Scholarlink

Introduction <p>Data regarding the comparative efficacy of various generations of tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC) in lower middle-income countries (LMICs) is scarce.</p> Methods <p>A comprehensive assessment of anaplastic lymphoma kinase (ALK)-directed TKIs and treatment sequences was done for 249 patients (145 male, 104 female) with advanced NSCLC at a referral cancer hospital in New Delhi, India. The primary endpoints were overall survival (OS); progression-free survival on 1st-line (PFS1) therapy, 2nd-line (PFS2) therapy, and PFS1 + 2. Multivariable Cox proportional hazards and joint frailty modelling were used for progression events and OS, respectively.</p> Results <p>With a median follow-up of 48&#xa0;months, median OS, PFS1, and PFS1 + 2 were 46.6 (95%&#xa0;CI 36.9–67.0), 18.2 (95%&#xa0;CI 14.5–26.8), and 33.1&#xa0;months (95%&#xa0;CI 28.6–41.6), respectively. Third-generation TKIs significantly improved PFS and OS over 1st-generation TKIs, whether used 1st-line or later (HR PFS1 0.08, 95%&#xa0;CI 0.02–0.32, <i>p</i> &lt; 0.001; HR OS 0.13, 95%&#xa0;CI 0.02–0.94, <i>p</i> = 0.043; HR PFS2 0.36, 95%&#xa0;CI 0.19–0.71, <i>p</i> = 0.003). Joint frailty modelling confirmed the correlation between repeated progression events and mortality (shared frailty parameter theta = 1.78, <i>p</i> &lt; 0.001). Alectinib (HR 0.53, 95%&#xa0;CI 0.33–0.84, <i>p</i> = 0.007) and lorlatinib (HR 0.49, 95%&#xa0;CI 0.31–0.77, <i>p</i> = 0.002) reduced progression risk. Temporal trend analyses showed fewer treatment lines and significantly improved outcomes in patients with brain metastases with 3rd-generation TKIs.</p> Conclusions <p>This relatively large LMIC real-world study shows similar outcomes to Western data, and improved survival and lower risk of intracranial progression with 2nd- and 3rd-generation ALK-directed TKIs.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A Decade of Treating ALK-Rearranged Non-Small Cell Lung Cancer in a Lower Middle-Income Country: Changing Patterns and Improving Survival

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月17日

查看全文
  • Ullas Batra,
  • Mansi Sharma,
  • Irfan Ahmad,
  • Senthil Rajappa,
  • Shrinidhi Nathany,
  • Luca Cantini,
  • Rashi Sachdeva,
  • Vanshika Batra,
  • Ritwika Choudhury,
  • Bhumi Agarwal,
  • Abhinav Dewan,
  • Sabeena Choudhary,
  • B. P. Amrith,
  • L. M. Darlong,
  • Kundan Singh Chufal,
  • Preetha Umesh,
  • Kratika Bhatia,
  • Paulo Nunes Filho,
  • Kamal S. Saini,
  • Anurag Mehta

摘要

Introduction

Data regarding the comparative efficacy of various generations of tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC) in lower middle-income countries (LMICs) is scarce.

Methods

A comprehensive assessment of anaplastic lymphoma kinase (ALK)-directed TKIs and treatment sequences was done for 249 patients (145 male, 104 female) with advanced NSCLC at a referral cancer hospital in New Delhi, India. The primary endpoints were overall survival (OS); progression-free survival on 1st-line (PFS1) therapy, 2nd-line (PFS2) therapy, and PFS1 + 2. Multivariable Cox proportional hazards and joint frailty modelling were used for progression events and OS, respectively.

Results

With a median follow-up of 48 months, median OS, PFS1, and PFS1 + 2 were 46.6 (95% CI 36.9–67.0), 18.2 (95% CI 14.5–26.8), and 33.1 months (95% CI 28.6–41.6), respectively. Third-generation TKIs significantly improved PFS and OS over 1st-generation TKIs, whether used 1st-line or later (HR PFS1 0.08, 95% CI 0.02–0.32, p < 0.001; HR OS 0.13, 95% CI 0.02–0.94, p = 0.043; HR PFS2 0.36, 95% CI 0.19–0.71, p = 0.003). Joint frailty modelling confirmed the correlation between repeated progression events and mortality (shared frailty parameter theta = 1.78, p < 0.001). Alectinib (HR 0.53, 95% CI 0.33–0.84, p = 0.007) and lorlatinib (HR 0.49, 95% CI 0.31–0.77, p = 0.002) reduced progression risk. Temporal trend analyses showed fewer treatment lines and significantly improved outcomes in patients with brain metastases with 3rd-generation TKIs.

Conclusions

This relatively large LMIC real-world study shows similar outcomes to Western data, and improved survival and lower risk of intracranial progression with 2nd- and 3rd-generation ALK-directed TKIs.