Eric Pujade-Lauraine1, Frédéric Selle2, Béatrice Weber2, Isabelle-Laure Ray-Coquard2, Ignace Vergote2, Jozef Sufliarsky2, Josep Maria Del Campo2, Alain Lortholary2, Anne Lesoin2, Philippe Follana2, Gilles Freyer2, Beatriz Pardo2, Laura Vidal2, Bengt Tholander2, Laurence Gladieff2, Mouna Sassi2, Pilar Garin-Chesa2, Serge Nazabadioko2, Kristell Marzin2, Korinna Pilz2, Florence Joly2. 1. Eric Pujade-Lauraine, Centre des Cancers de la Femme et Recherche Clinique, Paris; Frédéric Selle, Hôpitaux Universitaires de l'Est Parisien-site Tenon and Alliance Pour la Recherche En Cancérologie, Paris; Béatrice Weber, Centre Alexis Vautrin, Vandoeuvre-les-Nancy; Isabelle-Laure Ray-Coquard, Centre Léon Bérard and Université Claude Bernard-Lyon I, Lyon; Alain Lortholary, Centre Catherine de Sienne, Nantes; Anne Lesoin, Centre Oscar Lambret, Lille; Philippe Follana, Centre Antoine-Lacassagne, Nice; Gilles Freyer, Lyon University, Hospices Civils de Lyon, Pierre-Bénite Cédex; Laurence Gladieff, Institut Claudius Regaud-IUCTO, Toulouse; Mouna Sassi and Serge Nazabadioko, Boehringer Ingelheim, Reims; Florence Joly, Centre François Baclesse, Caen, France; Ignace Vergote, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Jozef Sufliarsky, National Cancer Institute, Bratislava, Slovakia; Josep Maria Del Campo, Hospital University, Vall d'Hebrón; Beatriz Pardo, Institut Català d'Oncologia-Instituto de Investigación Biomédica de Bellvitge; Laura Vidal, Hospital Clínic de Barcelona, Barcelona, Spain; Bengt Tholander, Uppsala University Hospital, Uppsala, Sweden; Pilar Garin-Chesa, Boehringer Ingelheim, Vienna, Austria; Kristell Marzin, Boehringer Ingelheim, Biberach; and Korinna Pilz, Boehringer Ingelheim, Ingelheim, Germany. epujade@arcagy.org. 2. Eric Pujade-Lauraine, Centre des Cancers de la Femme et Recherche Clinique, Paris; Frédéric Selle, Hôpitaux Universitaires de l'Est Parisien-site Tenon and Alliance Pour la Recherche En Cancérologie, Paris; Béatrice Weber, Centre Alexis Vautrin, Vandoeuvre-les-Nancy; Isabelle-Laure Ray-Coquard, Centre Léon Bérard and Université Claude Bernard-Lyon I, Lyon; Alain Lortholary, Centre Catherine de Sienne, Nantes; Anne Lesoin, Centre Oscar Lambret, Lille; Philippe Follana, Centre Antoine-Lacassagne, Nice; Gilles Freyer, Lyon University, Hospices Civils de Lyon, Pierre-Bénite Cédex; Laurence Gladieff, Institut Claudius Regaud-IUCTO, Toulouse; Mouna Sassi and Serge Nazabadioko, Boehringer Ingelheim, Reims; Florence Joly, Centre François Baclesse, Caen, France; Ignace Vergote, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Jozef Sufliarsky, National Cancer Institute, Bratislava, Slovakia; Josep Maria Del Campo, Hospital University, Vall d'Hebrón; Beatriz Pardo, Institut Català d'Oncologia-Instituto de Investigación Biomédica de Bellvitge; Laura Vidal, Hospital Clínic de Barcelona, Barcelona, Spain; Bengt Tholander, Uppsala University Hospital, Uppsala, Sweden; Pilar Garin-Chesa, Boehringer Ingelheim, Vienna, Austria; Kristell Marzin, Boehringer Ingelheim, Biberach; and Korinna Pilz, Boehringer Ingelheim, Ingelheim, Germany.
Abstract
PURPOSE: Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. PATIENTS AND METHODS: Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator's choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. RESULTS: Of the 109 patients receiving treatment, 54 received volasertib and 55 receivedchemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. CONCLUSION: Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.
RCT Entities:
PURPOSE:Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. PATIENTS AND METHODS: Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator's choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. RESULTS: Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. CONCLUSION: Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.
Authors: Ming Zhang; Ratnakar Singh; Shaohua Peng; Tuhina Mazumdar; Vaishnavi Sambandam; Li Shen; Pan Tong; Lerong Li; Nene N Kalu; Curtis R Pickering; Mitchell Frederick; Jeffrey N Myers; Jing Wang; Faye M Johnson Journal: Cancer Lett Date: 2017-01-23 Impact factor: 8.679