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

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. In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disea...

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Vydáno v:Gynecologic oncology Ročník 150; číslo 2; s. 274 - 281
Hlavní autoři: Aghajanian, Carol, Filiaci, Virginia, Dizon, Don S., Carlson, Jay W., Powell, Matthew A., Secord, Angeles Alvarez, Tewari, Krishnansu S., Bender, David P., O'Malley, David M., Stuckey, Ashley, Gao, JianJiong, Dao, Fanny, Soslow, Robert A., Lankes, Heather A., Moore, Kathleen, Levine, Douglas A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 01.08.2018
Témata:
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bevacizumab
Bevacizumab - administration & dosage
Carboplatin
Carboplatin - administration & dosage
Endometrial cancer
Endometrial Neoplasms - drug therapy
Epothilones - administration & dosage
Female
Hematology, Oncology, and Palliative Medicine
Humans
Ixabepilone
Middle Aged
Neoplasm Recurrence, Local - drug therapy
Obstetrics and Gynecology
Paclitaxel
Paclitaxel - administration & dosage
Sirolimus - administration & dosage
Sirolimus - analogs & derivatives
Temsirolimus
Carboplatin
Temsirolimus
Ixabepilone
Endometrial cancer
Paclitaxel
Bevacizumab
ISSN:0090-8258, 1095-6859, 1095-6859
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Popis
Shrnutí: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. 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. 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. PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P. •Paclitaxel + carboplatin is standard initial therapy for advanced endometrial cancer.•We assessed combinations with bevacizumab, temsirolimus or ixabepilone.•PFS was not significantly improved compared to historical control.
Bibliografie:ObjectType-Article-2
SourceType-Scholarly Journals-1
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Study concept and design: Aghajanian C, Filiaci V, Dizon DS, Levine DA
Final approval of manuscript: Aghajanian C, Filiaci V, Dizon DS, Carlson JW, Powell MA, Alvarez Secord A, Tewari KS, Bender DP, O’Malley DM, Stuckey A, Gao J, Dao F, Soslow RA, Lankes HA, Moore K, Levine DA
Analysis and interpretation of data: Aghajanian C, Filiaci V, Gao J, Dao F, Soslow RA, Lankes HA, Levine DA
Manuscript writing: Aghajanian C, Filiaci V, Gao J, Dao F, Lankes HA, Levine DA
Critical review of the manuscript: Filiaci V, Dizon DS, Carlson JW, Powell MA, Alvarez Secord A, Tewari KS, Bender DP, O’Malley DM, Stuckey A, Soslow RA, Moore K, Levine DA
Acquisition of data: Aghajanian C, Dizon DS, Carlson JW, Powell MA, Alvarez Secord A, Tewari KS, Bender DP, O’Malley DM, Stuckey A, Gao J, Dao F, Soslow RA, Lankes HA, Moore K, Levine DA
AUTHOR CONTRIBUTIONS
Provision of materials or patients: Aghajanian C, Dizon DS, Carlson JW, Powell MA, Alvarez Secord A, Tewari KS, Bender DP, O’Malley DM, Stuckey A, Moore K
ISSN:0090-8258
1095-6859
1095-6859
DOI:10.1016/j.ygyno.2018.05.018