Leptomeningeal metastatic disease responding to carboplatin, pemetrexed, and amivantamab after progression to osimertinib in EGFR exon 21 L858R-Mutated non-small cell lung cancer: Two case reports.

Leptomeningeal metastatic disease (LMD) is associated with a poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who experience disease progression after EGFR tyrosine kinase inhibitor therapy. Amivantamab, an EGFR-mesenchymal-epithelial transition bispecific antibody, has demonstrated clinical efficacy in EGFR-mutated NSCLC; however, its effectiveness in treating symptomatic brain metastases and LMD remains unclear. We report on two cases of LMD that were managed with amivantamab. In Case 1, a 44-year-old woman developed symptomatic LMD during osimertinib therapy. Owing to prior prophylactic whole-brain irradiation during childhood, additional radiotherapy was not feasible. Carboplatin, pemetrexed, and amivantamab treatment resulted in remarkable LMD radiological improvement and gradual neurological symptom resolution. In Case 2, a 69-year-old man developed multiple asymptomatic brain metastases and LMD during osimertinib therapy. Second-line treatment with carboplatin, pemetrexed, and amivantamab resulted in a radiological response. To our knowledge, this is the first report to demonstrate the efficacy of carboplatin, pemetrexed, and amivantamab against LMD progression after osimertinib therapy, suggesting that this regimen may be a therapeutic option for patients with LMD, including those with symptomatic disease. Nevertheless, further studies are warranted to confirm efficacy in this population.