Dr Florez on First-Line Treatment Factors in EGFR+ NSCLC

“The [right] answer depends on the patterns for oligoprogression. I think local therapy continues to be an important part of the treatment for [EGFR-mutated NSCLC].”

Narjust Florez, MD, the associate medical director of the Cancer Care Access Program and a thoracic medical oncologist at the Dana-Farber Brigham Cancer Center, a member of faculty at Harvard Medical School, and co-chair of the 2025 Bridging the Gaps in Lung Cancer Meeting, discussed evolving treatment considerations for patients with EGFR-mutated non–small cell lung cancer (NSCLC) during a live-streamed audience polling session.

In response to the question of which factor most influences first-line treatment selection for patients with metastatic NSCLC harboring EGFR mutations, the majority of participants cited overall survival (OS) benefit, followed by patient preference. Florez noted that this discussion is particularly timely given recent data from the phase 3 MARIPOSA trial (NCT04487080), which demonstrated that amivantamab-vmjw (Rybrevant) plus lazertinib (Leclaza) significantly improved OS compared with osimertinib (Tagrisso) monotherapy. In parallel, a July 2025 news release revealed a positive OS outcome from the phase 3 FLAURA2 trial (NCT04035486) evaluating osimertinib in combination with platinum-based chemotherapy, although full data have not yet been publicly published or presented.

Florez emphasized that although OS remains the most critical determinant in therapeutic decision-making, the patient experience and treatment burden must also be considered. Both MARIPOSA and FLAURA2 regimens are associated with increased toxicity and treatment complexity relative to daily oral osimertinib alone, highlighting the need for shared decision-making.

The session also addressed clinical approaches to progression on an EGFR TKI, particularly the role of continuing EGFR inhibition beyond progression. For these patients, approximately 49% to 57% of poll respondents favored ongoing EGFR TKI therapy select situations. Florez confirmed this as current standard practice, noting continued EGFR-targeted therapy in conjunction with localized treatment could extend disease control after progression in select patients with oligoprogression.

In cases of systemic progression, the decision to continue EGFR inhibition depends on subsequent therapy. For example, amivantamab, a bispecific EGFR/MET bispecific antibody, provides EGFR blockade and does not require osimertinib co-administration. Similarly, datopotamab deruxtecan (Dato-DXd; Datroway), an antibody-drug conjugate targeting TROP2, may be used post-progression without concurrent EGFR inhibition.