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

Abstract

OBJECTIVE:

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

METHODS:

In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) endometrial cancer were randomly assigned to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The primary endpoint was progression-free survival (PFS). Comparable patients on the PC Arm of trial GOG209 were used as historical controls. Secondary endpoints were response rate, overall survival (OS), and safety.

RESULTS:

Overall, 349 patients were randomized. PFS duration was not significantly increased in any experimental arm compared with historical controls (p > 0.039). Treatment HRs (92% CI) for Arms 1, 2, and 3 relative to controls were 0.81 (0.63-1.02), 1.22 (0.96-1.55) and 0.87 (0.68-1.11), respectively. Response rates were similar across arms (60%, 55% and 53%, respectively). Relative to controls, OS duration (with censoring at 36 months), was significantly increased 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 historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.

• Authors: Carol Aghajanian, Virginia Filiaci, Don S Dizon, Jay W Carlson, Matthew A Powell, Angeles Alvarez Secord, Krishnansu S Tewari, David P Bender, David M O'Malley, Ashley Stuckey, JianJiong Gao, Fanny Dao, Robert A Soslow, Heather A Lankes, Kathleen Moore, Douglas A Levine
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 150 Issue 2 Pg. 274-281 (08 2018) ISSN: 1095-6859 [Electronic] United States
• PMID: 29804638 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Epothilones
• Bevacizumab
• temsirolimus
• Carboplatin
• ixabepilone
• Paclitaxel
• Sirolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab (administration & dosage)
• Carboplatin (administration & dosage)
• Endometrial Neoplasms (drug therapy)
• Epothilones (administration & dosage)
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Paclitaxel (administration & dosage)
• Sirolimus (administration & dosage, analogs & derivatives)