Datopotamab deruxtecan: Expanding treatment options for patients with EGFR-positive non-small cell lung cancer

Despite significant advances in the treatment of patients with EGFR-positive metastatic non-small cell lung cancer (NSCLC), a number of unanswered questions remain. EGFR tyrosine kinase inhibitors (EGFR TKIs), both monotherapy and in combination regimens, are undoubtedly the optimal first-line therapy and can significantly improve long-term outcomes. After disease progression with targeted therapy, we typically use standard platinum-based therapy or a quadruple regimen (atezolizumab, paclitaxel, carboplatin, and bevacizumab), which limits our options. Further treatment is limited to cytostatics, typically used alone, with expectedly low efficacy. Thus, there is an unmet need for subsequent lines of therapy for these patients. The objective of this study was to present the results of clinical and preclinical studies of datopotamab deruxtecan to confirm its benefit in patients with metastatic EGFR-positive NSCLC. The phase I clinical trials TROPION-PanTumor01 and TROPION-PanTumor02 demonstrated encouraging results and satisfactory tolerability in a cohort of patients with NSCLC. In the randomized TROPION LUNG01 study, datopotamab deruxtecan, administered at a dose of 6 mg/kg intravenously every 3 weeks, was compared with docetaxel in a population of previously treated patients with non-small cell lung cancer. The clear advantage of datopjtamab over docetaxel, especially in patients with EGFR mutations, led to its further study in this cohort of patients in the Phase II TROPION LUNG 05 trial. Subsequently, a pooled analysis of the efficacy of datopotamab deruxtecan was conducted in EGFR-positive patients participating in the TROPION LUNG01/05 trials. Datopotamab demonstrated the best results to date in terms of immediate efficacy, progression-free survival, and overall survival in pretreated EGFR-positive patients. The drug was well-tolerated. These results led to the approval of datopotamab deruxtecan for clinical use in patients with EGFR-positive NSCLC following progression on EGFR-TKIs and platinum-based chemotherapy, opening the door to further personalized therapy.