Neoadjuvant immunotherapy effective regardless of race in triple-negative breast cancer
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Results of a phase 1/phase 2 study showed similar treatment outcomes among Black and non-Black women who received durvalumab plus chemotherapy prior to surgery for triple-negative breast cancer.
Data published in Clinical Cancer Research revealed no statistically significant differences in efficacy outcomes according to race and no additional treatment-related adverse events.
The results suggest racial disparities can be addressed if Black patients are provided similar treatment and follow-up care, the investigators noted.
Background
The goals of promoting more accurate representation of diverse racial and ethnic populations in clinical trials include gaining insight into potential biological differences in how patients metabolize or develop treatment-related adverse effects to novel therapies, as well as preventing social injustice, according to Lajos Pusztai, MD, DPhil, professor of medicine at Yale School of Medicine and scientific co-director of Center for Breast Cancer at Yale Cancer Center.
“Every clinical trial has the potential to provide patients with tomorrow's therapies today," he told Healio. "Because novel therapies often become part of the standard of care, we should ensure that we are offering these therapies to everyone equally.”
Methodology
Pusztai and colleagues conducted a single center cohort extension study that enrolled 67 women (mean age, 51 years; range, 27–79) with the aim of assessing the efficacy of neoadjuvant immunotherapy with durvalumab (Imfinzi, AstraZeneca) — a PD-L1 checkpoint inhibitor — among a larger sample of Black patients.
A total of 21 patients in the extension cohort self-identified as African-American.
The investigators accomplished this by mandating that 30% of the extension cohort comprised Black patients to match their proportion among the local population in New Haven, Connecticut, Pusztai noted.
"We had to closely study accrual after a set number of non-African American patients and kept the study open for the African American population,” he said.
Four patients received treatment during the phase 1 portion that included durvalumab dosed at 3 mg/kg once weekly as part of a neoadjuvant treatment regimen. The remaining 63 patients received the phase 2 durvalumab dose of 10 mg/kg every 2 weeks.
Pathologic complete response rate among patients who received the phase 2 dose served as the study’s primary efficacy endpoint. Secondary endpoints included OS, EFS and safety.
The study had a median follow-up of 35 months (range, 25-70).
Key findings
Researchers found no significant association between race and pathologic complete response rates. Thirty-one patients (46%; 95% CI, 34–58) in the intention-to-treat population had a pathologic complete response to therapy, including 43% of Black patients and 48% of the non-Black patients.
The two groups had similar cancer recurrence rates — 14% of Black patients developed distant metastatic recurrence compared with 17% of non-Black patients.
Investigators reported a 3-year OS rate of 85% (95% CI, 74–93) for the entire study population, including 81% (95% CI, 58–95) among Black patients and 87% (95% CI, 74–95) among non-Black patients (HR = 1.72; 95% CI, 0.48–6.13).
The two groups also had similar estimated 3-year EFS rates: 78.3% (95% CI, 64-89) among non-Black patients and 71.4% (95% CI, 48–89) among Black patients (HR = 1.451; 95% CI, 0.524–4.017).
Patients who achieved an initial pathologic complete response to therapy had significantly longer survival compared with those who did not.
Researchers reported a 3-year OS rate of 96.8% for patients who had a pathologic complete response compared with 81.8% for those who did not. Similarly, patients who had a pathologic complete response to therapy had a higher 3-year EFS rate (90.3% vs. 66.7%).
Clinical implications
Pusztai said there are two major takeaways from the results of his group's study.
“When people are treated in the same way and given similar follow-up care, then treatment outcomes are similar regardless of ancestry, race or socioeconomic status,” he told Healio. “Secondly, enforcing proportional representation in a clinical trial is achievable.”
The extension study’s mandate to enroll a certain proportion of Black patients was successful, but at a cost, Pusztai noted. The non-Black cohort completed the study about a year earlier than the Black cohort due to differences in accrual rates.
“That’s a problem,” Pusztai said. “Our next challenge is to work on how we can improve the accrual rate so that all types of ancestry groups are enrolled in studies at a similar rate.”
Pusztai said delaying the results for the single-center study he and his colleagues performed was acceptable, but for larger, randomized, multicenter studies that can impact the standard of care for a disease, delays to ensure proportional racial and ethnic participation would lead to additional costs. In addition, he said delaying a final analysis could result in additional deaths if information about a potentially life-extending therapy is not disseminated promptly.
For more information:
Lajos Pusztai, MD, DPhil, can be reached at Yale Cancer Center, 333 Cedar St., P.O. Box 208032, New Haven, CT 06520; email: lajos.pusztai@yale.edu.
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Foldi J, et al. Clin Cancer Res. 2022;doi:10.1158/1078-0432.CCR-22-0862.
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