Continued chemotherapy after complete response to primary therapy among women with advanced ovarian cancer

Ovarian cancer (OC) has the highest mortality rate of all cancers of the reproductive system, and is the fourth leading cause of cancer-related death among women.1 Women with OC are faced with a 5-year survival rate of 46% for all stages, which drops to 31% for advanced disease.1 Since the 1970s, treatment advances have led to <5 months improvement in overall survival among women with OC.2 The majority of OC patients respond to primary therapy consisting of debulking surgery followed by platinum and taxane-based chemotherapy. However, most women recur, and recurrent OC is invariably fatal. Thus, significant effort has been dedicated to improving the outcome of primary therapy to avoid recurrences, including increased intensity of primary chemotherapy,3,4 addition of new agents to the standard regimen,5 or continuation of primary therapy in the form of either consolidation or maintenance therapy.6,7 In general, consolidation therapy is designed to be a short-term treatment boost after initial therapy to consolidate the initial response to therapy.8 Maintenance therapy is designed to maintain the disease-free period as long as possible, while delivering a reduced dose of chemotherapy over a longer period of time (eg, 6 cycles or more).7 It has been speculated that continued reduction of residual cancer cells by extending the period of chemotherapy administration will diminish the risk of tumor regrowth. The concept of maintenance therapy has its roots in the experience extracted from the treatment of acute lymphoblastic leukemias, where postremission therapy continued to reduce the burden of residual cancer cells, eventually yielding eradication of the disease.9,10 Although this hypothesis has not yet been validated experimentally in solid tumors, the emergence of the cancer stem cell theory11,12 further supports the idea that residual cancer cells with stem cell properties persist after completion of chemotherapy and eventually give rise to recurrent metastases that recapitulate the characteristics of the original tumor. This concept strengthens the rationale for investigating postremission therapy to eradicate residual chemotherapy-resistant tumors. The purpose of this meta-analysis was to pool and analyze the existent data on consolidation and maintenance therapy in OC. The largest and most compelling randomized trial conducted to test this theory evaluated 12 versus 3 cycles of monthly paclitaxel as maintenance therapy in OC patients in first remission.7 At the time of a planned interim analysis, the Southwest Oncology Group Data and Safety Monitoring Committee noted significant differences in progression-free survival (PFS) and recommended study closure.7 As a result, enrollment was halted, which led to a reduction in the statistical power to detect an overall survival (OS) benefit.13 Another nonrandomized small study using the same regimen as the Southwest Oncology Group trial recorded improved PFS in patients receiving 12 cycles of therapy compared with controls (11 vs 24 months, P = .0062) and an improved median OS (38 months vs not reached; P =.0019).14 On the contrary, a randomized trial of 6 courses of monthly paclitaxel versus no further treatment found no significant improvement in PFS or OS, but this study was also underpowered.15 Those and other studies’ discrepant results led to unclear interpretation of the data for application in clinical practice.16–18 As a result, the choice of whether to pursue continued therapy is generally made based on the physician’s own viewpoint about its value. To address these inconclusive data, a meta-analysis was conducted to assess the impact of consolidation and maintenance therapy on survival and toxicity outcomes among patients with OC in first remission.