.8%), and thrombocytopenia (Arm A: 58.7%, Arm B: 39%).
The study concluded that there was no PFS or OS benefit observed with the addition of berzosertib to gemcitabine and cisplatin compared to gemcitabine and cisplatin alone in a biomarker unselected population, even with over 18 months of extended follow-up. Myelosuppression remained common despite reduced dosing of cisplatin and gemcitabine, indicating challenges in combining ATR inhibition with platinum-based chemotherapy in patients with mUC.
The study was sponsored by National Cancer Institute (NCI)
Source: https://meetings.asco.org/abstracts-presentations/229769
Clinical Trial: https://clinicaltrials.gov/study/NCT02567409
Parikh M, Pal S K, Frankel P H, et al. (2024). “Extended follow-up report of a randomized phase II trial comparing gemcitabine and cisplatin with or without berzosertib in patients with advanced urothelial carcinoma.” Presented At ASCO-GU 2024, Abstract (614).
