Patritumab Deruxtecan Shows Promise in HR+/HER2- Metastatic Breast Cancer After CDK4/6 Inhibitor Resistance
Key Insights
Patritumab deruxtecan (HER3 (search)-DXd) demonstrates a 53.5% response rate in heavily pre-treated HR+/HER2- metastatic breast cancer (search) patients resistant to CDK4/6 inhibitors.
The ICARUS-BREAST01 phase II trial reports a median progression-free survival of 9.4 months with patritumab deruxtecan, suggesting improved outcomes compared to conventional third-line chemotherapies.
Researchers identified potential factors influencing treatment response, including the distribution of HER3 (search)-positive cells within the tumor and drug-induced immune response.
A phase II trial, ICARUS-BREAST01, presented at ESMO 2024, reveals promising results for patritumab deruxtecan (HER3 (search)-DXd) in patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (search) whose tumors have developed resistance to CDK4/6 inhibitors and one line of chemotherapy. The study, a French academic multi-center trial sponsored by Gustave Roussy (search), evaluated the activity, safety, and biomarkers of response and resistance to this antibody-drug conjugate.
Study Design and Patient Population
The ICARUS-BREAST01 trial enrolled 99 adult patients who received patritumab deruxtecan every three weeks until disease progression or unacceptable toxicity. All patients had HR+/HER2- metastatic breast cancer (search) that had progressed on CDK4/6 inhibitors and one prior line of chemotherapy, representing a population with limited treatment options.
Efficacy and Safety Results
As of the data cutoff on April 16, 2024, 19 patients remained on treatment. With a median follow-up of 15.3 months, the objective response rate (ORR) was 53.5%. The median duration of response (DoR) was 8.7 months, and the median progression-free survival (PFS) was 9.4 months. Common adverse events included fatigue, nausea, and diarrhea.
Dr. Barbara Pistilli, head of the breast pathology committee at Gustave Roussy (search), noted, "With conventional treatments used as a third-line chemotherapy, the response rate is lower and progression-free survival is in the region of 4 to 6 months, so these results are very encouraging."
Biomarker Analysis and Resistance Factors
Exploratory analyses identified potential factors influencing response to patritumab deruxtecan. The level of HER3 (search) receptor expression in the tumor did not correlate with treatment response. However, the distribution of HER3-positive cells within the tumor and the intra-tumoral distribution of the drug appeared to be associated with response. Additionally, the researchers found that activating a drug-induced immune response against the tumor may lead to a better response.
Implications and Future Directions
Patritumab deruxtecan, an antibody-drug conjugate that links an anti-HER3 (search) antibody to a topoisomerase I inhibitor, represents a potential new therapeutic strategy for advanced HR+ breast cancer (search). The ICARUS-BREAST01 trial suggests that this agent can overcome resistance to CDK4/6 inhibitors and provide meaningful clinical benefit in heavily pre-treated patients.
"This drug-antibody conjugate, patritumab deruxtecan, therefore appears to be a promising potential new therapy in advanced forms of hormone-dependent breast cancer (search), although further studies are needed to confirm these data," Dr. Pistilli concluded. Further research is warranted to validate these findings and to identify predictive biomarkers that can help guide treatment decisions. The study was conducted in partnership with Daiichi Sankyo and MSD as part of the Unlock medical scientific program at Gustave Roussy (search).