Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): A randomised, open-label, phase 2 trial

Sandro Pignata, Domenica Lorusso, Giovanni Scambia, Daniela Sambataro, Stefano Tamberi, Saverio Cinieri, Anna M. Mosconi, Michele Orditura, Alba A. Brandes, Valentina Arcangeli, Pierluigi Beneditti Panici, Carmela Pisano, Sabrina C. Cecere, Marilena Di Napoli, Francesco Raspagliesi, Giuseppa Maltese, Vanda Salutari, Caterina Ricci, Gennaro Daniele, Maria Carmela PiccirilloMassimo Di Maio, Ciro Gallo, Francesco Perrone

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer. Methods: We did this open-label, randomised phase 2 trial at 11 hospitals in Italy. We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy, Eastern Cooperative Oncology Group performance status 0-1, and no residual peripheral neurotoxicity. Patients were randomly assigned (1:1) to receive weekly paclitaxel 80 mg/m2 with or without pazopanib 800 mg daily, and stratified by centre, number of previous lines of chemotherapy, and platinum-free interval status. The primary endpoint was progression-free survival, assessed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01644825. This report is the final analysis; the trial is completed. Findings: Between Dec 15, 2010, and Feb 8, 2013, we enrolled 74 patients: 37 were randomly assigned to receive paclitaxel and pazopanib and 37 were randomly assigned to receive paclitaxel only. One patient, in the paclitaxel only group, withdrew from the study and was excluded from analyses. Median follow-up was 16·1 months (IQR 12·5-20·8). Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group (median 6·35 months [95% CI 5·36-11·02] vs 3·49 months [2·01-5·66]; hazard ratio 0·42 [95% CI 0·25-0·69]; p=0·0002). We recorded no unexpected toxic effects or deaths from toxic effects. Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group. The most common grade 3-4 adverse events were neutropenia (11 [30%] in the pazopanib group vs one [3%] in the paclitaxel group), fatigue (four [11%] vs two [6%]), leucopenia (four [11%] vs one [3%]), hypertension (three [8%] vs none [0%]), raised aspartate aminotransferase or alanine aminotransferase (three [8%] vs none), and anaemia (two [5%] vs five [14%]). One patient in the pazopanib group had ileal perforation. Interpretation: Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted. Funding: National Cancer Institute of Napoli and GlaxoSmithKline.

Original languageEnglish
Pages (from-to)561-568
Number of pages8
JournalThe Lancet Oncology
Volume16
Issue number5
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): A randomised, open-label, phase 2 trial'. Together they form a unique fingerprint.

Cite this