Ipilimumab Plus Nivolumab Improved Tumor Responses in Recurrent Ovarian Cancer

David Bai

A phase 2 trial evaluating the 2 checkpoint inhibitors, nivolumab and ipilimumab, found significantly better tumor responses with the combination compared with nivolumab alone in patients with recurrent epithelial ovarian cancer.
Ovarian cancer is the fifth leading cause of cancer in women and leads the charts in deaths from cancers associated with the female reproductive system. About 75% of all cases of ovarian cancer are diagnosed with advanced stage cancer (III or IV). Patients with low residual disease after surgical debulking have a risk of recurrence of 60% to 70%, with the risk of recurrence up to 85% in large-volume residual disease. 

While immunotherapy is a novel treatment option that has already been implemented in many cancers, including ovarian cancer, traditional treatment has been platinum-based chemotherapy.

Treatment options for patients in need of systemic treatments after relapse are classified into 2 main categories: platinum sensitive and platinum resistant. Platinum-sensitive patients are those who relapsed after 6 or more months of completing their initial platinum therapy likewise, platinum-resistant patients are patients who relapsed after less than 6 months of completing their initial platinum therapy.1

Immunotherapy is shown to be effective in recurrent ovarian cancer but needs further research. Checkpoint inhibitors, while an effective option, are only briefly mentioned for use under certain circumstances: pembrolizumab can be used in patients with microsatellite instability-high or mismatch repair-deficient solid tumors. Nivolumab is another checkpoint inhibitor shown to have some efficacy in this population. Trial results from NRG-GY003 (NCT02498600) evaluated the effectiveness of combination immunotherapy with ipilimumab and nivolumab versus nivolumab monotherapy.2

In this trial, women with recurrent epithelial ovarian cancer were randomized to receive treatment with either ipilimumab, a monoclonal antibody targeting CTLA-4, and nivolumab, a PD-1 inhibitor, or nivolumab alone for 6 months. After 6 months, there were 6 (12.2%) tumor responses in the nivolumab group, although there were 16 (34.1%) responses in the nivolumab and ipilimumab group (P= .034). The hazard ratio for progression-free survival and death were 0.599 (95% CI, 0.388-0.925) and 0.712 (95% CI, 0.393-1.291), respectively. More adverse events were seen in the nivolumab and ipilimumab group, but none lead to treatment-related deaths. 

From this trial, combination immunotherapy with CTLA-4 and PD-1 targeted therapy was found to be superior to PD-1 monotherapy alone. Future trials comparing nivolumab and ipilimumab with conventional chemotherapy will be needed to determine the role of immunotherapy in recurrent epithelial ovarian cancer. 

  1. Francis J, Coakley N, Elit L, Mackay H, and The Gynecologic Cancer Disease Site Group. Systemic therapy for recurrent epithelial ovarian cancer: a clinical practice guideline. Curr Oncol. 2017;24(6):e540-e546. doi: 10.3747/co.24.3824.
  2. Burger R, Sill M, Zamarin D, et al. NRG oncology phase 2 randomized trial of nivolumab with or without ipilimumab in patients with persistent or recurrent ovarian cancer. Abstract presented at the Biennial Meeting of the International Gynecological Cancer Society; 2018; Kyoto, Japan.
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