Molecular testing, treatment patterns, and outcomes in EGFR-mutated non-small cell lung cancer: the PISCES study

Panwen Tian1,2, Lin Wu3, Chengzhi Zhou4

  • 1Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Center/Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract

Insights

Molecular testing after first-line epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy is crucial. T790M-positive patients receiving third-generation EGFR-TKIs showed improved outcomes in China.

Area of Science:

  • Oncology
  • Molecular Biology
  • Clinical Research

Background:

  • Limited real-world data exists on treatment patterns and prognosis for Chinese patients progressing after first-line epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy.
  • This study addresses the gap by investigating molecular testing, treatment strategies, and outcomes in this patient population.

Purpose of the Study:

  • To evaluate second-line (2L) treatment patterns and clinical outcomes in Chinese patients who progressed on first-line (1L) EGFR-TKIs.
  • To assess the impact of molecular testing, specifically T790M mutation status, on treatment selection and patient prognosis.

Main Methods:

  • Prospective enrollment of eligible patients across 16 centers in China.
  • Collection of data on 2L treatment patterns, molecular testing (tissue and plasma), and clinical outcomes, including median progression-free survival (mPFS) and median overall survival (mOS).

Main Results:

  • Of 291 patients, 213 underwent molecular testing; T790M mutations were detected in 53.8% (tissue) and 43.7% (plasma).
  • T790M-positive patients receiving third-generation (3G) EGFR-TKIs as 2L therapy achieved mPFS of 14.7 months and mOS of 32.0 months.
  • T790M-negative patients receiving 3G EGFR-TKIs, prior EGFR-TKIs plus local therapy, or chemotherapy had mPFS ranging from 4.9 to 10.2 months and mOS from 15.0 to 21.2 months.

Conclusions:

  • Molecular testing following acquired resistance to first-generation (1G)/second-generation (2G) EGFR-TKIs is valuable.
  • Third-generation (3G) EGFR-TKIs demonstrate superior clinical outcomes, particularly in T790M-positive patients, highlighting the importance of targeted therapy guided by molecular profiling.