Datopotamab deruxtecan in advanced NSCLC TROPION-Lung01 Phase 3

By. Aaron E. Lisberg, MD,

Date. 11/14/2023

During ESMO 2023, Aaron E. Lisberg, MD, delivered a presentation on the results from the TROPION-Lung01 study, focusing on the clinical question of second-line chemotherapy for advanced metastatic non-small cell lung cancer compared to docetaxel.

The study investigated a novel antibody-drug conjugate targeting TROPION-Lung01, Datopotamab deruxtecan, in a head-to-head comparison with docetaxel. Approximately 300 patients were enrolled and randomized at a one-to-one ratio, regardless of histology or the presence of targetable mutations. The trial had dual primary endpoints—progression-free survival (PFS) and overall survival (OS).

Dr. Lisberg's presentation concentrated on the PFS final analysis in the intention-to-treat population. The data showed a statistically significant benefit across all patients, with a hazard ratio of 0.75. Patients treated with Datopotamab deruxtecan exhibited a median PFS of 4.4 months, compared to 3.7 months in the docetaxel group. However, a closer examination uncovered a notable divergence in benefits based on histology. Non-squamous patients exhibited a hazard ratio of 0.63, translating to nearly two months longer median PFS and nearly three times the objective response rate. In contrast, squamous patients did not experience a similar improvement.

The other primary endpoint, OS, exhibited a trend favoring Datopotamab deruxtecan at the interim analysis, with the most significant benefit observed in non-squamous patients who also demonstrated the greatest PFS advantage.

In addition to efficacy, Dr. Lisberg emphasized the importance of safety data, noting a superior safety profile for Datopotamab deruxtecan compared to docetaxel. The incidence of treatment-related adverse events, especially those of grade three or higher, was lower with Datopotamab deruxtecan, indicating improved patient tolerability. Although practitioners should be aware of unique toxicities such as mucositis and stomatitis, these were generally low-grade and well-managed. The presentation acknowledged the association of DxD-class drugs with interstitial lung disease, but the rates observed were deemed manageable, emphasizing Datopotamab deruxtecan as a viable option for patients with metastatic non-small cell lung cancer, particularly in the non-squamous population, after progression on chemotherapy and other targeted therapies.

Datopotamab deruxtecan in advanced NSCLC TROPION-Lung01 Phase 3

In the TROPION-Lung01 study presented at ESMO 2023, Aaron E. Lisberg, MD, examined second-line chemotherapy options for advanced metastatic non-small cell lung cancer, focusing on the antibody-drug conjugate Datopotamab deruxtecan to surpass the efficacy of traditional docetaxel treatments.