Combination Regimen Prolongs PFS in Recurrent Ovarian Cancer but Decreases Quality of Life

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According to a study presented at the Society of Gynecologic Oncology 41st Annual Meeting on Women’s Cancer, held in San Francisco, California, a combination of docetaxel (Taxotere) and carboplatin almost doubled progression-free survival (PFS) in patients with recurrent, platinum-sensitive ovarian cancer when compared with sequential administration of these agents (Table). No difference in overall survival (OS) was observed, however, and patients on combination therapy experienced a somewhat decreased quality of life.

The study randomized 148 patients with platinum-sensitive recurrent ovarian, peritoneal, or tubal cancer to combination therapy (n = 74) or sequential therapy (n = 74); all patients had measurable disease and had received ≤1 prior chemotherapy regimen. The combination arm received docetaxel and carboplatin on day 1, followed by docetaxel on day 8, and the cycle was repeated every 3 weeks for 6 cycles. The sequential arm received docetaxel on days 1 and 8 every 3 weeks until evidence of disease progression or until completion of 6 cycles, after which patients started 6 cycles of carboplatin, administered on day 1 of each cycle.

What it did show, said Alvarez- Secord, was that “combination and sequential weekly docetaxel and carboplatin have activity in recurrent platinum-sensitive ovarian cancer.” She added, “Combination therapy may provide a PFS advantage over a planned sequential monotherapy.”

The overall response rate was 55.4% in the combination-therapy arm, with complete responses observed in 18% of patients; the sequential arm had a 43.2% overall response, with a 12.2% rate of complete response. Median PFS in patients who received the doublet was 13.7 months compared with 8.4 months for those in the sequential arm. This advantage for the combination regimen did not carry over to OS, which was 33.2 months in the combination arm versus 30.1 months in the sequential arm. Approximately 28% of patients in the combination arm achieved stable disease compared with 33.8% in the sequential arm.

Further, patients in the combination arm reported poorer quality of life, offsetting the benefit of improved PFS. Quality of life assessments were conducted through 6 cycles of therapy, and found a statistically significant advantage in the sequential therapy arm following the first cycle of therapy (P = .013).

This might be attributable to the higher rate of serious adverse effects experienced by patients in the combination therapy cohort. The rate of grade 3-4 neutropenia was nearly tripled in the combination arm, experienced by 37% of patients. Only 11% of patients who received the drugs sequentially developed grade 3-4 neutropenia. Grade 2 neurotoxicity was the same between groups, occurring in 9% of patients in each arm, which investigator Angeles Alvarez- Secord, MD, Duke University, Durham, North Carolina, described as “low.” No patients in the sequential arm experienced grade 3 neurotoxicity compared with 3% in the combination arm. In addition, approximately 50% of patients in the combination arm required erythropoietin-stimulating agents to treat anemia versus 34% in the sequential arm. Growth factor support was given to 22% of patients in the combination arm compared with 14% in the sequential arm.

The significance of the study results are unclear because the trial was initially designed to compare combination and sequential therapy but was modified to compare these treatment strategies separately against historical results after the study failed to accrue its targeted number of patients. What it did show, said Alvarez-Secord, was that “combination and sequential weekly docetaxel and carboplatin have activity in recurrent platinum-sensitive ovarian cancer.” She added, “Combination therapy may provide a PFS advantage over a planned sequential monotherapy.”

Alvarez-Secord A, et al. A multicenter, randomized, phase II study evaluating the efficacy and safety of combination docetaxel and carboplatin and sequential therapy with docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer. Presented at: Society of Gynecologic Oncologists. March 14-17, 2010; San Francisco, California.

For more information on available clinical trials in a variety of cancers, see the “Net Guide” section in this month’s issue of Oncology Net Guide.