As reported in the Journal of Clinical Oncology by Ahn et al, the phase III TROPION-Lung01 trial showed significantly improved progression-free survival—but not overall survival—with the TROP2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) vs docetaxel in patients with pretreated advanced or metastatic non–small cell lung cancer (NSCLC).

Study Details

In the global open-label trial, 604 patients were randomly assigned between February 2021 and November 2022 to receive Dato-DXd at 6 mg/kg (n = 299) or docetaxel at 75 mg/m² (n = 305) every 3 weeks until disease progression or unacceptable toxicity. For the Dato-DXd group vs docetaxel group, 78% vs 77% had nonsquamous histology, 41% vs 41% were White, and 40% vs 39% were Asian. The dual primary endpoints were progression-free survival and overall survival 

Progression-Free and Overall Survival

Median follow-up for progression-free survival was 10.9 months (95% confidence interval [CI] = 9.8–12.5 months) in the Dato-DXd group and 9.6 months (95% CI = 8.2–11.9 months) in the docetaxel group. Median progression-free survival was 4.4 months (95% CI = 4.2–5.6 months) in the Dato-DXd group vs 3.7 months (95% CI = 2.9–4.2 months) in the docetaxel group (hazard ratio [HR] = 0.75, 95% CI = 0.62–0.91, P = .004). Among patients with nonsquamous tumors, median progression-free survival was 5.5 months (95% CI = 4.3–6.9 months) in the Dato-DXd group vs 3.6 months (95% CI = 2.9–4.2 months) in the docetaxel group (HR = 0.63, 95% CI = 0.51–0.79).

Median follow-up for overall survival was 23.1 months (95% CI = 22.0–24.8 months) in the Dato-DXd group and 23.1 months (95% CI = 21.7–24.2 months) in the docetaxel group. Median overall survival was 12.9 months (95% CI = 11.0–13.9 months) with Dato-DXd vs 11.8 months (95% CI = 10.1–12.8 months) with docetaxel (HR = 0.94, 95% CI = 0.78–1.14, P = .530). Among patients with nonsquamous histology, median overall survival was 14.6 months (95% CI = 12.4–16.0 months) with Dato-DXd vs 12.3 months (95% CI = 10.7–14.0 months) with docetaxel (HR = 0.84, 95% CI = 0.68–1.05). Among patients with squamous histology, median progression-free survival was 2.8 vs 3.9 months (HR = 1.41, 95% CI = 0.95–2.08), and median overall survival was 7.6 vs 9.4 months (HR = 1.32, 95% CI = 0.91–1.92).

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 25.6% of the Dato-DXd group and 42.1% of the docetaxel group; the most common adverse events included stomatitis (6.7%) and anemia (4.0%) in the Dato-DXd group and neutropenia (23.4%) and leukopenia (13.1%) in the docetaxel group. Serious treatment-related adverse events occurred in 11.1% vs 12.8% of patients.

Treatment-related adverse events led to treatment discontinuation in 8.1% vs 12.1%. Adjudicated any-grade drug-related interstitial lung disease (ILD)/pneumonitis occurred in 8.8% vs 4.1%. Treatment-related death occurred in three patients (1%) in the Dato-DXd group, as a result of ILD/pneumonitis in two and sepsis in one, and in two patients (0.7%) in the docetaxel group, from ILD/pneumonitis and septic shock.

The investigators concluded: “Dato-DXd significantly improved [progression-free survival] versus docetaxel in patients with advanced/metastatic NSCLC, driven by patients with nonsquamous histology. [Overall survival] showed a numerical benefit but did not reach statistical significance. No unexpected safety signals were observed.”

Jacob Sands, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by Daiichi Sankyo. For full disclosures of the study authors, visit ascopubs.org.