Paclitaxel with or without pazopanib for ovarian cancer relapsing during bevacizumab maintenance therapy: The GINECO randomized phase II TAPAZ study

Background Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab. Methods In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/m2 plus pazopanib 600–800 mg daily or standard weekly paclitaxel 80 mg/m2. The primary endpoint was 4-month progression-free survival (PFS) rate. Results Overall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51–73%] with the combination versus 68% [95% CI, 54–85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1–6.1] versus 5.8 [95% CI, 4.8–7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone. Conclusions In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery.ClinicalTrials.gov registration: NCT02383251.