Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209).

Abstract

Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic Oncology Group studied carboplatin plus paclitaxel (TC) as a noninferior alternative to TAP. GOG0209 was a phase III, randomized, noninferiority, open-label trial. Inclusion criteria were stage III, stage IV, and recurrent endometrial cancers; performance status 0-2; and adequate renal, hepatic, and marrow function. Prior radiotherapy and/or hormonal therapy were permitted, but chemotherapy, including radiosensitization, was not. Patients were treated with doxorubicin 45 mg/m² and cisplatin 50 mg/m² (day 1), followed by paclitaxel 160 mg/m² (day 2) with granulocyte colony-stimulating factor or paclitaxel 175 mg/m² and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles. The primary endpoint was overall survival (OS; modified intention to treat). Progression-free survival (PFS), health-related quality of life (HRQoL), and toxicity were secondary endpoints. From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 <i>v</i> 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 <i>v</i> 14 months; HR, 1.032; 90% CI, 0.93 to 1.15). Neutropenic fever was reported in 7% of patients receiving TAP and 6% of those receiving TC. Grade > 2 sensory neuropathy was recorded in 26% of patients receiving TAP and 20% receiving TC (<i>P</i> = .40). More grade ≥ 3 thrombocytopenia (23% <i>v</i> 12%), vomiting (7% <i>v</i> 4%), diarrhea (6% <i>v</i> 2%), and metabolic (14% <i>v</i> 8%) toxicities were reported with TAP. Neutropenia (52% <i>v</i> 80%) was more common with TC. Small HRQoL differences favored TC. With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.