Amivantamab/Lazertinib Shows 41-Month Survival in Atypical EGFR NSCLC: What Nurses Need to Know

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, updated results from the CHRYSALIS-2 study revealed a clinically meaningful median overall survival (OS) of approximately 3.5 years for patients with atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC) treated with first-line amivantamab (Rybrevant) and Lazertinib (Lacluze).

Joel Neal, MD, PhD, a thoracic oncology specialist and Professor of Medicine at Stanford Health Care, presented the findings, which address a significant unmet need for patients harboring less frequent mutations such as G719X, S768I, and L861Q.

Atypical mutations account for roughly 5% to 10% of EGFR-mutated NSCLC cases. Historically, these patients have had fewer effective options, as traditional tyrosine kinase inhibitors (TKIs) often demonstrate shorter durations of response in this population compared to common mutations. In CHRYSALIS-2 Cohort C, treatment-naïve patients achieved a median OS of 41.0 months with the amivantamab-lazertinib combination. This outcome stands in contrast to a real-world cohort receiving physician-selected first-line TKIs, which showed a median OS of 15.2 months.

The combination therapy utilizes amivantamab, a bispecific antibody providing dual EGFR and MET inhibition with immune-cell directing activity, alongside lazertinib, a third-generation EGFR TKI. The efficacy data was robust, with an overall response rate (ORR) of 57% and a clinical benefit rate (CBR) of 84%. These responses were durable, with a median duration of response reaching 20.7 months.

For the oncology nursing community, the study’s safety profile underscores the necessity of proactive symptom management. Common treatment-emergent adverse events (AEs) included paronychia (78%), rash (65%), hypoalbuminemia (61%), and stomatitis (35%). MET-inhibition-related AEs, such as peripheral edema (41%), were also observed. Additionally, because CHRYSALIS-2 utilized the intravenous (IV) formulation of amivantamab, infusion-related reactions (IRRs) occurred in 61% of participants.

Neal pointed out that while toxicities were manageable, they require diligent oversight to maintain treatment adherence. Preemptive strategies can significantly lower the incidence of severe rashes. He recommended the liberal use of skin emollients and moisturizers and oral antibiotics to prevent the skin rash and prevent colonization of organisms that cause pustular eruptions.

Looking forward, Neal noted that more recent studies using enhanced supportive care protocols and subcutaneous amivantamab have shown even lower rates of AEs and IRRs than those seen in the earlier phases of CHRYSALIS-2.