A combined study of the TROPION-Lung05 and TROPION-Lung01 trials, which was shown at the 2024 ESMO Asia Congress (ESMOAsia24), suggests that datopotamab deruxtecan (Dato-DXd) could be a major step forward in treating advanced lung cancer. The findings demonstrate significant tumour responses in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who had run out of prior treatment options. 

The TROP2-directed DXd antibody-drug conjugate (ADC) datopotamab deruxtecan was created by Daiichi Sankyo and AstraZeneca. It had a confirmed objective response rate (ORR) of 42.7% in 117 patients and a disease control rate (DCR) of 86.3%. The results are undeniably compelling for a population that has previously demonstrated limited responsiveness to therapies like osimertinib, highlighting the drug's significant potential. 

The trials showed five complete responses (4.3%) and 45 partial responses (38.5%), with 41% of patients exhibiting stable disease. The median duration of response (DOR) reached 7.0 months, with progression-free survival (PFS) and overall survival (OS) recorded at 5.8 and 15.6 months, respectively. In patients previously treated with osimertinib, the outcomes demonstrated consistency, indicating a strong performance across various subgroups. 

"Initial treatment with EGFR tyrosine kinase inhibitors has undeniably transformed outcomes for patients with advanced EGFR-mutated NSCLC; however, it is an unfortunate reality that most patients will ultimately face disease progression," asserted Dr. Myung-Ju Ahn, Professor at Samsung Medical Centre, Seoul. "The results clearly indicate that datopotamab deruxtecan stands to provide a crucial option in the pretreated metastatic setting." 

The safety profile firmly aligns with prior data, and no new concerns have emerged. Stomatitis occurred in 59% of cases, alopecia in 49%, and nausea in 46%. These treatment-related adverse events are significant and cannot be overlooked. In 23% of patients, grade 3 or higher events were observed, while there were absolutely no cases of grade 4 or 5 stomatitis or interstitial lung disease. 

The findings hold immense significance for the expanding group of patients facing advanced EGFR-mutated NSCLC. "The results of this pooled analysis clearly demonstrate the potential of datopotamab deruxtecan in patients experiencing disease progression after multiple lines of prior treatment," asserted Dr. Ken Takeshita, Global Head of R&D, Daiichi Sankyo. 

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, asserted, "These results demonstrate that datopotamab deruxtecan can enhance outcomes for patients whose disease has developed resistance to existing treatments." The data decisively paves the way for our upcoming trial in patients with TROP2-QCS biomarker-positive tumors. 

The collaboration between Daiichi Sankyo and AstraZeneca has filed for regulatory approval in the U.S., showcasing promising results that could lead to significant advancements in the standard of care for metastatic lung cancer. 

Further studies are essential to confirm long-term benefits, yet datopotamab deruxtecan stands as a significant advancement for patients with EGFR-mutated NSCLC. The ability to deliver significant tumor responses in a heavily pretreated population highlights its transformative potential in oncology.