In a Phase III study known as LASER301 (NCT04248829) and published in the Journal of Clinical Oncology, lazertinib (formerly YH25448), a third-generation EGFR TKI, demonstrated significant efficacy improvement compared to gefitinib (Iressa) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) when used as a first-line treatment.
At the data cutoff on July 29, 2022, the study findings revealed that patients who received lazertinib (n=196) experienced a median progression-free survival (PFS) of 20.6 months, whereas those treated with gefitinib (n=197) had a median PFS of 9.7 months. The overall response rates (ORR) were similar between the two groups. The PFS benefit of lazertinib over gefitinib was consistent across various subgroups, including patients with different performance statuses, age groups, and ethnicities.
The median duration of response (DOR) was longer in the lazertinib group compared to the gefitinib group. The disease control rates (DCRs) were similar in both arms. As for overall survival (OS), data were still immature at the time of the data cutoff, but there was a trend suggesting a potential survival benefit with lazertinib.
Both groups of patients received subsequent therapies after discontinuing the initial treatment, with more patients in the gefitinib arm crossing over to receive open-label lazertinib.
Regarding safety, most patients in both arms experienced treatment-emergent adverse events (TEAEs). The incidence of TEAEs related to study treatment, as well as grade 3 or greater TEAEs related to study treatment, was similar in both groups. One patient in the lazertinib group experienced a TEAEs related to study treatment that resulted in death.
Commonly occurring any-grade TEAEs for the lazertinib group included paresthesia, rash, pruritis, paronychia, and dry skin. For the gefitinib group, common any-grade TEAEs consisted of diarrhea, rash, increased alanine aminotransferase, and increased aspartate aminotransferase.
The LASER301 study was a global, double-blind trial that enrolled treatment-naïve patients with EGFR-mutated locally advanced or metastatic NSCLC eligible for frontline treatment with an EGFR TKI. Lazertinib and gefitinib were given orally once daily, and patients in both arms received treatment until disease progression or withdrawal.
The primary endpoint of the study was investigator-assessed PFS, and secondary endpoints included OS, ORR, DOR, DCR, and safety.
Additionally, lazertinib is also being investigated in the phase III MARIPOSA trial (NCT04487080), evaluating its safety and efficacy in combination with amivantamab and osimertinib in patients with locally advanced or metastatic NSCLC. This trial will enroll approximately 1074 patients and assess various endpoints, including PFS, OS, ORR, DOR, and adverse events.
