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Outcomes of Pemetrexed-based chemotherapies in HER2-mutant lung cancers

Yan Wang1, Shijia Zhang1,2, Fengying Wu1

  • 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, No. 507 Zheng Min Road, Shanghai, 200433, People's Republic of China.

BMC Cancer
|March 29, 2018
PubMed
Abstract

Insights

First-line chemotherapy with pemetrexed showed limited efficacy in advanced HER2-mutant non-small cell lung cancer (NSCLC). Patients with HER2 mutations experienced shorter progression-free survival compared to those with ALK/ROS1 rearrangements, highlighting the need for targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Pulmonology

Background:

  • HER2 mutations are oncogenic drivers in non-small cell lung cancer (NSCLC).
  • HER2-targeted therapies show promise, but chemotherapy outcomes in HER2-mutant NSCLC are understudied.
  • This study investigates chemotherapy efficacy in advanced HER2-mutant lung adenocarcinomas.

Purpose of the Study:

  • To evaluate the efficacy of first-line pemetrexed-based chemotherapy in advanced HER2-mutant lung adenocarcinomas.
  • To compare treatment outcomes between HER2-mutant and other driver-mutant NSCLC groups (EGFR, KRAS, ALK/ROS1).

Main Methods:

  • 1714 advanced NSCLC patients were tested for common mutations (EGFR, KRAS, BRAF) and rearrangements (ALK, ROS1).
  • HER2 mutations were assessed in mutation-negative cases using amplification refractory mutation system (ARMS).
  • Efficacy of first-line pemetrexed-based chemotherapy was analyzed in HER2-mutant, EGFR-mutant, ALK/ROS1-rearranged, and KRAS-mutant groups.

Main Results:

  • HER2 mutations were found in 5.1% of selected NSCLC patients (29/572), all adenocarcinomas.
  • In HER2-mutant patients receiving pemetrexed (n=25), objective response rate was 36.0% and median progression-free survival (PFS) was 5.1 months.
  • PFS was similar to KRAS-mutant (5.0 months), shorter than EGFR-mutant (6.5 months), and significantly shorter than ALK/ROS1-rearranged (9.2 months) groups.

Conclusions:

  • Advanced HER2-mutant lung adenocarcinomas have inferior outcomes with first-line pemetrexed-based chemotherapy compared to ALK/ROS1-rearranged NSCLC.
  • These findings underscore the urgent need for effective HER2-targeted therapies in clinical practice.
Keywords:
HER2 mutationLung adenocarcinomaPemetrexed

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