Nintedanib Worsens Outcomes Along With Chemo in Advanced Ovarian Cancer

June 11, 2019

A phase II trial showed that the addition of nintedanib to neoadjuvant chemotherapy did not benefit patients with advanced epithelial ovarian cancer.

The addition of the VEGF/FGF/PDGF receptor inhibitor nintedanib to neoadjuvant chemotherapy (NACT) increased toxicity and worsened survival in patients with advanced epithelial ovarian cancer, according to a phase II trial.

“Neoadjuvant chemotherapy represents an alternative strategy for patients with stage IIIC or IV [ovarian cancer] who are considered not to be optimally resectable at primary surgery,” wrote study authors led by Gwenaël Ferron, of the Institut Claudius Regaud in Toulouse, France, in a poster. Previous work has suggested that nintedanib might offer advantages over bevacizumab when added to NACT, due to the latter agent’s long half-life and interference with wound healing.

Ferron presented results of the phase II CHIVA trial at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract 5512). The study included a total of 188 patients randomized to receive either nintedanib (124 patients) or placebo (64 patients), along with NACT (carboplatin and paclitaxel), followed by interval debulking surgery and then adjuvant chemotherapy along with either nintedanib or placebo. This was followed by 2 years of maintenance therapy with nintedanib or placebo.

The patients had a median age of approximately 64 years, and most patients had serous histology and FIGO stage III disease. Diagnostic surgery was done using laparoscopy in 92.7% of nintedanib patients and 94.7% of placebo patients.

The nintedanib group experienced more toxicity than the placebo group, with 92% reporting at least one grade 3 or 4 adverse event compared with 71% in the placebo group. The most common grade 3/4 adverse events included neutropenia (13.5% with nintedanib vs 6.7% with placebo), hypertension (12.6% vs 0%), and diarrhea (9.7% vs 1.6%).

More patients in the nintedanib group required a dose interruption of the study drug (45.9% vs 29.7%), and more patients also required dose reductions of carboplatin (13.7% vs 0%) or paclitaxel (4.0% vs 1.6%).

Response rates to NACT were lower with nintedanib, at 35.1% after 2 cycles compared with 55.9% with placebo (P = .0090). Interval debulking surgery was performed in only 69.9% of nintedanib patients compared with 81.7% of placebo patients.

The median progression-free survival with the study drug was 14.4 months, compared with 16.8 months with placebo, for a hazard ratio (HR) of 1.50 (P = .02). A similar result was seen for overall survival, with a median of 37.7 months with nintedanib and 44.1 months with placebo, for an HR of 1.54 (P = .053).

“The addition of nintedanib to neoadjuvant chemotherapy for advanced epithelial ovarian cancer increases toxicity and compromises chemotherapy efficacy, leading to a reduced rate of debulking surgery and worse progression-free survival and overall survival,” the authors concluded.

During a poster discussion session at ASCO, Debra L. Richardson, MD, of the Stephenson Cancer Center at the University of Oklahoma, agreed that the drug caused too much toxicity. “In this trial, more was worse,” she said. “I think we need to proceed with caution when adding additional agents to chemotherapy in the neoadjuvant setting.” She noted that just because an agent was added safely to chemotherapy in the adjuvant setting doesn’t necessarily mean it will provide an advantage in the neoadjuvant setting.