First-Line Therapy in EGFR-Mutated Advanced NSCLC: Survival, High-Risk Disease, and Treatment in the Community Setting

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center opens this CancerNetwork Around the Practice discussion on first-line therapy for epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC) with panelists Matthew Gumbleton, MD, PhD, of Huntsman Cancer Institute, and Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute.

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center walks through the mature overall survival data from the phase 3 MARIPOSA study of amivantamab plus lazertinib in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC).

Matthew Gumbleton, MD, PhD, of Huntsman Cancer Institute and Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute discuss how they translate grade 3 or higher adverse event rates into a conversation a patient can actually use in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC).

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents the final overall survival data from the phase 3 FLAURA2 study of osimertinib plus chemotherapy in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), at more than 47.5 months versus approximately 38 months for osimertinib alone, and asks how the panel handles cross-trial comparison.

Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute pushes back on the high-risk label in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), noting that when 89% of patients with analyzable circulating tumor DNA in the phase 3 MARIPOSA study carry at least 1 high-risk feature, the term loses meaning.

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center contrasts central nervous system (CNS) imaging in the phase 3 MARIPOSA and FLAURA2 studies of epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), noting that one scanned every patient on a set schedule while the other continued imaging mainly in patients with baseline brain metastases.

Matthew Gumbleton, MD, PhD, of Huntsman Cancer Institute rejects the idea that a TP53 co-mutation points toward chemotherapy in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC).

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center describes COPERNICUS, a pragmatic study of first-line subcutaneous amivantamab plus lazertinib with protocol-directed supportive care in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), which was open at her own site.

Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute says he sees no remaining role for intravenous amivantamab in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), with subcutaneous administration taking 10 to 15 minutes and easing chair time and scheduling.

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents long-term resistance data from the phase 3 MARIPOSA study in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), where amivantamab plus lazertinib reduced acquired MET amplification approximately fourfold and secondary EGFR resistance mutations approximately fivefold compared with osimertinib.

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents a 68-year-old woman with newly diagnosed metastatic lung adenocarcinoma, an epidermal growth factor receptor (EGFR) exon 19 deletion with a concurrent TP53 co-mutation, multiple small asymptomatic brain metastases on staging magnetic resonance imaging, disease confined to lung and brain, and good performance status with support at home.

Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute says he tries not to push patients with asymptomatic brain metastases from epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC) toward local therapy, calling whole brain radiation the wrong step for this patient and noting that another consultation costs the patient time.

Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents a 74-year-old woman with epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC), no central nervous system involvement, limited mobility, osteoporosis and rheumatoid arthritis, who lives alone an hour from the cancer center and depends on others for transportation.

Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute describes what it takes to deliver combination therapy for epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC) outside a trial, crediting financial advocates, social workers, nurses and pharmacists.