KEY TAKEAWAYS
- The MARIPOSA phase 3 trial aimed to assess the efficacy and safety of lazertinib versus osimertinib in EGFR-mutant advanced NSCLC.
- The primary endpoints were to determine PFS, ORR, DoR, OS, and safety.
- Researchers observed similar efficacy and safety, supporting lazertinib as a promising option for EGFR-mutant NSCLC.
Lazertinib is an oral, central nervous system-penetrant, 3rd-generation EGFR tyrosine kinase inhibitor (TKI) that has demonstrated significant improvement in progression-free survival (PFS) compared to gefitinib in treatment-naïve, patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) (Cho JCO 2023).
In the phase 3 MARIPOSA study (NCT04487080), the combination of lazertinib with amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, showed a significant PFS improvement over osimertinib in the same patient population (HR, 0.70; 95% CI, 0.58-0.85; P < 0.001; Cho Ann Oncol 2023). The MARIPOSA trial also featured a lazertinib monotherapy arm to evaluate the contribution of each component in the combination therapy.
The 1 trial to prospectively compare 2, 3rd-generation EGFR-TKIs in a randomized, double-blind setting. Se Hoon Lee and the team aimed to assess the efficacy and safety of lazertinib compared to osimertinib in EGFR-mutant advanced NSCLC.
They performed an inclusive analysis in the MARIPOSA trial, where 1,074 patients with EGFR-mutant advanced NSCLC were randomized in a 2:2:1 ratio to receive amivantamab plus lazertinib, osimertinib monotherapy, or lazertinib monotherapy. These exploratory analyses focused specifically on the 216 patients randomized to receive lazertinib (240 mg daily) and the 429 patients randomized to osimertinib (80 mg daily), all treated in a double-blind fashion.
Serial brain imaging with MRI was mandatory for all participants to monitor central nervous system involvement. Key efficacy endpoints included PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1 criteria, overall response rate (ORR), duration of response (DoR), and overall survival (OS). Safety profiles were also evaluated across both treatment groups.
The median PFS by BICR was 18.5 months (95% CI, 14.8-20.1), at a median follow-up of 22.0 months, for patients receiving lazertinib vs 16.6 months (95% CI, 14.8-18.5) for those on osimertinib (HR, 0.98; 95% CI, 0.79-1.22). The ORR was 83% (95% CI, 77-88) for lazertinib and 85% (95% CI, 81-88) for osimertinib.
Among confirmed responders, the median DoR was 16.6 months (95% CI, 14.8-20.2) for lazertinib and 16.8 months (95% CI, 14.8-18.5) for osimertinib. At interim survival analysis, the median OS was not estimable for either treatment arm (HR, 1.00; 95% CI, 0.73-1.38).
Moreover, an evaluation of PFS in subgroups of high-risk disease was performed. For patients with a history of brain metastases, the median PFS was 16.4 months (95% CI, 12.9-19.4) for lazertinib vs 13.0 months (95% CI, 12.2-16.4) for osimertinib (HR, 0.90; 95% CI, 0.65-1.25).
Patients with detectable circulating tumor DNA at baseline, the median PFS was 18.4 months (95% CI, 14.6-20.1) for lazertinib compared to 14.8 months (95% CI, 12.9-16.6) for osimertinib (HR, 0.88; 95% CI, 0.66-1.17). For patients with TP53 co-mutations, the median PFS was 14.6 months (95% CI, 11.0-19.4) for lazertinib vs 12.9 months (95% CI, 11.1-14.7) for osimertinib (HR, 0.85; 95% CI, 0.58-1.23).
The safety profiles of lazertinib and osimertinib were similar, with EGFR-related adverse events (AEs) being the most frequent. Most AEs were grade 1-2. Higher incidences of diarrhea, thrombocytopenia, leukopenia, and QT interval prolongation were observed with osimertinib, whereas lazertinib was associated with higher rates of rash and paresthesia. Treatment-related AEs leading to discontinuations were comparable between the 2 treatment arms.
The study concluded that efficacy and safety outcomes were comparable between lazertinib and osimertinib in patients with EGFR-mutant advanced NSCLC. Both treatments demonstrated strong clinical activity, including in patients with high-risk features such as brain metastases and TP53 co-mutations. Lazertinib was identified as a potential new treatment option, offering similar benefits to osimertinib while presenting a distinct safety profile.
The trial was sponsored by Janssen Research & Development, LLC.
Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/737
Clinical Trial: https://clinicaltrials.gov/study/NCT04487080
Lee S.H, Cho B.C, Hayashi H, et al. (2024). “Lazertinib vs Osimertinib in 1L EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis from MARIPOSA.” Presented at IASLC-WCLC 2024, September 8, 2024; Singapore.
