The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.
Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.
The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.
“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”
The results have now beenin the Journal of Clinical Oncology.
The Gynecologic Oncology Group 177 trial established TAP aboutas the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.
Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that
Equivalent survival, lower toxicity
In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reportedand health-related quality of life (HRQoL).
From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. 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.
After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.
In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.
Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.
As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%),(6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of was greater with TC (52% vs. 80%).
Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.
On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.
Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.
The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.
A version of this article originally appeared on.