Dato-DXd Misses Significance for OS in Advanced Non-Small Cell Lung Cancer

Overall survival (OS) data from the phase 3 TROPION-Lung01 trial (NCT04656652) compared datopotamab deruxtecan (Dato-DXd) with docetaxel demonstrated numerical improvement but not statistical significance in the overall trial population of patients with advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least 1 prior line of therapy.¹

In a prespecified subgroup analysis of patients with nonsquamous NSCLC, Dato-DXd did show a clinically meaningful improvement in OS vs docetaxel, the current standard of care.

“The improvement in overall survival seen with datopotamab deruxtecan coupled with the previously reported clinically meaningful progression-free survival, more than doubling of overall response and prolonged duration of response compared to docetaxel suggest that this TROP2-directed antibody-drug conjugate could potentially become an important new treatment for patients with nonsquamous non-small cell lung cancer in this advanced setting. These data will support our ongoing discussions with regulatory authorities globally to potentially bring datopotamab deruxtecan to patients as quickly as possible and mark another step forward in creating new standards of care for patients with cancer,” said Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, in a press release.

TROPION-Lung01 previously met its dual primary end point of progression-free survival (PFS). Data presented at the 2023 European Society for Medical Oncology showed that Dato-DXd led to a statistically significant improvement in PFS in the overall trial population and a clinically meaningful improvement in PFS among patients with nonsquamous histology.

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 in the docetaxel arm (n = 305; HR, 0.75; 95% CI, 0.62-0.91; P =.004). The objective response rate (ORR) 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 a median duration of response (DORs) of 7.1 months (95% CI, 5.6-10.9) vs 5.6 months (95% CI, 5.4-8.1), respectively.²

In February 2024, the FDA accepted the biologics license application for Dato-DXd in NSCLC based on the PFS data from TROPION-Lung01. A decision on the application is expected in the fourth quarter of 2024. A regulatory application for Dato-DXd is also being considered in the European Union.³

REFERENCES:

1. Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 phase III trial. News release. AstraZeneca. May 27, 2024. Accessed May 29, 2024. https://tinyurl.com/27hbnzx9

2. Ahn MJ, Lisberg A, Paz-Ares L, et al. Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): results of the randomized phase 3 study TROPION-Lung01. Ann Oncol. 2023;34(suppl 2):S1305-S1306. doi:10.1016/j.annon

3. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed May 29, 2024. http://tinyurl.com/w595xw6u