Amivantamab Plus Lazertinib in EGFR-Mutant Lung Cancer with CNS Metastases

Key Takeaways

• The study included 20 patients with brain metastases and 21 with leptomeningeal disease after prior therapy.
• The primary endpoint was composite best overall response using RECIST 1.1 with RANO brain metastases or RANO leptomeningeal metastases criteria.

In a phase 2 evaluation of patients with EGFR-mutant lung cancer, amivantamab plus lazertinib produced a 50% composite best overall response rate in the brain metastases cohort and 33% in the cytology-diagnosed leptomeningeal disease cohort of a phase 2 evaluation.

Investigators included 20 patients with brain metastases and 21 with leptomeningeal disease, with a median of 2 prior treatment lines and a range of 1 to 7. Mutation groups included 41% EGFR del19, 37% L858R, 12% exon 20 insertions, and 10% uncommon mutations.

The composite response estimates had 95% confidence intervals of 27%-73% in the brain metastases cohort and 15%-57% in the leptomeningeal disease cohort. Median progression-free survival was 5.8 months in patients with brain metastases, with a 95% confidence interval from 3.6 months to not reached, and 7.8 months in the leptomeningeal disease cohort, with a 95% confidence interval of 4.2 to 12.2 months.

Median overall survival reached 17.4 months in the brain metastases cohort, with the reported interval extending from 15.4 months to not reached. In the leptomeningeal disease cohort, median overall survival was 14.4 months, and the reported interval extended from 8.9 months to not reached.

Investigators concluded that amivantamab plus lazertinib showed antitumor activity in patients with EGFR-mutant lung cancers who developed new or progressing brain metastases or leptomeningeal disease after prior therapy. They also stated that including patients with leptomeningeal disease in prospective clinical trials was feasible.