In TROPION-Lung01, Dato-DXd Continues to Show Promise in NSCLC

Datopotamab deruxtecan (Dato-DXd), the TROP2-directed antibody-drug conjugate, numerically improved overall survival (OS) compared with docetaxel in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) treated with at least 1 prior line of therapy, but the improvement was not statistically significant.^1,2

Findings from the phase 3 TROPION-Lung01 study (NCT04656652) were presented at the 2024 World Conference on Lung Cancer. In the overall trial population, Dato-DXd delivered an OS of 12.9 months vs 11.8 months for docetaxel (HR, 0.94; 95% CI, 0.78-1.14; P =.530). In a subgroup of patients with nonsquamous NSCLC, Dato-DXd improved OS by 2.3 months vs docetaxel (14.6 vs 12.3; HR, 0.84; 95% CI, 0.68-1.05). This improvement was observed regardless of actionable genomic mutations.

However, even though OS improvement did not reach statistical significance, the numerical improvement plus the stastically significant improvement in progression-free survival (PFS) indicate promise for the agent in this patient population.

“Despite many efforts to surpass docetaxel with novel approaches in previously treated advanced or metastatic non–small cell lung cancer, patients only survive for about 1 year. For datopotamab deruxtecan to show a statistically significant improvement in progression-free survival along with improved response rate, duration of response and an overall survival improvement numerically consistent with progression-free survival is clinically meaningful for patients with nonsquamous lung cancer,” said Jacob Sands, MD, medical oncologist at Dana-Farber Cancer Institute and investigator in the trial, in a press release.¹

TROPION-Lung01 previously met its primary end point of PFS, and data were presented at the 2023 European Society for Medical Oncology (ESMO) Congress.³ Here, patients in the intention-to-treat population who received Dato-DXd (n = 299) achieved a median PFS of 4.4 months (95% CI, 4.2-5.6) vs 3.7 months with docetaxel (n = 305), showing a statistically significant improvement (HR, 0.75; 95% CI, 0.62-0.91; P =.004).

Further, the objective response rate was 26.4% (95% CI, 21.5%-31.8%) in the Dato-DXd arm vs 12.8% in the docetaxel arm (95% CI, 9.3%-17.1%), with median durations of response of 7.1 months (95% CI, 5.6-10.9) vs 5.6 months (95% CI, 5.4-8.1), respectively.

REFERENCES:

1. Datopotamab deruxtecan showed median overall survival of 14.6 months in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 phase III trial. News release. AstraZenca. September 9, 2024. Accessed September 10, 2024. https://tinyurl.com/3hbfnjvf

2. Sands J, Lisberg A, Okamoto I, et al. Datopotamab deruxtecan vs docetaxel in patients with non-small cell lung cancer: final overall survival from TROPION-Lung01. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA08.03.

4. Ahn M, Lisberg AE, Paz-Ares L et al. LBA12 - Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01. Abstract presented at: ESMO Congress 2023, October 20-24, 2023.