Combo Regimen Prolongs PFS/Hurts Quality of Life in Ovarian Cancer

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, but no difference in overall survival (OS) was observed, 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 undergone no more than one prior chemotherapy regimen. The combination arm received docetaxel on days 1 and 8 plus carboplatin on day 1, and the cycle was repeated every 3 weeks for six cycles. The sequential arm received docetaxel on days 1 and 8 every 3 weeks until there was disease progression or six cycles were completed, after which they received sequential carboplatin on day 1 for six cycles.

The overall response rate was 55.4% in the combination therapy arm, with complete responses observed in 18% of patients, whereas the sequential arm had a 43.2% overall response, with 12.2% complete responses. Although the response rate was increased with combination therapy, these patients experienced more severe side effects than those receiving sequential therapy, with a 37% incidence of grade 3-4 neutropenia versus 11% in the sequential arm. While grade 2 neurotoxicity was the same between groups, occurring in 9% of patients in each arm, no patients in the sequential arm experienced grade 3 neurotoxicity compared with 3% in the combination arm. In addition, approximately 50% of the combination arm required administration of erythropoietin-stimulating agents versus 34% in the sequential arm, and 22% in the combination arm received growth factor support versus 14% in the sequential arm.

Patients in the combination therapy arm had a median PFS of 13.7 months compared with 8.4 months for those in the sequential arm, but there was no significant difference in OS, with an OS of 33.2 months observed in the combination arm versus 30.1 months in the sequential arm. Further, the patients in the combination arm experienced a lower quality of life, offsetting the benefit of improved PFS. A quality of life assessment, conducted through six cycles of therapy, demonstrated a better quality of life among the sequential therapy arm following the first cycle of therapy, a finding that reached statistical significance (P = .013).

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. Future assessment will be needed to determine whether combining agents up front improves outcomes compared with administering them sequentially.