First Trial Assessing Nivolumab in Platinum-Resistant Ovarian Cancer

Conference Correspondent - ASCO 2014 - Immuno-Oncology

The majority of women diagnosed with ovarian epithelial cancer (80%) relapse after first-line platinum- and taxane-based chemotherapy. Clinical recurrences within 6 months of completion of platinum-containing therapy are described as platinum-refractory or platinum-resistant.1 Current options for management of platinum-resistant ovarian cancer (PROC) include cytotoxic agents, such as anthracyclines (including pegylated liposomal doxorubicin), taxanes, topotecan, and gemcitabine.1

Outcomes for women with PROC remain very poor. When compared in a large phase 3 trial in PROC, liposomal doxorubicin and topotecan were found to have comparable response rates (20% vs 17%), progression-free survival (PFS) (16 vs 17 weeks), and overall survival (OS) (60 vs 58 weeks).3 Long-term follow-up showed OS outcomes remained similar when comparing patients with PROC who received liposomal doxorubicin or topotecan.4

In 2007, Hamanishi et al published translational research indicating that ovarian cancer cell expression of PD-L1 correlates with prognosis, such that PD-1 and PD-L1 pathways may be a viable target in ovarian cancer.2 On the basis of these findings, Hamanishi and colleagues (ASCO 2014; Abstract 5511) are currently studying the efficacy and safety of nivolumab (NIV), an anti-PD-1 antibody, in patients with PROC.

Women who have enrolled in the NIV protocol to date have been highly pretreated (median of 4 prior cytotoxic treatments) with a disproportionate number of patients with clear cell histology, a known contributor to treatment resistance. NIV was administered every 2 weeks to patients at a dose of either 1 or 3 mg/kg. Patients received NIV up to 6 cycles (4 doses per cycle) or until disease progression. Response rate was assessed by RECIST v1.1.

To date, 18 patients with PROC have been treated with NIV on this protocol (1 mg/kg: n = 10; 3 mg/kg: n = 8). The most frequent adverse events (AEs) observed included rash, increased liver enzymes, hypothyroidism, fever, arthralgia, low albumin, and lymphocytopenia, but these did not appear to be dose-related. One patient taking 1 mg/kg of NIV experienced severe AEs, including fever, disorientation, and gait disturbance. A patient taking 3 mg/kg of NIV experienced fever and a grade 3 deep vein thrombosis, but responded to NIV and continues on therapy.

Clinical response rates observed with NIV in this trial are shown in the Table.

Table: Efficacy Outcomes with NIV in Patients with PROC (n = 18)

1 mg/kg 10 0 1 2 3 1 1/10 (10%) 3/10 (30%);
3 mg/kg 8 2 0 3 3 0 2/8 (25%) 5/8 (63%)
Total 18 2 1 5 9 1 3/18 (17%) 8/18 (44%)

RR indicates response rate (complete response [CR] + partial response [PR]); DCR, disease control rate (CR + PR + stable disease [SD]).

After assessing 18 of 20 planned patients for this phase 1 study, Hamanashi and colleagues concluded that both doses of NIV (1 and 3 mg/kg) are well tolerated and have encouraging clinical efficacy for patients with recurrent PROC, with the 3-mg/kg dose appearing more favorable. Biomarkers of response and AEs are being explored.


  1. National Cancer Institute website. Ovarian Epithelial Cancer Treatment: PDQ®. Recurrent or Persistent Ovarian Epithelial Cancer Treatment. Last modified: January 31, 2014. Accessed June 1, 2014.
  2. Hamanishi J1, Mandai M, Iwasaki M, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007;104(9):3360-3365.
  3. Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19(14):3312-3322.
  4. Gordon AN, Tonda M, Sun S, et al. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004;95(1):1-8.