Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus (Reolysin®) in recurrent ovarian, tubal, or peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study

Gynecol Oncol. 2017 Sep;146(3):477-483. doi: 10.1016/j.ygyno.2017.07.135. Epub 2017 Jul 27.

Abstract

Objective: To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer.

Patients and methods: Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80mg/m2 intravenously days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m2 intravenously days 1, 8, and 15) plus reovirus 3×1010TCID50/day intravenously on days 1-5, both every 4weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%.

Results: The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P=0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade≥4, 12% versus 0%), and severe respiratory adverse events (grade≥3, 25% versus 2%). No deaths were considered treatment related.

Conclusion: The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.

Keywords: Oncolytic virus; Paclitaxel; Recurrent ovarian cancer.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinoma / therapy*
  • Carcinoma, Ovarian Epithelial
  • Combined Modality Therapy / adverse effects
  • Disease-Free Survival
  • Fallopian Tube Neoplasms / therapy*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasms, Glandular and Epithelial / therapy*
  • Neutropenia / etiology
  • Oncolytic Virotherapy* / adverse effects
  • Oncolytic Viruses
  • Ovarian Neoplasms / therapy*
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use*
  • Peritoneal Neoplasms / therapy*
  • Prospective Studies
  • Reoviridae
  • Respiratory Tract Diseases / etiology

Substances

  • Antineoplastic Agents, Phytogenic
  • Paclitaxel