Journal Article

Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): an open-label, multicenter, phase II trial

Jin, Xidong, Vladimirov, Vladimir, Huang, Chiun-Sheng, Yang, Youngsen, Pemberton, Karine, Hickish, Tamas, Chang, Yuan-Ching, Tsang, Janice, Tseng, Ling-Ming, Arora, Rajendra Singh, Jain, Minish, Sadrolhefazi, Behbood, Liu, Mei-Ching, Mehta, Ajay

2022

Overview

Purpose Resistance to HER2 (ErbB2)-targeted therapy may be mediated by other members of the ErbB family. We investigated the efficacy and safety of the irreversible ErbB family blocker, afatinib, alone as first-line therapy in the advanced setting and in combination with vinorelbine or paclitaxel for those who progressed on afatinib monotherapy, in female patients with metastatic breast cancer who had failed or progressed on prior HER2-targeted therapy in the early disease setting. Methods In this phase II, single-arm, two-part study (ClinicalTrials.gov: NCT01271725), patients in part A received afatinib 40 mg/day in 21-day cycles until disease progression or intolerable adverse events (AEs). Patients with progressive disease could then receive afatinib plus weekly vinorelbine 25 mg/m 2 or paclitaxel 80 mg/m 2 until disease progression or intolerable AEs (part B). The primary endpoint was confirmed objective response rate (RECIST v1.1). Results Eighty-seven patients were enrolled and 74 were treated in part A (median age: 51 years [range 27–76]; 31 [42%] estrogen receptor-positive, 26 [35%] progesterone receptor-positive). Of these, 39 (53%) patients went on to receive afatinib plus vinorelbine (13 patients) or paclitaxel (26 patients) in part B. Thirteen (18%) and 12 (31%) patients achieved an objective response in parts A and B, respectively. The most common treatment-related AEs with afatinib monotherapy (any/grade ≥ 3) were diarrhea (68%/8%) and rash (49%/4%). Combination therapy was generally well tolerated, with no additive toxicity observed. Conclusion Afatinib treatment, alone or in combination with vinorelbine or paclitaxel, was associated with objective responses in ≥ 18% of patients with metastatic breast cancer for whom prior HER2-targeted therapy has failed. Treatment-related AEs were generally manageable, with few grade ≥ 3 AEs reported. Trial registration ClinicalTrials.gov, NCT01271725, registered 1 July 2011.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Adult / Afatinib - adverse effects / Aged / Antimitotic agents / Antineoplastic agents / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Cancer patients / Cancer research / Care and treatment / Clinical Trial / Clinical trials / Complications and side effects / Diarrhea / ErbB protein / ErbB-2 protein / Estrogen / Estrogen receptors / Female / Health aspects / Humans / Inhibitor drugs / Lapatinib - therapeutic use / Medical colleges / Medicine / Medicine & Public Health / Metastases / Metastasis / Middle Aged / Monoclonal antibodies / Oncology / Paclitaxel / Patients / Product development / Progesterone / Quinazolines / Receptor, ErbB-2 - genetics / Targeted cancer therapy / Toxicity / Trastuzumab / Treatment Outcome / Vinorelbine / Vinorelbine - therapeutic use / Women