PMID- 35138529 OWN - NLM STAT- MEDLINE DCOM- 20220330 LR - 20220531 IS - 1573-7217 (Electronic) IS - 0167-6806 (Print) IS - 0167-6806 (Linking) VI - 192 IP - 3 DP - 2022 Apr TI - 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. PG - 593-602 LID - 10.1007/s10549-021-06449-4 [doi] AB - 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. CI - (c) 2022. The Author(s). FAU - Hickish, Tamas AU - Hickish T AUID- ORCID: 0000-0001-6770-7279 AD - Royal Bournemouth Hospital/Bournemouth University, Castle Ln E, Bournemouth, BH7 7DW, UK. tamas.hickish@rbch.nhs.uk. FAU - Mehta, Ajay AU - Mehta A AD - Central India Cancer Research Institute, Nagpur, India. FAU - Liu, Mei-Ching AU - Liu MC AD - Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan. FAU - Huang, Chiun-Sheng AU - Huang CS AD - National Taiwan University Hospital, Taipei, Taiwan. FAU - Arora, Rajendra Singh AU - Arora RS AD - Sujan Cancer & Surgical Hospital, Amravati, India. FAU - Chang, Yuan-Ching AU - Chang YC AD - Mackay Memorial Hospital, Taipei, Taiwan. FAU - Yang, Youngsen AU - Yang Y AD - Division of Hematology-Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Internal Medicine, College of Medicine, China Medical University, Taichung, Taiwan. FAU - Vladimirov, Vladimir AU - Vladimirov V AD - Pyatigorsk Oncology Dispensary, Pyatigorsk, Russia. FAU - Jain, Minish AU - Jain M AD - Ruby Hall Clinic, Pune, Maharashtra, India. FAU - Tsang, Janice AU - Tsang J AD - Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong. FAU - Pemberton, Karine AU - Pemberton K AD - Boehringer Ingelheim Ltd, Bracknell, UK. FAU - Sadrolhefazi, Behbood AU - Sadrolhefazi B AD - Boehringer Ingelheim Canada Ltd, Burlington, ON, Canada. FAU - Jin, Xidong AU - Jin X AD - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA. FAU - Tseng, Ling-Ming AU - Tseng LM AD - Taipei Veterans General Hospital, Taipei, Taiwan. LA - eng SI - ClinicalTrials.gov/NCT01271725 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20220209 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Quinazolines) RN - 0VUA21238F (Lapatinib) RN - 41UD74L59M (Afatinib) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P188ANX8CK (Trastuzumab) RN - P88XT4IS4D (Paclitaxel) RN - Q6C979R91Y (Vinorelbine) SB - IM MH - Adult MH - Afatinib/adverse effects MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *Breast Neoplasms/drug therapy/genetics MH - Female MH - Humans MH - Lapatinib/therapeutic use MH - Middle Aged MH - Paclitaxel MH - Quinazolines MH - Receptor, ErbB-2/genetics MH - Trastuzumab MH - Treatment Outcome MH - Vinorelbine/therapeutic use PMC - PMC8960620 OTO - NOTNLM OT - Afatinib OT - ErbB OT - HER2 OT - Metastatic breast cancer OT - Resistance COIS- M-CL has received travel and accommodation costs and expenses from Pfizer. C-SH has been involved with advisory councils or committees for Roche, Amgen, Eli Lilly, and Pfizer, received honoraria from Roche, Amgen, Eli Lilly, Pfizer, and Novartis, and received grants or funds from AstraZeneca, Daiichi Sankyo, EirGenix, Eli Lilly, MSD, Novartis, OBI Pharma, Pfizer, and Roche. JT has received honoraria from Amgen, NanoString, Novartis, Pfizer, and Roche and has received consulting fees from NanoString and Pfizer. KP, BS and XJ are current employees of Boehringer Ingelheim. TH, AM, RSA, Y-CC, YY, VV, MJ, and L-MT declare no potential conflict of interest. EDAT- 2022/02/10 06:00 MHDA- 2022/03/31 06:00 PMCR- 2022/02/09 CRDT- 2022/02/09 12:17 PHST- 2021/09/11 00:00 [accepted] PHST- 2022/02/10 06:00 [pubmed] PHST- 2022/03/31 06:00 [medline] PHST- 2022/02/09 12:17 [entrez] PHST- 2022/02/09 00:00 [pmc-release] AID - 10.1007/s10549-021-06449-4 [pii] AID - 6449 [pii] AID - 10.1007/s10549-021-06449-4 [doi] PST - ppublish SO - Breast Cancer Res Treat. 2022 Apr;192(3):593-602. doi: 10.1007/s10549-021-06449-4. Epub 2022 Feb 9.