Blood Test Identifies Prostate Cancer Patients Unlikely to Benefit from Cabazitaxel Chemotherapy

Scientists at The Institute of Cancer Research, London have developed a blood test that can predict which men with advanced prostate cancer are unlikely to benefit from cabazitaxel chemotherapy. The research, published in JCI Insight and funded by Sanofi, analyzed samples from more than 200 men and found that chromosomal instability in circulating tumor cells (CTCs) serves as a powerful predictor of treatment resistance.

Addressing Treatment Decision Challenges in Advanced Disease

For men with metastatic castration-resistant prostate cancer (mCRPC), treatment decisions become increasingly complex as the disease progresses. Most patients will have already undergone hormone-targeting therapies such as abiraterone or enzalutamide, as well as initial chemotherapy with docetaxel. When these options fail, oncologists often turn to cabazitaxel, a chemotherapy drug that has been proven to extend survival compared to switching to another hormone-targeting agent.

The landmark CARD trial, which recruited participants from more than 60 sites across 13 European countries, established cabazitaxel as the standard of care for patients progressing on docetaxel and androgen receptor pathway inhibitors (ARPIs). However, some men endure the harsh side effects of chemotherapy—including fatigue, infections and neuropathy—without gaining additional survival time.

Novel Approach to Biomarker Detection

The research team analyzed blood samples from CARD trial participants who had already received docetaxel and progressed within 12 months of starting ARPI treatment. Using an innovative technique, researchers isolated CTCs without traditional enrichment methods such as immunomagnetic capture. They treated blood slides to remove red blood cells, stained them with fluorescent antibodies, and used semi-automated analyses to count CTCs among white blood cells.

A proprietary algorithm categorized cells as chromosomally unstable or 'normal' based solely on cell morphology. The researchers collected samples at three time points: before treatment began, after two cycles of therapy, and at the end of treatment.

Significant Survival Differences Identified

The findings revealed striking differences in outcomes based on chromosomal instability levels. Men with high chromosomal instability in their CTCs had significantly worse outcomes, with median overall survival dropping from approximately 15 months in the low-instability group to just under 9 months in the high-instability group.

Most importantly for clinical practice, when chromosomal instability was high, cabazitaxel did not outperform switching to another hormone-targeting drug. For these patients, chemotherapy offered no survival advantage while still causing significant side effects.

Clinical Implications for Precision Medicine

"Clinicians rely on clinical trial outcomes from large studies such as CARD to guide decision-making for the majority of patients. However, predicting an individual's response to treatment is the holy grail in oncology," said first author Ossian Longoria, Clinical Research Fellow at the ICR. "Now, molecular markers are increasingly entering the picture, offering a deeper look at what drives each patient's cancer."

The blood-based approach avoids invasive biopsies while providing real-time insight into tumor biology. By measuring chromosomal instability in CTCs through a simple blood draw, the test aligns with real-world clinical decision points and could become part of routine care.

Breakthrough in Liquid Biopsy Field

Senior author Professor Johann de Bono, Regius Professor of Cancer Research at the ICR and Consultant Medical Oncologist at The Royal Marsden Hospital, emphasized the significance of the findings: "Our findings build on decades of research at the ICR and elsewhere, and they represent a big breakthrough in the liquid biopsy and circulating tumour cell fields. This is the first prospective confirmation that chromosomal instability predicts cabazitaxel resistance in patients."

The approach also allows oncologists to identify patients with unmet clinical needs, potentially targeting this subpopulation for inclusion in clinical trials testing alternative therapeutic strategies. Professor de Bono noted that further validation work is needed, but the discovery offers hope for treatment decisions that are "smarter, kinder and more effective."