Dato-DXd Shows Efficacy in Lung Cancer, But Safety Issues Remain (ESMO 2023)

Dato-DXd’s Mixed Results in Lung Cancer Trial (ESMO 2023)

ESMO 2023: LBA12

During the Presidential Symposium at the ESMO Congress 2023 in Madrid, a study revealed that datopotamab deruxtecan, an antibody-drug conjugate (ADC), demonstrated longer median progression-free survival (PFS) compared to docetaxel in previously treated patients with advanced non-small-cell lung cancer (NSCLC. The trial involved 604 patients, with the majority having received prior lines of therapy, including immune checkpoint inhibitors (ICI).

Interim data for the co-primary endpoint of overall survival (OS) showed a trend in favor of datopotamab deruxtecan, with confirmed objective response rates (ORR) and longer durations of response compared to docetaxel. Common treatment-related adverse events (TRAEs) with datopotamab deruxtecan included stomatitis and nausea, with fewer severe TRAEs leading to dose adjustments or discontinuation compared to docetaxel.

“We had high hopes that this study would be the first one in a long while to actually change clinical practice – our need for more potent therapies in the second-line setting fuelled our excitement. The absolute increase in PFS in the intention-to-treat population is brief, at just one month, and with interim data, the co-primary endpoint of OS has not been attained. Even though the trial is still maturing for OS, there is little hope that they will succeed in achieving OS gain and highlights that few second-line options currently exist for patients after progression on ICI, and for this reason, she is disappointed by the findings of TROPION-Lung01.”

– Prof. Noemí Reguart from the Hospital Clínic Barcelona, Spain 

In subgroup analyses, the benefits of datopotamab deruxtecan were particularly pronounced in patients with non-squamous histology, providing insights for patient selection in future trials. The TROPION-Lung01 trial is ongoing, and additional trials are exploring combinations of datopotamab deruxtecan with ICIs and chemotherapy as potential first-line treatments for NSCLC to enhance activity and response duration.

These findings offer hope for improved treatment options in advanced NSCLC and the potential to refine patient selection in future clinical trials.


The lung cancer study, known as TROPION-Lung01, reported that Dato-DXd reduced the risk of disease progression or death compared to chemotherapy. While the drug showed a statistically significant benefit in non-squamous patients, overall survival data is still being analyzed, with the hope of showing a favorable benefit-risk profile to regulators. Similarly, in the breast cancer study, TROPION-Breast01, while the rate of ILD was low, mature overall survival data is awaited for a more comprehensive assessment. The absence of overall survival data in both trials is a common occurrence in high-unmet-need scenarios, and the goal is to provide compelling evidence of efficacy to regulators.

Experts believe that having mature overall survival data could play a key role in physicians and patients’ choices when considering therapies. While Dato-DXd appears promising, the availability of mature overall survival data may influence treatment decisions when comparing it to other approved therapies. Daiichi Sankyo and AstraZeneca are closely monitoring the data and keeping the timeline for the final analysis close to the vest, with the lung data expected sometime in 2024 and the breast cancer timeline undisclosed.

The safety and efficacy findings for Dato-DXd offer a valuable glimpse into the intricate considerations that guide drug development and regulatory approvals, particularly in scenarios where patients face limited treatment options.

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