RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer
MetadataShow full item record
© 2017. Introduction: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status. Patients and Methods: A total of 537 patients were randomized to capecitabine 1000 mg/m 2 orally twice per day for days 1 to 14 every 21 days with oral sorafenib 600 mg/d or placebo. The primary end point was progression-free survival (PFS). Patients were stratified according to hormone receptor status, previous chemotherapies for metastatic breast cancer, and geographic region. Results: Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI] , 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%). Conclusion: The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm.
Showing items related by title, author, creator and subject.
Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trialChan, Arlene; Delaloge, S.; Holmes, F.; Moy, B.; Iwata, H.; Harvey, V.; Robert, N.; Silovski, T.; Gokmen, E.; von Minckwitz, G.; Ejlertsen, B.; Chia, S.; Mansi, J.; Barrios, C.; Gnant, M.; Buyse, M.; Gore, I.; Smith, J.; Harker, G.; Masuda, N.; Petrakova, K.; Zotano, A.; Iannotti, N.; Rodriguez, G.; Tassone, P.; Wong, A.; Bryce, R.; Ye, Y.; Yao, B.; Martin, M. (2016)Background: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of ...
Chan, Arlene; Verrill, M. (2009)Background - As anthracyclines and taxanes are frequently used in the adjuvant and first-line metastatic settings, capecitabine and vinorelbine are frequently used as monotherapy and in combination for metastatic breast ...
Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trialMartin, M.; Holmes, F.; Ejlertsen, B.; Delaloge, S.; Moy, B.; Iwata, H.; von Minckwitz, G.; Chia, S.; Mansi, J.; Barrios, C.; Gnant, M.; Tomaševic, Z.; Denduluri, N.; Šeparovic, R.; Gokmen, E.; Bashford, A.; Ruiz Borrego, M.; Kim, S.; Jakobsen, E.; Ciceniene, A.; Inoue, K.; Overkamp, F.; Heijns, J.; Armstrong, A.; Link, J.; Joy, A.; Bryce, R.; Wong, A.; Moran, S.; Yao, B.; Xu, F.; Auerbach, A.; Buyse, M.; Chan, Arlene; ExteNET Study Group (2017)Background: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with ...