Dr Cooper on Considerations to Help Guide ADC Use in Second-Line NSCLC

Alissa J. Cooper, MD, thoracic oncologist, Memorial Sloan Kettering Cancer Center, highlights key findings and considerations from the phase 3 TROPION-Lung01 trial (NCT04656652), which compared datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate (ADC), with docetaxel as second-line treatment in advanced or metastatic non–small cell lung cancer (NSCLC).

Results from the trial demonstrated a statistically significant improvement in median progression-free survival (PFS) with Dato-DXd compared with docetaxel. Patients who received Dato-DXd (n = 299) achieved a median PFS of 4.4 months (95% CI, 4.2-5.6) vs 3.7 months (95% CI, 2.9-4.2) in the docetaxel arm (n = 305; HR, 0.75; 95% CI, 0.62-0.91; P =.004). However, the improvement was seen as modest given the expectations for this novel therapy, raising questions regarding the optimal use of ADCs in NSCLC, Cooper says. Additional results indicated that the objective response rate was 26.4% (95% CI, 21.5%-31.8%) in the Dato-DXd arm vs 12.8% (95% CI, 9.3%-17.1%) in the docetaxel arm, with a median duration of response of 7.1 months (95% CI, 5.6-10.9) vs 5.6 months (95% CI, 5.4-8.1), respectively.

Cooper notes that an important finding from the trial was the stratification by histology, which revealed that the efficacy of Dato-DXd varied significantly between NSCLC subtypes. Dato-DXd showed greater efficacy in patients with adenocarcinoma. Conversely, in patients with squamous cell carcinoma, docetaxel outperformed Dato-DXd, suggesting potential harm in this subgroup.

Although the TROPION-Lung01 trial highlights the potential role of ADCs in lung cancer, particularly in adenocarcinoma, further research is needed to refine patient selection strategies, optimize efficacy, and minimize exposure to ineffective or potentially harmful therapies. Cooper concludes that a deeper investigation into biomarkers is essential to guide treatment decisions for ADCs like Dato-DXd, focusing not only on histology but also on molecular characteristics that may predict response or resistance.