Real-world efficacy and safety of amivantamab in EGFR exon-20-mutant non-small cell lung cancer in a French early-access program: Amexon 20 GFPC study.

BACKGROUND

Amivantamab is a bispecific anti-EGFR-MET antibody approved to treat non-small cell lung cancers (NSCLCs) harbouring EGFR exon 20 insertions (EGFR-exon20ins).

METHODS

We conducted a retrospective, multicentre analysis of consecutive patients with EGFR-exon20ins NSCLC treated with ≥ 1 dose of amivantamab in a French early-access programme (09/03/2021-04/30/2022). The primary endpoint was real-world progression-free survival (rwPFS). Secondary endpoints included treatment duration, overall survival (OS), outcomes in patients with brain metastases (BMs), and safety.

RESULTS

Thirty-nine patients were included (median age: 60 years; 64.1 % female, 54 % never-smokers, 33.3 % with ECOG performance status (ECOG-PS) ≥ 2; 66.7 % with BMs at baseline). Amivantamab was administered as second-line therapy in 30 % and third-line or later in 70 %. Patients received a median of 10 doses (range: 1-47) over a median [95 % CI] of 3.4 [1.8-6.3] months. Among 37 evaluable patients, partial responses and disease control were achieved in 35 % [17 %-49 %] and 62 % [44 %-76 %], respectively; median response duration was 5.8 [2.3-11.9] months. In patients with BM, partial response occurred in 23 % and disease control in 69 %. After a median follow-up of 11.3 [8-16.7] months, median rwPFS and OS were 3.5 [2.6-5.8] and 11.3 [8-17.8] months, respectively. Outcomes were 2.8 [3.5-17.8] and 8.7 [3.5-17.8] months in patients with BMs, and 7.6 [1.6-13.5] and 16.2 [8.3-NR] months in those without BMs, respectively. Grade ≥ 3 adverse events occurred in 11 patients (28.2 %), mainly skin toxicity (12.8 %) and infusion reactions (5.1 %), leading to dose reductions in 17.9 % and permanent discontinuation in 10.3 %. On multivariate analysis, ECOG-PS ≥ 2 was the only negative prognostic factor for both rwPFS and OS.

CONCLUSION

Amivantamab demonstrated clinical activity in EGFR-exon20ins-NSCLC, including in patients with BM, with a manageable safety profile.