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

Int J Gynecol Cancer. 2020 Dec;30(12):1915-1921. doi: 10.1136/ijgc-2020-001641. Epub 2020 Oct 26.

Abstract

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.

Keywords: ovarian cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carboplatin / administration & dosage
  • Cytoreduction Surgical Procedures
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Nivolumab / administration & dosage
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / surgery
  • Paclitaxel / administration & dosage
  • Polyethylene Glycols / administration & dosage
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Survival Rate

Substances

  • liposomal doxorubicin
  • Nivolumab
  • Polyethylene Glycols
  • Doxorubicin
  • Carboplatin
  • Paclitaxel