WCLC 2025 - Posters & ePosters-EP.12.56 Ipd Meta-Analysis of Intracranial Efficacy: Can CNS Data Refine First-Line Choices in EGFR-Mutant NSCLC?

Pdf Summary

This study presents an individual patient data (IPD) meta-analysis evaluating intracranial (CNS) efficacy of two frontline EGFR-targeted regimens in EGFR-mutant non-small cell lung cancer (NSCLC): amivantamab plus lazertinib (AMILAZ) and osimertinib plus chemotherapy (OSICT). CNS progression remains a significant clinical challenge in these patients. The analysis pooled data from 705 patients across the MARIPOSA (AMILAZ) and FLAURA2 (OSICT) trials, including 188 patients with brain metastases at baseline.<br /><br />Key intracranial outcomes assessed were intracranial progression-free survival (iPFS), intracranial objective response rate (iORR), CNS complete response (CR), and time to CNS progression. Statistical models adjusted for baseline CNS involvement and trial effects.<br /><br />Among patients with baseline brain metastases, median iPFS was similar between AMILAZ (17.6 months) and OSICT (18.2 months), with 12-month iPFS rates around 71-74%. Intracranial objective response rates were also comparable (~60%), while CNS complete response rates were numerically lower with AMILAZ (31%) versus OSICT (43%), though not statistically significant. In patients without baseline brain metastases, there was a numerical trend towards lower incidence of new CNS metastases at 18 months with AMILAZ (10.2%) compared to OSICT (14.6%), but this difference did not reach statistical significance.<br /><br />Overall, the data indicate that AMILAZ offers intracranial efficacy comparable to OSICT in patients with existing brain metastases and may have a favorable impact on CNS progression prevention in those without baseline CNS disease. These findings support the use of AMILAZ as an effective CNS-active first-line treatment option for EGFR-mutant NSCLC. The study also emphasizes the importance of incorporating dedicated CNS-specific endpoints in future trials to better guide first-line treatment decisions in this population.

Asset Subtitle

Blerina Resuli

Meta Tag

Speaker Blerina Resuli

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR-mutant non-small cell lung cancer

intracranial efficacy

central nervous system progression

amivantamab plus lazertinib

osimertinib plus chemotherapy

brain metastases

intracranial progression-free survival

intracranial objective response rate

CNS complete response

first-line treatment