Gemcitabine/carboplatin (GC) vs. carboplatin (C) in platinum sensitive recurrent ovarian cancer (OVCA). Results of a Gynecologic Cancer Intergroup randomized phase III trial of the AGO OVAR, the NCIC CTG and the EORTC GCG

Abstract

5005 Background: Most patients (pts) with OVCA relapse. ICON 4 - AGO OVAR 2.2 results suggest combination C-based therapy may be superior to single agent C. GC is a feasible less neurotoxic regimen and thus of interest to evaluate in this setting. Methods: In this phase III trial pts with platinum sensitive recurrent OVCA (≥ 6 months after the end of primary therapy) were randomized to receive C (AUC 4 d1) plus G (1000 mg/m2 d1 and 8) or C (AUC 5 d1) every 3 weeks. The primary objective compared progression free survival (PFS) in both arms. Secondary objectives were response rate (RR) and duration, overall survival (OS), toxicity and quality of life (QoL). Results: From 09/99 and 04/02, 356 pts (178 GC, 178 C) were randomized. Both study arms were well balanced for baseline disease characteristics. Median number of cycles was 6 for GC (0–10) and C (0–9). The weekly dose intensity was 98.2% for C (C arm) and 96.2% for C and 75.6% (92.8% for d 1 and 63.4% for d8) for G (GC arm). Grade 3/4 hematologic toxicities were significant higher in the GC arm (anemia 27.4% of pts. vs. 8.0%, neutropenia 70.3% vs. 12.0%, thrombocytopenia 34.9% vs. 11.4%). G-CSF or GM-CSF was more often used in GC (23.6% of pts. vs. 10.1%) as well as red cell transfusions (37.1% vs. 14.6%). Clinical sequelae were similar between arms: febrile neutropenia (1.1% GC vs. 0% C) and infections (0.6% for both arms). Grade 3/4 non-hematologic toxicities were infrequent in both arms (< 5%), especially for sensory neuropathy (1.1% GC vs. 1.7% C). Overall RR for GC was 47.2% (95% CI: 39.9–54.5%) and 30.9% (95% CI: 24.1–37.7) for C (p= 0.0016). GC pts reported significantly faster palliation of abdominal symptoms as well as significantly improved global QoL. With a median follow up of 13 months, median PFS was 8.6 mo (95%CI: 8.0–9.7) for GC and 5.8 mo (95% CI: 5.2–7.1) for C (HR 0.72 [95% CI: 0.57–0.90], p= 0.0038, e= 311). OS data are immature and this study was not powered to detect differences in OS. Conclusion: The combination of G plus C improves PFS and QoL in platinum sensitive recurrent OVCA patients with acceptable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Eli Lilly Bristol-Myers Squibb; Eli Lilly Eli Lilly