Abstract 1261P
Background
In approximately 1-3% of all Non-Small Cell Lung Cancers (NSCLC), HER2 mutations are identified as single genomic driver. Despite this prevalence, no targeted treatment against HER2 is currently approved for this subgroup of NSCLC. In the Drug Rediscovery Protocol (DRUP) patients are treated with off-label drugs based on their tumor molecular profile in multiple parallel cohorts. Here, we present the results of the cohort “trastuzumab + pertuzumab for NSCLC with HER2 mutations”.
Methods
Patients (aged ≥ 18 years) with treatment refractory, metastatic or advanced HER2 exon 20 mutated (HER2m+) NSCLC with measurable disease according to RECIST v1.1 were eligible. Treatment with intravenous trastuzumab combined with pertuzumab every 3 weeks was applied until disease progression or unacceptable toxicity. The primary endpoint was clinical benefit (CB: objective response or stable disease (SD) ≥ 16 weeks). Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 patient had CB in stage 1. A fresh frozen biopsy for biomarker analysis, including whole genome sequencing (WGS), was obtained from each patient at baseline.
Results
Twenty-four evaluable patients with HER2m+ NSCLC were treated with trastuzumab + pertuzumab between May 2017 and August 2020. The median number of previous systemic therapy lines was 2 for the included patients. CB was observed in 9 patients (38%), including 2 patients (8%) with partial response (PR) and 7 patients (30%) with SD ≥ 16 weeks. The most frequently observed HER2 mutation was T772_A775dup (71%, n=17). In the current cohort, median follow-up was 13 months, median progression-free survival was 4 months (95% CI 2-6 months), and median overall survival was 9 months (95% CI 4 – not reached). A pre-treatment biopsy was available in 58% of patients and confirmed the inclusion mutation in all cases. No unexpected toxicity was observed.
Conclusions
Trastuzumab + pertuzumab therapy demonstrated a modest overall antitumor activity in pre-treated advanced HER2m+ NSCLC patients, though leading to PR in 2 patients. Additional research is warranted to improve the selection profile.
Clinical trial identification
NCT02925234; Release date: 26 August 2016.
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Clovis Oncology; Eisai; Janssen; Lilly; MSD; Novartis; Pfizer; Roche; Hartwig Medical Foundation; Dutch Cancer Society (KWF); Barcode for Life Foundation (BFL).
Disclosure
J.M. van Berge Henegouwen: Financial Interests, Personal, Invited Speaker: Roche Pharma. A.J. van der Wekken: Financial Interests, Institutional, Advisory Board: Roche Pharma; Financial Interests, Institutional, Research Grant: Scientific Administration. S. Burgers: Financial Interests, Institutional, Advisory Board: Roche Pharma. All other authors have declared no conflicts of interest.