(CHICAGO, IL)—Topotecan plus carboplatin failed to improve progression-free survival (PFS) or overall survival (OS) compared with standard therapy (paclitaxel/carboplatin, gemcitabine/carboplatin, or carboplatin/pegylated doxorubicin) in patients with platinum-sensitive relapsed ovarian cancer, according to results of the randomized phase 3 HECTOR study presented at the 2012 American Society of Clinical Oncology Annual Meeting.
The NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG intergroup study found the carboplatin plus gemcitabine regimen to be well tolerated, with lower rates of severe and long-lasting toxicities (eg, neuropathy) compared with paclitaxel plus carboplatin, said lead author Prof. Dr. med. Jalid Sehouli, of the European Competence Center for Ovarian Cancer, Charité Campus Virchow Klinikum, Berlin, Germany.
A total of 590 patients with epithelial ovarian carcinoma, peritoneal or tubal carcinoma, and disease relapse/progression ≥6 months after the end of platinum-containing primary or secondary therapy were enrolled between February 2007 and December 2009; 550 were randomized to receive topotecan 0.75mg/m² on Days 1 –3 every 21 days plus carboplatin AUC 5 on Day 3 every 21 days or to standard therapy with paclitaxel/carboplatin, gemcitabine/carboplatin, or carboplatin/pegylated doxorubicin based on patient preference. The primary end point was PFS at 1 year.
Median number of cycles was 6 (range, 0-9) in all treatment arms.
At 1 year, PFS was 37.0% in the topotecan/carboplatin arm (n=270), 49.3% in the paclitaxel/carboplatin arm (n=79) and 36.8% in the gemcitabine/carboplatin arm (n=189; P=0.215). A total of 5 patients were treated in the carboplatin/pegylated doxorubicin arm.
Median PFS was 10 months in the topotecan/carboplatin arm, 12 months in the paclitaxel/carboplatin arm, and 10 months in the gemcitabine/carboplatin arm (P=0.472). Median OS was 25 months in the topotecan/carboplatin arm, 29 months in the paclitaxel/carboplatin arm, and 33 months in the gemcitabine/carboplatin arm (P=0.340)
Best response (complete response plus partial response) was 73.1% for the topotecan/carboplatin group and 75.1% for the standard therapy arm. Median follow-up was 18 months (range, 0-52) months for topotecan/carboplatin and 20 months (range, 0-48) for standard therapy.
Most aspects of quality of life worsened during chemotherapy for all treatment groups in a similar manner, Dr. Sehouli reported, but peripheral neuropathy and other side effects of chemotherapy increased more in the carboplatin/paclitaxel group than in the topotecan/carboplatin or gemcitabine/carboplatin groups (P<0.001). In fact, most patients (67%) preferred standard therapy with gemcitabine/carboplatin, Dr. Sehouli said.
Grade 3 or 4 neutropenia was 27.8% in the topotecan/carboplatin arm, 34.2% in the paclitaxel/carboplatin arm, and 40.7% in the gemcitabine/carboplatin arm (P=0.015) and grade 3 or 4 thrombocytopenia was 15.2%, 3.8%, and 41.8%, respectively (P<0.001). Neuropathy grade 2 or higher was 10.8%, 17.7%, and 8.5% (P=0.073), respectively. No grade 2 or higher hand-foot syndrome was observed in the topotecan/carboplatin, paclitaxel/carboplatin, or gemcitabine/carboplatin arms.
Early treatment discontinuation that was toxicity related (<6 cycles) was 15.9% in the topotecan/carboplatin arm, 7.6% in the paclitaxel/carboplatin arm, and 13.2% in the gemcitabine/carboplatin arm (P=0.162), he noted.