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

Abstract

Purpose: 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.

Methods: 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.

Results: From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 v 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 v 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 (P = .40). More grade ≥ 3 thrombocytopenia (23% v 12%), vomiting (7% v 4%), diarrhea (6% v 2%), and metabolic (14% v 8%) toxicities were reported with TAP. Neutropenia (52% v 80%) was more common with TC. Small HRQoL differences favored TC.

Conclusion: With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.

Trial registration: ClinicalTrials.gov NCT00063999.

Figures

FIG 1.

CONSORT diagram. AE, adverse event; AUC, area under the curve; IV, intravenous; LVEF, left ventricular ejection fraction; TAP, paclitaxel-doxorubicin-cisplatin.

FIG 2.

Updated progression-free survival time distribution by randomized treatment group. Carbo, carboplatin; pac, paclitaxel; TAP, paclitaxel-doxorubicin-cisplatin.

FIG 3.

Updated overall survival time distribution by randomized treatment group. Carbo, carboplatin; pac, paclitaxel; TAP, paclitaxel-doxorubicin-cisplatin.

FIG 4.

Overall survival treatment hazard ratio (HR) forest plots by subgroup. All estimates are based on a model stratified by disease group and performance status. The reference group is paclitaxel-doxorubicin-cisplatin (TAP). ER, estrogen receptor; HR, hazard ratio: IDA, initial dose adjustment; LCL, lower confidence limit; NM, nonmeasurable; PR, progesterone receptor; RT, radiotherapy; UCL, upper confidence limit.

FIG 5.

Updated survival time distribution by treatment group and measurable disease status. All estimates are based on a model stratified by disease group and performance status. Carbo, carboplatin; meas, measurable; pac, paclitaxel; rec, recurrent; TAP, paclitaxel-doxorubicin-cisplatin.

FIG A1.

Observed Physical Well-Being (PWB) subscore plus Functional Well-Being (FWB) score by randomized treatment group. PAC, paclitaxel-doxorubicin-cisplatin.