Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial

Authors

Jacobus Pfisterer

¹Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group and Gynecologic Oncology Center, Kiel, Germany

Jacobus Pfisterer, Florence Joly, Gunnar Kristensen, Joern Rau, Sven Mahner, Patricia Pautier, Ahmed El-Balat, Jean-Emmanuel Kurtz, Ulrich Canzler, Jalid Sehouli, Martin L. Heubner, Andreas D. Hartkopf, Klaus Baumann, Annette Hasenburg, Lars C. Hanker, Antje Belau, Barbara Schmalfeldt, Dominik Denschlag, Tjoung-Won Park-Simon, Frédéric Selle, Christian Jackisch, Alexander Burges, Hans-Joachim Lück, Günter Emons, Werner Meier, Martina Gropp-Meier, Willibald Schröder, Nikolaus de Gregorio, Felix Hilpert, Philipp Harter

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PURPOSE

To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer.

In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m² plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability.

Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab.

Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.