Dr. Jonathan Riess introduces the program on first-line treatment strategies in EGFR-mutated NSCLC, joined by Dr. Mary Jo Fidler and Dr. Matthew Gumbleton.
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First-Line Treatment Strategies in EGFR-Mutated NSCLC: Managing Toxicity and Supporting Treatment Continuity
Dr. Jonathan Riess from UC Davis Comprehensive Cancer Center moderated a discussion with Dr. Mary Jo Fidler from Rush University Medical Center and Dr. Matthew Gumbleton from Huntsman Cancer Institute on first-line treatment selection and proactive toxicity management for patients with EGFR-mutated non-small cell lung cancer (NSCLC). With two combination regimens now demonstrating overall survival benefit over osimertinib monotherapy, including amivantamab-lazertinib (MARIPOSA) and osimertinib plus carboplatin-pemetrexed (FLAURA2), the discussion addresses how to individualize frontline EGFR-mutated NSCLC treatment selection based on TP53 co-mutation status, CNS metastases, and patient-specific factors. The COCOON dermatologic prophylaxis protocol, COPERNICUS study design, subcutaneous amivantamab, dose modification strategies, and patient education frameworks are covered in depth. Two clinical scenarios illustrate shared decision-making for a never-smoking woman with TP53 co-mutation and a patient with CNS metastases, with closing practice pearls emphasizing frontline treatment intensification for the majority of patients with EGFR-mutated advanced NSCLC.
First-Line Treatment Strategies in EGFR-Mutated NSCLC: Managing Toxicity and Supporting Treatment Continuity
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Dr. Riess highlights TP53 co-mutation as one of the most compelling high-risk subgroups in EGFR-mutated NSCLC, asking Dr. Fidler how TP53 co-mutation status influences frontline treatment selection.
Dr. Riess addresses the high rate of CNS metastasis development in EGFR-mutated NSCLC (25%-45%), noting that MARIPOSA's requirement for serial brain MRIs in all participants generated robust intracranial efficacy data.
Dr. Gumbleton explains the mechanism of action of amivantamab-lazertinib for clinicians treating patients with EGFR-mutated NSCLC.
Dr. Riess presents the COCOON trial data, which evaluated a standardized prophylactic regimen for dermatologic adverse event management with amivantamab-lazertinib in patients with EGFR-mutated NSCLC.
Dr. Gumbleton discusses how proactive dermatologic management translates into day-to-day clinical practice for patients receiving amivantamab-lazertinib for EGFR-mutated NSCLC.
EP. 7: Dose Modifications, Subcutaneous Amivantamab, and Monitoring Strategies in EGFR-Mutated NSCLC
Dr. Riess addresses dose modification frequency in MARIPOSA: dose interruptions in 83% of patients, dose reductions in 59%, and any-agent discontinuation in 35%, with only 10% discontinuing all agents due to treatment-related adverse events.
Dr. Riess presents a 52-year-old never-smoking woman with stage IV EGFR exon 19 deletion non-small cell lung cancer, performance status 0, full-time employment as a teacher, no significant comorbidities, and no baseline CNS metastases on brain MRI.
Dr. Riess presents a 55-year-old male former light smoker with stage IV EGFR L858R adenocarcinoma, ECOG performance status 1, three small asymptomatic brain metastases (largest 8 mm) on baseline brain MRI, no TP53 or other high-risk co-mutation, employed as a remote software engineer with concern about preserving cognitive function and work capacity.
Dr. Gumbleton's primary practice pearl for the management of patients with EGFR-mutated NSCLC in 2026: with very few exceptions, every treatment-naïve patient deserves frontline combination therapy.
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