Dr Felip on Treating EGFR-Mutated NSCLC and Supporting Trial Data

“We need to test and analyze if patients [with EGFR-mutated NSCLC] have brain metastases at baseline”

Enriqueta Felip, MD, PhD, a professor of medicine at Universitat de Vic, as well as the head of the Thoracic and Head and Neck Cancer Unit at Vall d’Hebron Hospital, discussed treatment approaches in EGFR-mutated non–small cell lung cancer (NSCLC), including relevant clinical trial data and next steps for the space considering new National Comprehensive Cancer Network (NCCN) guidelines.

Felip began by outlining her approach to treating patients with EGFR-mutated NSCLC, emphasizing the need for standardized baseline testing for brain metastases. Felip underscored the need for baseline brain metastases testing by highlighting data from the phase 3 FLAURA 2 (NCT04035486) and MARIPOSA (NCT04487080) trials, data from which respectively supported the FDA approvals of amivantamab (Rybrevant) plus lazertinib (Lazcluze) in August 2024 and osimertinib (Tagrisso) plus chemotherapy in February 2024.

Felip noted that a high percentage of the patients in FLAURA-2 and MARIPOSA were reported to have brain metastases at the start of each study. Moreover, regarding the efficacy data that showed improvements with combination therapies from each trial, Felip added that she believes combination therapies should be the standard of care in the space.

In MARIPOSA, the combination of amivantamab plus lazertinib reduced the risk of progression or death in patients with EGFR-mutated NSCLC by 30% (HR, 0.70; 95% CI, 0.58-0.85; P < .001) compared with osimertinib alone. Furthermore, in FLAURA 2, patients with EGFR-mutated NSCLC who were treated with osimertinib plus chemotherapy (n = 279) experienced a median progression-free survival of 25.5 months (95% CI, 24.7-not evaluable) vs 16.7 months (95% CI, 14.1-21.3) in those treated with osimertinib alone (n = 278; HR, 0.62; 95% CI, 0.49-0.79; 2-sided P <.0001).

Felip then explored considering local treatments for brain metastases before starting combination therapies. She stated that more data on this topic are needed for a clear answer, also noting that NCCN guidelines allow patients to start combination therapies if they show no symptoms. Pivoting to NCCN guidelines for patients with EGFR-mutated NSCLC and CNS metastases entirely, Felip said that they too recommend systemic and combination therapies. She concluded by touching on how she believes that NCCN guidelines will be updated after more trial data releases.