Trastuzumab and pertuzumab combination therapy for advanced pre-treated HER2 exon 20-mutated non-small cell lung cancer.

Abstract

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.

• Authors: J M van Berge Henegouwen, M Jebbink, L R Hoes, H van der Wijngaart, L J Zeverijn, D L van der Velden, P Roepman, W W J de Leng, A M L Jansen, E van Werkhoven, V van der Noort, A J van der Wekken, A J de Langen, E E Voest, H M W Verheul, E F Smit, H Gelderblom
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 171 Pg. 114-123 (08 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 35716537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Receptor, ErbB-2
• pertuzumab
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Exons
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Receptor, ErbB-2 (metabolism)
• Trastuzumab (therapeutic use)