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

Area of Science:

• Oncology
• Pharmacology
• Clinical Research

Background:

• Limited data exists on the comparative efficacy of different generations of tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) in lower middle-income countries (LMICs).
• Real-world data from LMICs is crucial for understanding treatment effectiveness in diverse populations.

Purpose of the Study:

• To evaluate the efficacy of anaplastic lymphoma kinase (ALK)-directed TKIs in advanced NSCLC patients in an LMIC setting.
• To compare outcomes across different generations of TKIs and treatment sequences.
• To assess the impact of TKIs on overall survival (OS) and progression-free survival (PFS).

Main Methods:

• A cohort of 249 advanced NSCLC patients treated at a referral cancer hospital in New Delhi, India, was analyzed.
• Primary endpoints included overall survival (OS), first-line PFS (PFS1), second-line PFS (PFS2), and combined PFS1+2.
• Statistical analyses employed multivariable Cox proportional hazards and joint frailty modeling.

Main Results:

• Median OS was 46.6 months, PFS1 was 18.2 months, and PFS1+2 was 33.1 months.
• Third-generation TKIs demonstrated significant improvements in PFS and OS compared to first-generation TKIs.
• Alectinib and lorlatinib showed reduced progression risk, and third-generation TKIs improved outcomes for patients with brain metastases.

Conclusions:

• Real-world data from this LMIC study aligns with Western findings for ALK-directed TKIs in NSCLC.
• Second- and third-generation ALK-directed TKIs significantly improve survival and reduce intracranial progression.
• These findings support the use of newer generation TKIs in NSCLC treatment within LMIC settings.