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Trastuzumab and pertuzumab combination therapy for advanced pre-treated HER2 exon 20-mutated non-small cell lung cancer.
van Berge Henegouwen, J M; Jebbink, M; Hoes, L R; van der Wijngaart, H; Zeverijn, L J; van der Velden, D L; Roepman, P; de Leng, W W J; Jansen, A M L; van Werkhoven, E; van der Noort, V; van der Wekken, A J; de Langen, A J; Voest, E E; Verheul, H M W; Smit, E F; Gelderblom, H.
Afiliación
  • van Berge Henegouwen JM; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; Oncode Institute, the Netherlands.
  • Jebbink M; Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Hoes LR; Oncode Institute, the Netherlands; Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • van der Wijngaart H; Oncode Institute, the Netherlands; Department of Medical Oncology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
  • Zeverijn LJ; Oncode Institute, the Netherlands; Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • van der Velden DL; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.
  • Roepman P; Hartwig Medical Foundation, Amsterdam, the Netherlands.
  • de Leng WWJ; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Jansen AML; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • van Werkhoven E; Biometrics Department, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • van der Noort V; Biometrics Department, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • van der Wekken AJ; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • de Langen AJ; Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Voest EE; Oncode Institute, the Netherlands; Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Verheul HMW; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Smit EF; Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
  • Gelderblom H; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: a.j.gelderblom@lumc.nl.
Eur J Cancer ; 171: 114-123, 2022 08.
Article en En | MEDLINE | ID: mdl-35716537
INTRODUCTION: In 1-3% of non-small cell lung cancer (NSCLC) human epidermal growth factor 2 (HER2) mutations are identified as a genomic driver. Nevertheless, no HER2-targeted treatment is approved for NSCLC. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile. Here, we present the results of the cohort 'trastuzumab/pertuzumab for HER2 exon20 mutation positive (HER2m+) NSCLC'. METHODS: Patients with treatment refractory, advanced HER2m+ NSCLC with measurable disease (RECISTv1.1) were eligible. Treatment with intravenous trastuzumab combined with pertuzumab every 3 weeks was administered. The primary end-point was clinical benefit (CB: either objective response or stable disease ≥ 16 weeks). Patients were enrolled using a Simon-like 2-stage design, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 patient had CB in stage 1. At baseline, a biopsy for biomarker analysis, including whole genome sequencing, was obtained. RESULTS: Twenty-four evaluable patients were enrolled and treated between May 2017 and August 2020. CB was observed in 9 patients (38%); including an objective response rate of 8.3% (2 patients had a partial response) and 7 patients with stable disease ≥ 16 weeks. The most frequently observed HER2 mutation was p.Y772_A775dup (71%, n = 20). Median follow-up was 13 months, median progression-free survival and overall survival 4 (95% CI 3-6) and 10 months (95% CI 4 - not reached), respectively. Whole genome sequencing data (available for 67% of patients) confirmed the inclusion mutation in all cases. No unexpected toxicity was observed. CONCLUSION: Despite the fact that the study did meet its primary end-point, trastuzumab/pertuzumab was only marginally active in a subset of patients with heavily pre-treated HER2m+ NSCLC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Guideline / Prognostic_studies Límite: Female / Humans Idioma: En Revista: Eur J Cancer Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Guideline / Prognostic_studies Límite: Female / Humans Idioma: En Revista: Eur J Cancer Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido