This impactful clinical trial aimed to go beyond outlining disparities in outcomes; it took a proactive step toward addressing these gaps to foster equity in breast cancer care. Its findings show that research, when specifically tailored to underrepresented populations, yields positive results.

In a study carried out by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), Black patients with early-stage breast cancer who received docetaxel chemotherapy every three weeks experienced fewer instances of drug-induced peripheral neuropathy and required significantly fewer dose reductions than those who underwent weekly paclitaxel treatment. The trial, EAZ171, is groundbreaking, marking the first National Cancer Institute (NCI)-backed study to focus on enrolling a minority or underserved group in order to assess treatment toxicity rather than efficacy, particularly in cases where known disparities exist.

The trial's results were unveiled at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago and have been published in the Journal of Clinical Oncology.

"Historically, clinical trials in America have suffered from a critical underrepresentation of Black patients. This is a significant challenge when considering the wide racial disparities in cancer outcomes. Our goal extended beyond just identifying these disparities; we sought to understand them better and take steps toward solutions to improve equity in breast cancer treatment," explained Dr. Tarah J. Ballinger, the study's presenter and medical director of breast cancer prevention at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. Dr. Ballinger is also the Vera Bradley Foundation Scholar in Breast Cancer Research and an Associate Professor at Indiana University School of Medicine.

Despite having a 4% lower incidence of breast cancer than white patients in the U.S., Black women face a 40% higher breast cancer mortality rate, according to the American Cancer Society. Importantly, this elevated death rate is not explained by the cancers being more aggressive in Black patients.

Previous research has shown that Black individuals, as well as those of African ancestry, are more likely to suffer from peripheral neuropathy – painful nerve damage often caused by chemotherapy, starting in the hands or feet. Genetic factors likely play a role in this, and higher rates of neuropathy are linked to chemotherapy dose reductions and decreased treatment efficacy.

The EAZ171 study was designed to validate genetic predictors of taxane-induced peripheral neuropathy (TIPN), specifically aiming to determine the best taxane-based chemotherapy for minimizing neuropathy in Black patients with early-stage breast cancer. The trial enrolled 249 participants, all receiving taxane-based chemotherapy per standard guidelines: either docetaxel every 3 weeks (n=123) or weekly paclitaxel (n=126).

Physician-reported data showed that moderate to severe TIPN occurred in 44% of patients receiving paclitaxel, compared to 25% in those receiving docetaxel. Patients self-reported similar figures—40% for paclitaxel versus 24% for docetaxel. Significantly, dose reductions relating to TIPN occurred more frequently with paclitaxel (28.1%) than with docetaxel (8.5%). Total reductions for all causes were 38.8% for paclitaxel and 24.6% for docetaxel, reinforcing docetaxel’s advantage.

"Our study validates that Black patients with breast cancer are at a much higher risk for chemotherapy-induced peripheral neuropathy," Dr. Ballinger noted. "However, we also discovered that docetaxel caused significantly less neuropathy and fewer dosage reductions than paclitaxel, raising the potential for docetaxel to be a more suitable option for these patients."

While individuals of African ancestry are at increased risk for TIPN, considerable variation exists. The primary goal of the study was to assess genetic predictors of TIPN based on germline DNA. While the trial did not meet its primary endpoint, revealing no differences in neuropathy rates between patients classified as high-risk and low-risk (regardless of the taxane they received), nearly three-quarters of the patients in both groups were categorized as high-risk based on genetic markers.

"We examined two specific genes, SBF2 and FCAMR. While these genes may contribute to TIPN risk, it’s clear that the condition has a multifactorial, multigenic basis. Thus, these genes alone don’t fully explain the risk. There’s still much to learn in predicting TIPN for this population," Dr. Ballinger concluded.

Moving forward, ECOG-ACRIN plans to conduct new trials to further refine taxane-based therapies in Black women with breast cancer. Researchers also aim to build on this trial's successful recruitment strategies for future studies targeting minority populations with limited resources.

"While this particular trial focused on Black patients, the broader takeaway is the need for more personalized cancer therapy to minimize toxicity," Dr. Ballinger emphasized. "Critically, this study serves as a model for how we can thoughtfully design and recruit for trials specifically aimed at underserved communities."

The study was conducted in collaboration with numerous advocacy groups, including Pink-4-Ever Ending Disparities, a nonprofit organization in Indiana focused on closing breast cancer outcome gaps among Black women. The group helped with recruitment through social media platforms like YouTube. Additionally, many patients enrolled in the study did so through the NCI Community Oncology Research Program (NCORP), demonstrating the trial’s success in reaching beyond academic institutions. Notably, this achievement occurred during the challenges of the COVID-19 pandemic, and within a relatively short timeline.

"This trial underscores the effectiveness of designing research specifically for underserved populations. The high level of engagement from Black patients made this study successful," said Dr. Ballinger.

The EAZ171 trial was financially supported by the NCI’s Division of Cancer Prevention and received additional backing from the Susan G. Komen® Foundation and the Vera Bradley Foundation for Breast Cancer.

About ECOG-ACRIN

The ECOG-ACRIN Cancer Research Group is a vast organization composed of nearly 1400 member institutions and 21,000 professionals who develop and conduct cancer research involving adults diagnosed with cancer or at risk. Noted for their advances in precision medicine and biomarker research, ECOG-ACRIN leads major national clinical trials that integrate forward-thinking genomic methodologies. By working with over 40 scientific committees, the organization runs studies that span the full continuum of cancer care, from early detection to treatment of advanced cases. ECOG-ACRIN is primarily supported by funding from the National Cancer Institute, part of the National Institutes of Health. Follow them on Twitter/X @eaonc, Facebook, LinkedIn, Instagram, and YouTube, or contact them at 202-744-4343.

Journal

Journal of Clinical Oncology