Datopotamab deruxtecan extends PFS vs chemo for HR+/HER2- breast cancer

Dr Aditya Bardia - Mass General Cancer Center, Boston, USA

On behalf of my co-authors it was my pleasure to present the results of the TROPION-Breast01 which looked at a TROP2 ADC, datopotamab deruxtecan, versus standard chemotherapy for patients with metastatic hormone receptor positive breast cancer. In terms of a brief background, patients with endocrine resistant hormone receptor positive breast cancer usually receive chemotherapy but chemotherapy can be associated with significant toxicity – myelosuppression, peripheral neuropathy – and is also not very active in this setting with a response rate of about 15-20%, progression free survival of 3-4 months. There rea newer TROP2 ADCs either approved or being developed which have shown efficacy but can be associated with toxicity as well –neutropenia, thrombocytopenia and diarrhoea.

So clinically there’s an unmet need for better therapies in this setting. Dato-DXd is a novel TROP2 antibody-drug conjugate. It has several unique properties in terms of the design which can reduce the toxicity that’s associated with the ADC. It has a more stable linker, it requires tumour selective delivery and it has a bystander effect which can address tumour heterogeneity.

So TROPION-Breast01 looked at Dato-DXd versus standard chemotherapy in patients with endocrine resistant hormone receptor positive breast cancer. The primary endpoint was progression free survival. The bottom line – the study met its primary endpoint. There was an improvement in progression free survival with Dato-DXd with a hazard ratio of 0.63, so that’s a 37% lower risk of disease progression or death with Dato-DXd as compared to standard chemotherapy. The median progression free survival with the Dato-DXd was about 7 months.

The response rate with Dato-DXd was also higher as compared to standard chemotherapy. In terms of overall survival there was a trend towards improvement in overall survival. The results of overall survival are not mature and additional follow-up is needed.

In terms of safety the incidence of grade 3 or higher toxicity was no worse with Dato-DXd as compared to standard chemotherapy, which is a bit different from a number of other studies where usually the AEs are higher in the intervention arm as compared to the control arm. But here the incidence of grade 3 AEs were lower with Dato-DXd as compared to standard chemotherapy. It speaks to the mechanism of the antibody drug conjugate and the stable linker that it has.

In terms of side effects that were seen with Dato-DXd, those included mucositis as well as dry eye. With standard chemotherapy the usual toxicities were seen – myelosuppression, neutropenia, neutropenic fever, anaemia and the usual side effects we see with chemotherapy.

So, overall, TROPION-Breast01 met its primary endpoint. It showed that Dato-DXd had superior efficacy as compared to standard chemotherapy and, if anything, lower rates of grade 3 or higher adverse events as compared to standard chemotherapy. So if approved by the FDA this would be a novel therapeutic option for patients with hormone receptor positive metastatic breast cancer. We’re really excited about the results.