Sandip P. Patel, MD; Zofia Piotrowska, MD, MHS; and Joel Neal, MD, PhD, discuss how the evolving landscape of EGFR-mutated non–small cell lung cancer treatment now includes 3 compelling frontline options (osimertinib monotherapy, FLAURA2 regimen, and MARIPOSA), requiring careful consideration of patient factors, disease characteristics, and toxicity profiles for optimal treatment selection and sequencing strategies.
Panelists discuss how FLAURA2 regimen (osimertinib plus chemotherapy) is being incorporated into frontline EGFR-mutated NSCLC treatment, with considerations for escalating to combination therapy based on disease burden, CNS metastases, and patient tolerance factors.
Panelists discuss how the MARIPOSA regimen (amivantamab plus lazertinib) shows promising overall survival benefits in first-line treatment, though with increased toxicity concerns including rash, edema, and VTE risk requiring careful patient selection.
Panelists discuss how CNS metastases in EGFR-mutated NSCLC require multidisciplinary management with close radiation oncology collaboration, frequent monitoring, and preference for FLAURA2 regimen due to superior intracranial efficacy data.
Panelists discuss how oligometastatic disease treatment requires careful definition of metastatic burden, with liver metastases potentially indicating more aggressive biology and warranting consideration of intensified frontline therapy.
Panelists discuss how balancing safety and efficacy in frontline regimens involves managing distinct toxicity profiles, with FLAURA2 requiring standard chemotherapy monitoring vs MARIPOSA necessitating complex supportive care for EGFR-related skin toxicity and venous thromboembolism prophylaxis.
Panelists discuss how second-line treatment selection depends heavily on frontline therapy choice, emphasizing the importance of repeat biopsies to identify resistance mechanisms and considering continuation of TKI with added chemotherapy for patients with controlled CNS disease.
Panelists discuss how HER3-directed ADC patritumab deruxtecan shows promise as a later-line therapy with approximately 30% response rates and intracranial activity, though biomarker selection remains elusive and mechanism of CNS penetration unclear.
Panelists discuss how TROP2-targeted ADC dato-DXd represents another promising option with evolving digital pathology biomarker approaches, though practical implementation and patient selection strategies remain challenging.
Panelists discuss how ADC-based therapies like dato-DXd offer superior efficacy compared with traditional chemotherapy options like docetaxel, while requiring careful monitoring for unique toxicities including ILD, stomatitis, and ocular effects.
Panelists discuss how future developments in EGFR-mutated non–small cell lung cancer (NSCLC) will focus on biomarker-driven patient selection, rational sequencing strategies, and emerging therapies including cellular therapy and treatments for atypical EGFR mutations.
