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.

A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial

“…Fleming et al, reported that the RR of PTX, cisplatin, and doxorubicin (TAP) regimens was 57% [ 8 9 ]. Similarly, Miller et al, [ 10 ] reported the RR of both PTX plus CBDCA (TC) and TAP to be approximately 50%. The RR of our trial treatment using one of the conventional TCs was expected to increase by 20%.…”

“…Supposedly, the reason for these findings was that Katsumata et al, [ 12 13 ] and other researchers set the dosage of CBDCA to an AUC of 6 mg∙h/L. However, the number of patients was higher in the dd regimen group than in the conventional regimen group (n=113 vs. n=69) [ 9 10 ]. The ICON8 trial was set at an AUC of 5 or 6, based on the investigators' discretion [ 14 ].…”

Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology

“…Until recently, cytotoxic chemotherapies were the gold standard for metastatic endometrial cancer treatment, whatever the line of treatment. The first-line regimen for advanced EC is still the combination of carboplatin and paclitaxel with overall response rates (ORR) of 50 to 60%, median progression-free survival of one year, and a median overall survival slightly of above three years [40,41]. After platinum failure, mono-chemotherapies are routinely used with poor results.…”

The GOG partners: A program for industry sponsored clinical trials in gynecologic oncology within the GOG foundation

“…The existing use of paclitaxel in ovarian [12], cervical [13] and endometrial [14] cancers is based on randomized phase 3 GOG-F studies. The first FDA approved agent in cervical cancer (topotecan) [15] and the first FDA approved targeted therapy in gynecologic cancer (bevacizumab in first-line metastatic cervical cancer) [16,17] are based on GOG-F studies.…”