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New Options Challenge Standard Treatments in EGFR-Mutant NSCLC (MARIPOSA and MARIPOSA-2 Trials)

*October 2023*

Take home message: In 1L setting, combo of Amivantamab (ami), an EGFR-MET bispecific antibody, and Lazertinib (laz), a CNS-penetrant 3rd-generation EGFR TKI, was evaluated against Osimertinib (osi) in the MARIPOSA study (NCT04487080) for treatment-naïve, EGFR-mutated locally advanced or metastatic NSCLC. After a median follow-up of 22.0 months, ami+laz demonstrated a significant 30% reduction in the risk of disease progression or death compared to osi, with a median PFS of 23.7 months, along with a favorable trend in OS. The combination also showed a higher duration of response (DoR) and similar safety profiles, establishing ami+laz as a new first-line standard of care for EGFR-mutated advanced NSCLC.

Combo Amivantamab with chemotherapy and Amivantamab with lazertinib and chemotherapy improved progression-free survival and intracranial progression-free survival in patients with EGFR-mutated advanced non-small cell lung cancer following osimertinib progression, with notable hematologic, EGFR, and MET-related adverse events. (From OncoAlert)

MADRID — Two positive phase III trials involving amivantamab (Rybrevant)-based regimens introduced new first- and second-line options in EGFR-mutant non-small cell lung cancer (NSCLC), though toxicity with the combination strategies raised some concerns.

In the first-line trial, treatment with the targeted combination of amivantamab plus lazertinib significantly improved median progression-free survival (PFS) by about 7 months over the current standard, single-agent osimertinib (Tagrisso). Early overall survival (OS) assessment showed no significant difference between arms, but Kaplan-Meier curves started to separate in favor of the combination, reported Byoung Chul Cho, MD, PhD, of Yonsei Cancer Center in Seoul, Korea.

And in a study involving patients who had already progressed on osimertinib, adding either amivantamab alone or amivantamab-lazertinib to a standard second-line chemotherapy regimen improved median PFS by about 2 to 4 months, while nearly doubling response rates versus chemotherapy alone. The two investigational strategies improved intracranial PFS as well, though interim OS data showed no significant difference compared with chemotherapy alone, according to findings presented by Antonio Passaro, MD, PhD, of the European Institute of Oncology, IRCCS in Milan.

Increased toxicity showed up in all of the investigational arms — including more dermatologic toxicities, infusion-related reactions, and venous thromboembolism (VTE) with amivantamab-lazertinib in particular — a potential concern especially in the upfront setting where patients could stay on treatment for years.

Findings from the two trials, MARIPOSA and MARIPOSA-2, were presented here during a late-breaking session at the European Society for Medical Oncology (ESMO)opens in a new tab or window congress, and challenge the current treatment landscape in locally advanced unresectable and metastatic EGFR-mutant NSCLC. Read more.