Aggressive breast cancer combination therapy trial provides results by race

Immunologically active proteins on a T cell. TCR (blue), CD-4 (light blue), CD-28 (dark blue), PD-1 (magenta), CTLA-4 (purple), Ca channel (dark purple). T cell receptor, CD-4 and CD-28 activate T cells, while PD-1 and CTLA-4 inhibit T cell activation. [selvanegra/GEtty Images]

New immunotherapy treatments show promise for an aggressive and hard-to-treat form of breast cancer called triple-negative breast cancer, but not everyone has the same access to treatment. Triple-negative breast cancer accounts for about 15% of all breast cancers in the general population, but in African-American women, that number can be as high as 40-50%. Despite carrying a much greater disease burden, African Americans remain severely underrepresented in clinical trials, in some cases representing only 4% of the cohort population.

But now researchers at the Yale Cancer Center have taken the first step to correcting that. In research published July 29 in the journal Clinical cancer research, a large immunotherapy trial examining the efficacy of durvalumab in combination with neoadjuvant chemotherapy for stage I-III triple-negative breast cancer has reopened the recruitment of African-American women. They extended the trial recruitment so that the patient cohort was representative of the population. The study, which ended up accumulating enough patients for African Americans to make up 31% of the cohort, found there was no difference in the overall three-year survival rate or survival rate. without event by breed.

“By excluding a population from the studies, we don’t really learn about the efficacy and toxicity of a particular drug in that group.” said Lajos Pusztai, professor of medicine at the Yale School of Medicine and lead author of the study. “By employing a very simple set of administrative measures, we made the clinical trial representative of the population,” he said.

Triple negative breast cancer is a very aggressive form of breast cancer that is more likely to spread and recur. Cancer lacks hormone receptors that respond well to targeted therapies, which has traditionally left patients with limited treatment options. Typically, patients had to rely on chemotherapy alone, and survival rates hovered around 70%. But new immunotherapies have changed the outlook for patients with this devastating type of breast cancer.

In a previously published clinical trial, Pusztai and his team showed that the checkpoint inhibitor durvalumab, used in combination with chemotherapy before surgery, was beneficial for patients with non-metastatic triple-negative breast cancer. . Other trials have also shown similar results. The KEYNOTE-522 trial, for example, which evaluated the immunotherapeutic drug pembrolizumab plus chemotherapy, increased the 3-year event-free survival rate to 84.5% compared to 76.8% with chemotherapy alone.

But Pusztai’s initial trial did not enroll patients who reflected the racial and ethnic makeup of the surrounding New Haven, Connecticut, neighborhood or the population with the highest disease burden. To better understand how this treatment benefits African Americans, Pusztai and his colleagues created an extension cohort to enroll more patients. They recruited 67 additional patients, 21 of whom identified as black (31% of the total cohort).

The researchers found that there were no statistically significant differences between African American and non-African American patients in pathologic complete response rates, which were 43 versus 48 percent, respectively. Additionally, there were no significant differences between metastatic recurrence rates, which were 14% in African American patients and 17% in non-African American patients.

Pusztai said he was not surprised by the results. “I think when people get the same treatment in the same way, their results are very similar.” He believes that the marginalization of groups, rather than biology, is to blame for the disparities in this type of cancer. He hopes that in the future, clinical trials will mandate the recruitment of patients representative of the population. This will not only ensure the effectiveness of treatments in different racial and ethnic groups, but will also improve equity and access to better cancer drugs.

“All groups deserve the opportunity to receive tomorrow’s therapies today,” he said.

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