Cancer Res Treat.  2023 Apr;55(2):488-497. 10.4143/crt.2022.359.

Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing

• Ahn BC
• Han YJ
• Kim HR
• Hong MH
• Cho BC
• Lim SM

• KMID: 2541235
• DOI: http://doi.org/10.4143/crt.2022.359

Abstract

Purpose
This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents.
Materials and Methods
Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed.
Results
The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively.
Conclusion
Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

Keyword

mutation; High-throughput nucleotide sequencing; Lung neoplasms; Brain metastasis

Figure

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  Fig. 1 Overall landscape of human epidermal growth factor receptor 2 (HER2) mutation patients detected by next-generation sequencing (n=44).

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  Fig. 2 Kaplan-Meier plot of the median overall survival (mOS) analysis. (A) Overall survival for the entire study population calculated from the date of relapse or metastasis to the last follow-up date. Overall survival of patients stratified by presence of exon 20 mutation (B), treated with pemetrexed-based cytotoxic chemotherapy (C), and human epidermal growth factor receptor 2 (HER2) targeted therapy (Tx) (D). CI, confidence interval; mut, mutation.

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  Fig. 3 Kaplan-Meier plot for the median overall survival (mOS) and median progression-free survival (mPFS) from the beginning of treatment. (A) mOS of patients treated with pemetrexed-based cytotoxic chemotherapy. (B) mPFS with pemetrexed-based cytotoxic chemotherapy. (C) mOS with human epidermal growth factor receptor 2 (HER2) targeted therapy. (D) mPFS with with HER2 targeted therapy. CI, confidence interval; Tx, therapy.

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  Fig. 4 (A) Number of brain metastases when the cancer was first diagnosed. (B) Number of brain metastases that developed during the palliative treatment. (C) Kaplan-Meier plot for the time to brain metastases for patients without initial brain lesions (n=10). The median time to progression was 15.6 months (95% confidence interval [CI], 1.5 to 29.7).

Reference

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