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Recent Immunotherapy Treatments for Metastatic Breast Cancer.

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For some cancers such as melanoma and leukemia, immunotherapy has produced responses so durable that there is hope for the possibility of a cure in an increasing proportion of patients. In recent years, these novel therapies have also demonstrated efficacy in battling metastatic breast cancer.

“Breast cancer may not respond as well to immunotherapy compared with other cancers because, in general, breast cancers have a lower tumor mutational burden,” said N. Lynn Henry, MD, PhD, associate professor of internal medicine, Huntsman Cancer Institute, University of Utah, in Salt Lake City. “Tumors with a high mutational burden respond better to immunotherapy.”

According to Mary Disis, MD, director of tumor vaccine medical oncology and medical oncologist at the University of Washington Medicine in Seattle, breast cancer is immunogenic and the disease can stimulate the immune system, just not at the same level as melanoma. Disis noted, “We need to figure out what additional manipulations we need to do to assist breast cancer in stimulating the immune system better.”

The Latest in Immunotherapy

To date, only two immunotherapy drugs have been approved for use in treating triple-negative breast cancer (TNBC): pembrolizumab and atezolizumab. Pembrolizumab was approved specifically for the low percentage of breast cancers that have high levels of microsatellite instability or mismatch repair deficiency. The programmed cell death ligand 1 (PD-L1) inhibitor atezolizumab received US Food and Drug Administration accelerated approval in combination with paclitaxel as treatment for metastatic TNBC that expresses PD-L1 based on a specific companion assay. Atezolizumab is also being tested in combination with other drugs, such as capecitabine or gemcitabine for TNBC.

“In the IMpassion130 clinical trial of patients with untreated ER-, PR-, and HER2-negative metastatic breast cancer, just over 40% of patients were PD-L1– positive, which implies there may be a more substantial proportion of patients who may benefit from immunotherapy regimens than was previously appreciated,” explained Henry. “Based on results available to date, a subset of patients experience durable responses following treatment with immunotherapy regimens, but to a lesser degree compared with that seen with other malignancies, such as melanoma or non–small cell lung cancer.” She also noted that immunotherapy is being used off-label in breast cancer on the basis of anecdotal evidence.

Immune checkpoint inhibitors appear to be more effective in TNBC. In an early-phase trial of pembrolizumab (KEYNOTE-086), patients with ER-, PR-, and HER2- negative breast cancer who were previously untreated had improved response rates with treatment compared with those who had previously received treatment for metastatic disease. “Response rates, however, are still not as high as desired, and many additional trials of combination regimens with immunotherapy plus either chemotherapy or targeted therapies are ongoing,” said Henry.

-GDMeds, an India Pharmacy Service company
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