PMID- 27955684 OWN - NLM STAT- MEDLINE DCOM- 20170807 LR - 20181202 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 18 IP - 1 DP - 2016 Dec 13 TI - 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. PG - 126 LID - 126 AB - BACKGROUND: 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. METHODS: 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/m(2) initial dose, 30-35 mg/m(2) maintenance 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01565083 , registered on 26 March 2012. FAU - Perez, Edith A AU - Perez EA AD - US Medical Affairs, Genentech, Inc., South San Francisco, CA, 94080, USA. perez.edith@gene.com. FAU - Lopez-Vega, Jose Manuel AU - Lopez-Vega JM AD - Hospital Universitario Marques de Valdecilla, Santander, Spain. FAU - Petit, Thierry AU - Petit T AD - Department of Medical Oncology, Paul Strauss Cancer Center and University of Strasbourg, Strasbourg, France. FAU - Zamagni, Claudio AU - Zamagni C AD - Policlinico S. Orsola-Malpighi Hospital, Bologna, Italy. FAU - Easton, Valerie AU - Easton V AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Kamber, Julia AU - Kamber J AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Restuccia, Eleonora AU - Restuccia E AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Andersson, Michael AU - Andersson M AD - Department of Oncology, Rigshospitalet, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT01565083 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20161213 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Biomarkers, Tumor) RN - 5V9KLZ54CY (Vinblastine) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - K16AIQ8CTM (pertuzumab) RN - P188ANX8CK (Trastuzumab) RN - Q6C979R91Y (Vinorelbine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Biomarkers, Tumor MH - Breast Neoplasms/*drug therapy/*metabolism/mortality/pathology MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Receptor, ErbB-2/*metabolism MH - Retreatment MH - Survival Analysis MH - Trastuzumab/administration & dosage MH - Treatment Outcome MH - Vinblastine/administration & dosage/analogs & derivatives MH - Vinorelbine PMC - PMC5154110 OTO - NOTNLM OT - Locally advanced breast cancer OT - Metastatic breast cancer OT - Pertuzumab OT - Trastuzumab OT - Vinorelbine EDAT- 2016/12/14 06:00 MHDA- 2017/08/08 06:00 PMCR- 2016/12/13 CRDT- 2016/12/14 06:00 PHST- 2016/02/18 00:00 [received] PHST- 2016/10/25 00:00 [accepted] PHST- 2016/12/14 06:00 [entrez] PHST- 2016/12/14 06:00 [pubmed] PHST- 2017/08/08 06:00 [medline] PHST- 2016/12/13 00:00 [pmc-release] AID - 10.1186/s13058-016-0773-6 [pii] AID - 773 [pii] AID - 10.1186/s13058-016-0773-6 [doi] PST - epublish SO - Breast Cancer Res. 2016 Dec 13;18(1):126. doi: 10.1186/s13058-016-0773-6.