Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study - 03/08/11
, Henri Roche, ProfMD b, Tamas Pinter, MD c, John Crown, ProfMD c, M John Kennedy, MB d, Louise Provencher, MD e, Frank Priou, MD f, Wolfgang Eiermann, ProfMD g, Encarna Adrover, MD a, Istvan Lang, ProfMD h, Manuel Ramos, MD a, Jean Latreille, FRCPC i, Agnieszka Jagiełło-Gruszfeld, MD j, Tadeusz Pienkowski, MD k, Emilio Alba, MD a, Raymond Snyder, MMed l, Sachin Almel, MD m, Janusz Rolski, MD n, Montserrat Munoz, MD a, Rebecca Moroose, MD o, Sara Hurvitz, MD p, Ana Baños, BSc q, Henry Adewoye, MD r, Yong-Jiang Hei, MD r, Mary-Ann Lindsay, PhD s, Matthieu Rupin, MSc t, David Cabaribere, MSc t, Yasmin Lemmerick, MBA s, John R Mackey, ProfMD uon behalf of the TRIO 010 investigators
Summary |
Background |
Vascular endothelial growth factor (VEGF) has a crucial role in angiogenesis, and is a valid target in metastatic breast cancer. Motesanib is an investigational oral inhibitor of VEGF receptors. We aimed to determine whether treatment with motesanib plus paclitaxel is better than placebo plus paclitaxel in patients with HER2-negative locally recurrent or metastatic breast cancer.
Methods |
Between Dec 1, 2006, and July 4, 2008, patients with untreated HER2-negative metastatic breast cancer were randomly assigned (using a randomisation list created by personnel not associated with the study) in a 1:1:1 ratio to paclitaxel (90 mg/m2 on days 1, 8, and 15 every 3 weeks) plus either masked motesanib 125 mg orally once per day (n=91), masked placebo orally once per day (n=94), or open-label bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=97), after stratification according to adjuvant or neoadjuvant chemotherapy (taxane-containing regimens vs other regimens vs none), number of metastatic sites (<3 vs ≥3), and hormone receptor status (positive vs negative). Placebo was provided as a replica of motesanib 25 mg tablets. The primary endpoint was objective response rate (ORR) based on the population as assigned to treatment. This trial is registered with ClinicalTrials.gov, number NCT00356681.
Findings |
ORRs for the motesanib group and the placebo group did not differ significantly (49% vs 41%; absolute difference 8% [95% CI −6 to 22]; p=0·31). The ORR in the bevacizumab group (52%) was similar to that in the motesanib group. The most common grade 3 or higher adverse events included diarrhoea (18 of 92 patients in the motesanib group, none of 89 patients in the placebo group, and four of 96 patients in the bevacizumab group), fatigue (11, eight, and six), hypertension (11, one, and seven), and peripheral sensory neuropathy (ten, seven, and 19). More patients in the motesanib group had serious adverse events than did those in the placebo or bevacizumab groups (34, 26, and 21 patients, respectively); the most common of these in the motesanib group were gastrointestinal in nature.
Interpretation |
Data from this trial do not support the further investigation of motesanib at this dose and schedule in this population.
Funding |
Amgen.
Le texte complet de cet article est disponible en PDF.Plan
Vol 12 - N° 4
P. 369-376 - avril 2011 Retour au numéro
Article précédent
- Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study
- Stephen M Ansell, Hui Tang, Paul J Kurtin, Patricia A Koenig, David J Inwards, Keith Shah, Steven C Ziesmer, Andrew L Feldman, Radha Rao, Mamta Gupta, Charles Erlichman, Thomas E Witzig
- A 3′-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis
- Trupti Paranjape, Helen Heneghan, Robert Lindner, Florence K Keane, Aaron Hoffman, Antoinette Hollestelle, Jemima Dorairaj, Kimberly Geyda, Cory Pelletier, Sunitha Nallur, John WM Martens, Maartje J Hooning, Michael Kerin, Daniel Zelterman, Yong Zhu, David Tuck, Lyndsay Harris, Nicola Miller, Frank Slack, Joanne Weidhaas
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?