Recognizing the need for further evaluation of immunotherapy for breast cancer treatment, Fox Chase Cancer Center has opened two investigator-initiated trials exploring the use of immunotherapy for triple-negative and HER2-positive breast cancer. 

The History of Breast Cancer Immunotherapy

Immunotherapy has changed the treatment landscape of various cancer types, but it was only recently approved for the treatment of certain breast cancers. In March 2019, the U.S. Food and Drug Administration approved atezolizumab plus nab-paclitaxel for first-line treatment of unresectable, locally advanced, and metastatic triple-negative breast cancers that express PD-L1.

While this was a step forward for breast cancer treatment, only a minority of women with metastatic triple-negative breast cancer (considered the most aggressive subtype of the disease) test positive for PD-L1 expression and, at this time, other targeted therapies are not available for this patient population.

“The atezolizumab plus nab-paclitaxel regimen excludes about 60 percent of patients who do not have PD-L1 positive breast cancer or who are ineligible to receive it due to prior treatment,” said Elias Obeid, MD, MPH, Interim Chief of the Division of Breast Medical Oncology at Fox Chase.

Finding Other Options

Women not eligible for the atezolizumab plus nab-paclitaxel regimen may be eligible for enrollment in Fox Chase’s Phase II study, which is investigating another immunotherapy drug (pembrolizumab) in combination with gemcitabine plus carboplatin (a standard chemotherapy combination). To qualify, women must have been diagnosed with metastatic triple-negative breast cancer and have previously received three or less lines of therapy. Patients will be randomly assigned 2:1 to pembrolizumab plus chemotherapy or gemcitabine plus carboplatin alone.

Although gemcitabine plus carboplatin is a standard regimen for the treatment of triple-negative disease, the chemotherapy combination was also chosen specifically in the hope of making tumors more immunogenic, according to Lori J. Goldstein, MD, FASCO, Director of The Naomi and Phil Lippincott Breast Evaluation Center at Fox Chase.

“If we can enhance immune response, we can better harness the body’s immune system and hopefully get responses beyond those seen with either treatment alone,” Goldstein said.

Unlike the atezolizumab plus nab-paclitaxel regimen, this trial has no requirement for PD-L1 expression, and all patients assigned to the chemotherapy-only arm will be eligible for treatment with immunotherapy if they experience disease progression.

Obeid and Goldstein are also recruiting women with metastatic HER2-positive breast cancer for a first-of-its-kind immunotherapy trial exploring the use of first-line atezolizumab combined with paclitaxel, trastuzumab, and pertuzumab. There is no eligibility requirement for tumor PD-L1 expression and, unlike a similar randomized national cooperative group trial, the Phase II study will provide all participants with exposure to the immunotherapy drug.

Fox Chase researchers will collect both tissue and blood specimens from patients enrolled in both the HER2-positive breast cancer and triple-negative breast cancer trials in order to potentially identify biomarkers for response.

“In the last 25 years, there has been at least a 30 percent improvement in breast cancer survival, and that is because of controlled clinical trials,” said Goldstein. “We are better able to choose appropriate treatments for each patient because of the results of previous studies, and this will be the case with our current trials.”

What You Should Know About Immunotherapy Trials for Triple-Negative and HER2-Positive Breast Cancer

• While the approval of atezolizumab plus nab-paclitaxel for first-line treatment of unresectable, locally advanced and metastatic triple-negative breast cancers that express PD-L1 in 2019 was a major step forward for breast cancer treatment, it excludes a majority of breast cancer patients (approximately 60 percent).
• To better evaluate the use of immunotherapy for the treatment of triple-negative and HER2-positive breast cancer, Fox Chase Cancer Center is now offering two investigator-initiated trials that give all participants access to the immunotherapy (even if they start on a chemotherapy-only arm).
• Fox Chase researchers will collect both tissue and blood specimens from patients enrolled in both the HER2-positive breast cancer and triple-negative breast cancer trials in order to potentially identify biomarkers for response.