A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

Objective: Paclitaxel and carboplatin (PC) is really a standard initial therapy for advanced endometrial cancer. We evaluated the effectiveness and tolerability of incorporating three novel agents into initial therapy.

Methods: Within this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (without or with measurable disease) endometrial cancer were at random allotted to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The main endpoint was progression-free survival (PFS). Comparable patients using the pc Arm of trial GOG209 were utilised as historic controls. Secondary endpoints were response rate, overall survival (OS), and safety.

Results: Overall, 349 patients were randomized. PFS duration wasn’t considerably elevated in almost any experimental arm in contrast to historic controls (p > .039). Treatment HRs (92% CI) for Arms 1, 2, and three in accordance with controls were .81 (.63-1.02), 1.22 (.96-1.55) and .87 (.68-1.11), correspondingly. Response rates were similar across arms (60%, 55% and 53%, correspondingly). In accordance with controls, OS duration (with censoring at 36 several weeks), was considerably elevated in Arm 1 (p < 0.039) but not in Arms 2 and 3 the HRs (92% CIs) were 0.71 (0.55-0.91), 0.99 (0.78-1.26), and 0.97 (0.77-1.23), respectively. No new safety signals were identified. Common mutations and rates of mismatch repair protein loss are described by histotype. Potential predictive biomarkers for temsirolimus and bevacizumab were identified.

Conclusion: PFS was not significantly increased in any experimental arm compared to Ixabepilone historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.