Impacts of datopotamab deruxtecan (dato-DXd) on advanced non-small cell lung cancer (NSCLC): a literature review

Keywords

Datopotamab deruxtecan - Dato-DXd - advanced non-small cell lung cancer

Introduction: Datopotamab duruxtecan (Dato-DXd) is a monoclonal antibody conjugated to a potent topoisomerase I inhibitor, targeting TROP2. Currently, Dato-DXd is employed in the treatment of certain malignancies, including non-small cell lung cancer (NSCLC). The use of this medication, in this context, has brought promising results in objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), along with favorable safety and tolerability profiles, positioning it as an alternative to systemic chemotherapy.

Objective: To review the clinical effects of Dato-DXd in NSCLC, as well as to provide data on OS, PFS, response rate, and adverse events.

Method: This is a literature review whose content was obtained from the PubMed and LILACS databases, using the following search strategy: the MeSH descriptors “datopotamab deruxtecan” and “Lung cancer” were used, and the Boolean operator “and” was included between them. The search was conducted on August 10, 2024. In PubMed, nine articles were found, while no studies were identified in LILACS. All articles that had a title and abstract consistent with the studied topic were included. Works that were not published in English were excluded. Thus, a sample of 9 articles was reached (n = 9).

Results: The phase III TROPION-Lung01 trial, which randomized 604 patients with NSCLC into two arms, one to receive Dato-DXd 6mg/kg and the other to Docetaxel 75 mg/m2 every 3 weeks, with a median follow-up of 12.9 months, favoring the Dato-DXd arm, presenting PFS of 5.5 months versus 3.6 months (HR 0.63 - 95% CI 0.51-0.79), with statistical significance (p-value 0.004). The multicenter phase I TROPION-PanTumor01 trial, which included 180 patients with NSCLC, revealed that Dato-DXd, generally used in the third-line of therapy, presented manageable side effects, such as nausea (64% of patients), mucositis/stomatitis (60%), fatigue (28%) and alopecia (42%), with interstitial lung disease or pneumonitis in 6% of patients. Only 10% required dose reduction, and 14% had to discontinue the drug. The same study reported an OS of 11.4 months (95% CI, 7.1 to 20.6 months) and an ORR of 26%.

Conclusion: There was promising antitumor activity of Dato-DXd as monotherapy and a manageable safety profile in patients with advanced NSCLC, previously treated with several lines, still obtaining encouraging results.

Corresponding author: Antonio Marlos Duarte de Melo (e-mail: [e-mail]).