Overcoming Atypical EGFR Challenges With a Novel Approach

Atypical EGFR mutations, such as S768I, L861Q, and G719X, are often resistant to traditional EGFR TKIs. Afatinib (Gilotrif) is the only approved TKI for these mutations, but its effectiveness is limited.

The CHRYSALIS-2 study (NCT04077463) evaluated the combination of amivantamab (Rybrevant), an EGFR-MET bispecific antibody, and lazertinib (Lazcluse), a CNS-penetrant EGFR TKI, in patients with atypical EGFR-mutated advanced NSCLC.

The combination showed promising results, with an overall response rate (ORR) of 51%. In treatment-naïve patients, the ORR was even higher at 55%, with a median progression-free survival (mPFS) of 19.5 months. The combination was also effective in patients with prior afatinib treatment.

The most common adverse effects were primarily EGFR- and MET-related toxicities, which were generally manageable. VTE (venous thromboembolism) was a significant concern, occurring in 30% of patients.

The combination of amivantamab and lazertinib demonstrates significant potential for patients with atypical EGFR-mutated advanced NSCLC, offering a new treatment option for this challenging patient population.

Here, Byoung Chul Cho, MD, PhD, medical oncologist at Yonsei Cancer Center in South Korea, discusses the implications of these findings.

Transcription:

0:05 | With our study, we demonstrated that amivantamab plus lazertinib has important activity in patients with atypical EGFR-mutant lung cancer. We demonstrated the longest median PFS with this combination, and it is almost double that we see of classical EGFR TKIs. In addition to PFS, we also demonstrated promising overall survival with a median follow-up of 17 months. Median survival in first-line setting was not estimable, which is promising given the fact that median overall survival with available EGFR TKI treatment is known to be around 20 to 25 months.

1:01 | Lastly, we demonstrated superior efficacy of amivantamab plus lazertinib in the first-line setting compared [with] a variable treatment in the first-line setting from real-world data. I assume all these data suggest the potential of amivantamab plus lazertinib in the first-line setting.