Pre-operative neoadjuvant chemotherapy cycles and survival in newly diagnosed ovarian cancer: what is the optimal number? A Memorial Sloan Kettering Cancer Center Team Ovary study

Objective Although trials of neoadjuvant chemotherapy in ovarian cancer use 3 neoadjuvant cycles, real-world practice varies. We sought to evaluate the influence of increasing pre-operative cycles on survival, accounting for surgical outcomes. Methods We identified 199 women with newly diagnosed ovarian cancer recommended for neoadjuvant chemotherapy who underwent interval debulking surgery from July 2015 to December 2018. Non-parametric tests were used to compare clinical characteristics by neoadjuvant cycles. The Kaplan-Meier method was used to estimate differences in progression-free and overall survival. The log-rank test was used to assess the relationship of covariates to outcome. Results The median number of neoadjuvant cycles was 4 (range 3-8), with 56 (28%) women receiving >= 5 cycles. Compared with those receiving 3 or 4, women with >= 5 neoadjuvant cycles received fewer or no post-operative cycles (p<0.001) but had no other differences in clinical factors (p>0.05). Complete gross resection rates were similar among those receiving 3, 4, and >= 5 neoadjuvant cycles (68.5%, 70%, and 71.4%, respectively, p=0.96). There were no significant differences in progression-free or overall survival when comparing 3 versus 4 neoadjuvant cycles. However, more cycles (>= 5 vs 4) were associated with worse progression-free survival, even after adjustment for BRCA status and complete gross resection (HR 2.20, 95% CI 1.45 to 3.33, p<0.001), and worse overall survival, even after adjustment for histology, response on imaging, and complete gross resection rates (HR 2.78, 95% CI 1.37 to 5.63, p=0.016). The most common reason for receiving >= 5 cycles was extent of disease requiring more neoadjuvant chemotherapy. Conclusions Despite maximal cytoreduction, patients receiving >= 5 neoadjuvant cycles have a poorer prognosis than those receiving 3-4 cycles. Future studies should focus on reducing surgical morbidity and optimizing novel therapies in this high-risk group.