title: Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results.
abstract: Pertuzumab, trastuzumab, and docetaxel is standard of care for first-line treatment of HER2-positive metastatic breast cancer (MBC). However, alternative chemotherapy partners are required to align with patient/physician preferences and to increase treatment flexibility. We report VELVET Cohort 1 results in which the efficacy and safety of pertuzumab and trastuzumab, administered sequentially in separate infusions, followed by vinorelbine, were evaluated. Cohort 2, where pertuzumab and trastuzumab were administered in a single infusion, followed by vinorelbine, recruited after Cohort 1 was fully enrolled, will be reported later.
  
  
  
  In this multicenter, two-cohort, open-label, phase II study, patients with HER2-positive locally advanced or MBC who had not received chemotherapy or biological therapy for their advanced disease received 3-weekly pertuzumab (840 mg loading, 420 mg maintenance doses) and trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses), followed by vinorelbine (25 mg/m2initial dose, 30-35 mg/m2maintenance doses) on days 1 and 8 or 2 and 9 of each 3-weekly cycle. Study treatment was given until investigator-assessed disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) in patients with measurable disease at baseline per RECIST v1.1. Secondary endpoints included progression-free survival (PFS) and safety.
  
  
  
  Cohort 1 enrolled 106 patients. Investigator-assessed ORR was 74.2% (95% CI 63.8-82.9) in intent-to-treat patients with measurable disease (89/106 [84.0%]). Median PFS was 14.3 months (95% CI 11.2-17.5) in the intent-to-treat population. Treatment was reasonably well tolerated, with no unexpected toxicities. Diarrhea (61/106 patients [57.5%]) and neutropenia (54/106 [50.9%]) were the most common adverse events (AEs); neutropenia (33/106 [31.1%]) and leukopenia (14/106 [13.2%]) were the most common grade ≥3 AEs. Serious AEs were reported in 32/106 (30.2%) patients. AEs led to study drug discontinuation in 36/106 patients (34.0%). Eighteen of 106 patients (17.0%) had AEs suggestive of congestive heart failure; however, there were no confirmed cases.
  
  
  
  The vinorelbine, pertuzumab, and trastuzumab combination is active and reasonably well tolerated. This regimen offers an alternative for patients who cannot receive docetaxel for first-line treatment of HER2-positive locally advanced or MBC.
  
  
  
  ClinicalTrials.gov: NCT01565083 , registered on 26 March 2012.
authors.affiliation: US Medical Affairs, Genentech, Inc., South San Francisco, CA, 94080, USA. perez.edith@gene.com.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: López-Vega
authors.affiliation: Department of Medical Oncology, Paul Strauss Cancer Center and University of Strasbourg, Strasbourg, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Petit
authors.affiliation: Policlinico S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Easton
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Kamber
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Restuccia
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D019233:Retreatment; D016019:Survival Analysis; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine; C485206:pertuzumab
keywords: Locally advanced breast cancer; Metastatic breast cancer; Pertuzumab; Trastuzumab; Vinorelbine