The TROP-2–directed antibody-drug conjugate datopotamab deruxtecan may significantly improve progression-free survival in patients with metastatic non–small cell lung cancer (NSCLC), especially in patients with non–squamous cell tumors, according to new findings simultaneously published by Ahn et al in the Annals of Oncology and presented by Lisberg et al at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract LBA12).
Study Methods and Results
In the phase III TROPION-Lung01 trial, researchers randomly assigned 604 patients with pretreated metastatic NSCLC to receive datopotamab deruxtecan (n = 299) or the standard-of-care second-line chemotherapy drug docetaxel (n = 305)—with the goal of comparing the effectiveness and tolerability of both drugs. The researchers recruited patients both with and without genetic driver mutations such as EGFR and required them to have received multiple therapies for metastatic NSCLC prior to enrollment.
Patients who received datopotamab deruxtecan experienced 25% reductions in their risk of disease progression or mortality compared with those who received docetaxel. Over 75% of the patients who were involved in the trial had nonsquamous tumors, and among these patients, those who received datopotamab deruxtecan saw a 37% reduced risk of disease progression or mortality; whereas those who had squamous tumors did not appear to derive therapeutic benefit from the novel treatment.
Additionally, a trend in favor of datopotamab deruxtecan was observed in the interim overall survival analysis. In those assessments of patient survival following receipt of therapy, the improvement was most pronounced in the patients with nonsquamous tumors, with a reduction in the risk of mortality of 23% after taking datopotamab deruxtecan.
Further, compared with those who received docetaxel, the patients who received datopotamab deruxtecan experienced tumor shrinkage of 26.4% vs 12.8%. For those with nonsquamous tumors, tumor shrinkage increased to 31.2% in the datopotamab deruxtecan group.
The researchers reported that the overall safety profile of datopotamab deruxtecan was superior to docetaxel, with fewer patients experiencing high-grade drug-related toxicities in the datopotamab deruxtecan group (25%) vs the docetaxel group (41%). The most common side effects of datopotamab deruxtecan included mild to moderate mouth sores and nausea. There were also fewer severe side effects leading to dose reductions or treatment discontinuations in the datopotamab deruxtecan group compared with the docetaxel group.
Conclusions
The researchers commented that their new findings were encouraging, since the current standard of care, docetaxel, was associated with modest benefit and substantial toxicity, suggesting that datopotamab deruxtecan may have the potential to be a novel therapeutic option for patients with nonsquamous NSCLC.
“[Datopotamab deruxtecan] is the first antibody-drug conjugate in metastatic [NSCLC] to demonstrate a statistically significant improvement in progression-free survival over … docetaxel, while evidencing a more favorable safety profile due to its unique ability to selectively deliver a potent chemotherapy directly into tumor cells,” emphasized co–study author Aaron Lisberg, MD, Assistant Professor of Medicine and a thoracic medical oncologist at the University of California, Los Angeles (UCLA) Health Jonsson Comprehensive Cancer Center and the David Geffen School of Medicine. “While there was an overall reduction of disease progression, the data clearly indicates that this benefit was primarily driven by patients with nonsquamous tumors,” he said.
Datopotamab deruxtecan is currently being evaluated for its potential as first-line therapy in patients with newly diagnosed metastatic NSCLC in the TROPION-Lung07 (ClinicalTrials.gov identifier NCT05555732) and TROPION-Lung08 (NCT05215340) studies.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
