Background: Pertuzumab, trastuzumab, and docetaxel is standard of care for first-line treatment of HER2-positive\nmetastatic breast cancer (MBC). However, alternative chemotherapy partners are required to align with patient/\nphysician preferences and to increase treatment flexibility. We report VELVET Cohort 1 results in which the efficacy\nand safety of pertuzumab and trastuzumab, administered sequentially in separate infusions, followed by vinorelbine,\nwere evaluated. Cohort 2, where pertuzumab and trastuzumab were administered in a single infusion, followed by\nvinorelbine, recruited after Cohort 1 was fully enrolled, will be reported later.\nMethods: In this multicenter, two-cohort, open-label, phase II study, patients with HER2-positive locally advanced or\nMBC who had not received chemotherapy or biological therapy for their advanced disease received 3-weekly\npertuzumab (840 mg loading, 420 mg maintenance doses) and trastuzumab (8 mg/kg loading, 6 mg/kg maintenance\ndoses), followed by vinorelbine (25 mg/m2 initial dose, 30ââ?¬â??35 mg/m2 maintenance doses) on days 1 and 8 or 2 and 9\nof each 3-weekly cycle. Study treatment was given until investigator-assessed disease progression or unacceptable\ntoxicity. The primary endpoint was investigator-assessed objective response rate (ORR) in patients with measurable\ndisease at baseline per RECIST v1.1. Secondary endpoints included progression-free survival (PFS) and safety.\nResults: Cohort 1 enrolled 106 patients. Investigator-assessed ORR was 74.2% (95% CI 63.8ââ?¬â??82.9) in intent-to-treat\npatients with measurable disease (89/106 [84.0%]). Median PFS was 14.3 months (95% CI 11.2ââ?¬â??17.5) in the\nintent-to-treat population. Treatment was reasonably well tolerated, with no unexpected toxicities. Diarrhea\n(61/106 patients [57.5%]) and neutropenia (54/106 [50.9%]) were the most common adverse events (AEs);\nneutropenia (33/106 [31.1%]) and leukopenia (14/106 [13.2%]) were the most common grade ââ?°Â¥3 AEs. Serious\nAEs were reported in 32/106 (30.2%) patients. AEs led to study drug discontinuation in 36/106 patients\n(34.0%). Eighteen of 106 patients (17.0%) had AEs suggestive of congestive heart failure; however, there were no\nconfirmed cases.\nConclusions: The vinorelbine, pertuzumab, and trastuzumab combination is active and reasonably well tolerated.\nThis regimen offers an alternative for patients who cannot receive docetaxel for first-line treatment of HER2-positive\nlocally advanced or MBC.
Loading....