Nimotuzumab plus chemotherapy in the posterior-line treatment for lung adenocarcinoma with third-generation epidermal growth factor receptor-tyrosine kinase inhibitors resistance.

Abstract

e20636 Background: Nimotuzumab (a humanized monoclonal antibody) has shown antitumor activity in lung adenocarcinoma. We aimed to evaluate the efficacy and safety of nimotuzumab plus chemotherapy for lung adenocarcinoma with third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) resistance. Methods: Patients with stage IV, metastatic, EGFR-mutated, posterior line therapy failed, and EGFR-TKIs resistant lung adenocarcinoma were collected from Nov, 2018 to Dec, 2023. All patients received nimotuzumab (600 mg every 3 weeks) plus chemotherapy. Overall survival (OS) was the primary endpoint. The second endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Results: A total of 19 patients were screened. As of Sep 20, 2024, the median follow-up was 30.4 months (95% CI: 18.7, not evaluable). The median age was 61.0 years with a range of 42-79. 19 (100.0%) patients had EGFR mutation, 1 (5.3%) patient was treated with second-line treatment, 18 (94.7%) patients with third-line and above treatment. ORR was 26.3% (95% CI: 9.1, 51.2), and DCR was 89.5% (95% CI: 66.9, 98.7). 1-year OS rate was 57.9% (95% CI: 33.2, 76.3) and 2-year OS rate was 23.7% (95% CI: 7.2, 45.5), with the median OS was 12.8 months (95% CI: 5.7, 20.1). 1-year PFS rate was 26.3% (95% CI: 9.6, 46.8), with the median PFS was 4.4 months (95% CI: 3.3, 10.2). Subgroup analysis exhibited that patients with nimotuzumab treatment ≥5 cycles (median PFS=12.39 months, 95% CI: 4.44, 12.91) and no brain metastasis (median PFS=9.23 months, 95% CI: 3.48, NA) have a trend of survival benefit of PFS. Compared to the brain metastasis population, no brain metastasis population had higher 1-year OS rate (66.67% vs. 53.85%, P = 0.09) and 1-year PFS rate (50.00% vs. 15.38%, P = 0.06). The intracranial efficacy after receiving nimotuzumab showed partial response in 7.7% (1/13), stable disease in 76.9% (10/13), and progressive disease in 15.4% (2/13), with an ORR of 7.7% and a DCR of 84.6%. The most frequent Grade 3-4 treatment-related adverse events (AEs) included leukopenia, myelosuppression, neutropenia, thrombopenia, vomiting, nausea, and gastrointestinal reaction. No serious AEs or deaths were monitored. Conclusions: This combination therapy indicated a favorable clinical benefit and tolerable toxicity in the posterior line treatment of patients with third-generation EGFR-TKIs resistant lung adenocarcinoma.