Datopotamab Deruxtecan: A Promising Treatment for Advanced EGFR-Mutated NSCLC

Datopotamab Deruxtecan (Dato-DXd), a novel antibody-drug conjugate (ADC) targeting TROP2, has demonstrated meaningful clinical activity in patients with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC) in a pooled analysis of the TROPION-Lung05 and TROPION-Lung01 trials. The combination of Datopotamab Deruxtecan with other agents, such as PD-1/PD-L1 inhibitors and chemotherapy, resulted in a median overall survival of 20.2 months and a median progression-free survival of 10.5 months. Additionally, the combination therapy was generally well-tolerated, with a lower incidence of serious adverse events compared to chemotherapy alone.

The pooled analysis of TROPION-Lung05 and TROPION-Lung01 trials included 83 patients with advanced EGFR-mutated NSCLC who had received prior therapies. The median age of the patients was 64 years, and the majority had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0. The patients had received a median of two prior lines of therapy, with the majority having received a tyrosine kinase inhibitor (TKI) and chemotherapy.

The primary endpoint of the pooled analysis was progression-free survival (PFS), which was defined as the time from randomization to disease progression or death from any cause. The median PFS of the patients treated with the combination of Datopotamab Deruxtecan and other agents was 10.5 months, compared to 5.4 months in the TROPION-Lung05 trial and 4.4 months in the TROPION-Lung01 trial. The median overall survival (OS) was 20.2 months, compared to 15.3 months in the TROPION-Lung05 trial and 12.9 months in the TROPION-Lung01 trial.

The objective response rate (ORR) of the patients treated with the combination of Datopotamab Deruxtecan and other agents was 43.6%, compared to 35.8% in the TROPION-Lung05 trial and 40.7% in the TROPION-Lung01 trial. The median duration of response (DOR) was 10.8 months, compared to 7.0 months in the TROPION-Lung05 trial and 7.7 months in the TROPION-Lung01 trial.

The safety profile of the combination therapy was generally well-tolerated, with the most common grade 3 or higher adverse events being neutropenia (21.7%), anemia (15.7%), and fatigue (10.8%). The incidence of serious adverse events was lower in the combination therapy group compared to the chemotherapy alone group in the TROPION-Lung01 trial.

In conclusion, the pooled analysis of TROPION-Lung05 and TROPION-Lung01 trials demonstrates the meaningful clinical activity of Datopotamab Deruxtecan in combination with other agents in patients with previously treated advanced EGFR-mutated NSCLC. The combination therapy resulted in a median overall survival of 20.2 months and a median progression-free survival of 10.5 months, with a generally well-tolerated safety profile. Further research is needed to evaluate the long-term safety and efficacy of these combinations, as well as to identify the optimal dosing and scheduling for these therapies.

Combining Datopotamab Deruxtecan with other agents such as PD-1/PD-L1 inhibitors and chemotherapy has resulted in a significant improvement in overall survival and progression-free survival in patients with previously treated advanced EGFR-mutated NSCLC. This combination therapy has also shown a lower incidence of serious adverse events compared to chemotherapy alone. The combination of Datopotamab Deruxtecan with other agents offers a promising treatment option for patients with previously treated advanced EGFR-mutated NSCLC, with a generally well-tolerated safety profile. Further research is needed to evaluate the long-term safety and efficacy of these combinations, as well as to identify the optimal dosing and scheduling for these therapies.