The 2021 San Antonio Breast Cancer Symposium was held last month and, as always, I looked forward to attending and learning about progress in breast cancer research. The Symposium was a hybrid event this time, with some attendees participating in person and many others participating virtually, as I did.
This was not a year with major headline stories to report but I did learn a lot. One major area of focus this year was immunotherapy, with a number of different sessions providing updates on clinical trials and reviewing where things stand now with the use of immunotherapy in treating breast cancer.
Immunotherapy drugs in general work by stimulating a patient’s own immune system to fight cancer. Immunotherapy has come to be viewed as a fourth pillar of cancer treatment, along with surgery, chemotherapy and radiation. But it’s use in breast cancer has been limited so far.
Sometimes cancer cells are able to evade the immune system by taking advantage of certain safeguards that prevent our immune system from attacking normal cells. Immunotherapy drugs called checkpoint inhibitors work by “releasing the brakes” on the immune system so that it can identify and attack the cancer cells. This is the area of immunotherapy where new treatments have begun to be approved in breast cancer.
Immunotherapy in Metastatic Triple Negative Breast Cancer
In breast cancer, checkpoint inhibitors were first approved as part of treatment for metastatic disease.
The first FDA approval of a checkpoint inhibitor in treatment of metastatic triple negative breast cancer came in 2019 for the drug Tecentriq (atezolizumab). And in 2020, the FDA approved a second checkpoint inhibitor, Keytruda (pembrolizumab) in metastatic TNBC treatment. I wrote about the approvals of the two new therapies in this post.
In both cases, the immunotherapy drug is given in combination with chemotherapy and is for patients whose tumors express the biomarker, PD-L1. (Currently, Keytruda is the only approved checkpoint inhibitor in the United States, after the maker of Tecentriq withdrew the breast cancer indication for this medication last year.)
Which metastatic TNBC patients benefit from Keytruda? Dr. Javier Cortes presented an analysis of the results from Keynote-355, the clinical trial on which the FDA’s approval was based. The analysis showed that the patients who benefited were those whose tumors expressed high levels of the biomarker PD-L1.
So how can more benefit? This question was addressed in a presentation by Dr. Hope Rugo. Dr. Rugo noted that only about 38% of the patients in the trial benefitted from Keytruda. She said that we need to find ways to amplify the immune response so that it can benefit those whose tumors don’t have high levels of PD-L1.
She mentioned several possible ways to do that. These included using chemotherapy to induce a greater immune response, combining checkpoint inhibitors with other drugs that stimulate the immune system, and combining checkpoint inhibitors with targeted therapies or radiation treatment. There are various studies underway to investigate these approaches.
Dr. Rugo also stressed what she referred to as the “patient cost of therapy”–the toxicity of treatment. She noted that the combination of checkpoint inhibitors with chemotherapy increases toxicity. This leads to questions such as whether the chemotherapy part of the regimen can eventually be discontinued for those who do well.
Immunotherapy in Early Stage Triple Negative Breast Cancer
In 2021, Keytruda received another important approval from the FDA. This time, approval was extended to treatment of early stage (stages 2 and 3) TNBC that expresses high levels of the biomarker PD-L1.
In a presentation on immunotherapy in early stage TNBC, Dr. Heather Mcarthur noted that Keytruda has become “standard of care”, but that there are lots of questions. Questions include how to reduce toxicity, understanding the impact of immunotherapy on fertility since many TNBC patients are young, and how to make the therapy work for more patients.
The Keytruda regimen involves a lot of toxicity since it includes not just one chemotherapy drug, but four. Yes, there are four chemotherapy drugs in the approved regimen for each patient.
Dr. Mcarthur noted that some of these drugs may not be necessary for some groups of patients and that various clinical trials are ongoing to explore this. She also questioned whether the “layering of therapies”, the traditional approach in cancer medicine, is the still the way to go with immunotherapy.
Can Immunotherapy Help in Other Breast Cancer Subtypes?
Breast cancer has many variations and, in some cases, HER2-positive or hormone receptor-positive breast cancer also express high levels of PD-L1, suggesting that checkpoint inhibitors may be beneficial.
Additional clinical trials are exploring whether immunotherapy can help in these subtypes.
So, to recap, there are immunotherapies approved and in use now for triple negative breast cancer–both metastatic and early stage.
My biggest takeaway was that there are lots of clinical trials underway exploring such critical questions as finding ways to make these therapies work for more people, in triple negative breast cancer and other subtypes too, and figuring out how to reduce toxicities.
While not mentioned in these talks, immunotherapies are extremely expensive. We also need to address the financial toxicities of cancer treatment. I’ve written about financial toxicity in this post.
Hopefully, there will be information in the near future from some of the ongoing clinical trials that can open up immunotherapy as a treatment option for more people with breast cancer who could benefit.
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