Dr Halmos on Treatment Strategies For EGFR-Mutant NSCLC

Balazs Halmos, MD, professor, Department of Oncology (Medical Oncology), professor, Department of Medicine (Oncology & Hematology), associate director, Clinical Science, Montefiore Einstein Comprehensive Cancer Center, discusses treatment strategies for patients with EGFR-mutant non–small cell lung cancer (NSCLC).

Both the phase 3 FLAURA2 (NCT04035486) and MARIPOSA (NCT04487080) trials are important EGFR-mutant NSCLC studies that reached their primary end points of prolonged median progression-free survival (PFS), Halmos says. In FLAURA2, treatment with osimertinib (Tagrisso) plus chemotherapy led to a median PFS of 25.5 months (95% CI, 24.7-not calculable [NC]) months vs 16.7 months (95% CI, 14.1-21.3) with osimertinib monotherapy (HR 0.62; 95% CI, 0.49-0.79; P < .001). Although the PFS benefit with the combination appears to be clinically meaningful, this approach is associated with several added toxicities from conventional chemotherapy—especially during the first 3 months of therapy, Halmos explains. Furthermore, the overall survival (OS) benefit achieved with osimertinib plus chemotherapy over osimertinib alone is currently unknown, and therefore, EGFR-targeted regimens need to be introduced to the NSCLC treatment paradigm with caution, Halmos notes.

However, patients with NSCLC and baseline brain metastases, who typically have poor prognoses, appear to benefit from osimertinib plus chemotherapy more than other subgroups, with a median PFS of 24.9 months (95% CI, 22.0-NC; HR, 0.47; 95% CI, 0.33-0.66), according to Halmos. These data support the consideration of osimertinib plus chemotherapy for the treatment of patients with brain metastases, Halmos adds.

The MARIPOSA trial, which evaluated the bispecific antibody lazertinib plus the EGFR-MET inhibitor amivantamab (Rybrevant) in patients with EGFR-mutant NSCLC, demonstrated a median PFS of 23.7 months (95% CI, 19.1-27.7) with the investigational regimen vs 16.6 months (95% CI, 14.8-18.5) with osimertinib (HR, 0.70; 95% CI, 0.58-0.85; P < .001). Similarly to FLAURA2, although the MARIPOSA efficacy findings were impressive, several adverse effects (AEs) are associated with this regimen, including skin and gastrointestinal toxicities as well as infusion reactions and a high rate of thromboembolic effects, Halmos emphasizes. To date, no specific patient subgroup appears to derive more benefit than others with the MARIPOSA regimen, Halmos says. However, lazertinib plus amivantamab has demonstrated an early trend toward an OS advantage, which may become significant over time and further support the use of this regimen in patients with EGFR-mutated NSCLC, Halmos explains.

AE mitigation strategies are necessary for the safe and successful integration of the FLAURA2 and MARIPOSA regimens into clinical practice, according to Halmos. One such strategy is the potential development of subcutaneous versions of these agents, Halmos concludes.