Breast Cancer Breakthrough — Immunotherapy C...
Breast Cancer
Breast Cancer Breakthrough — Immunotherapy Combination Shows Major Boost in Survival Rates
Published Oct 20, 2018
In an important advance, immunotherapy has been shown for the first time to extend the lives of patients with a really dangerous form of breast cancer. In a worldwide study of over 900 women, patients given immunotherapy plus chemotherapy lived 9 1/2 months longer than those given chemotherapy alone. Leading experts in breast cancer say doctors will now treat patients with triple negative breast cancer with immunotherapy plus chemotherapy.
“Unquestionably practice changing,” said noted oncologist Dr. Larry Norton, Medical Director of Evelyn H. Lauder Breast Center at Memorial Sloan-Kettering Cancer Center.
Related: The Promise of Immunotherapy for Cancer Treatment
There is additional excitement over what this means for all patients with breast cancer.
“I think this does open the door to immunotherapy for breast cancer,” said Dr. Harold Burstein, of the Dana Farber Cancer Institute.
The study was presented at the major European cancer meeting in Munich and simultaneously published in the New England Journal of Medicine.
The study is particularly significant because for many years it was believed that most breast cancers would not respond to immunotherapy. Dr. Sylvia Adams, of NYU Langone Cancer Center, and a study author, said in an interview with SurvivorNet the belief was that “breast tumors were not infiltrated much by the immune cells of the patient.” But Dr. Adams says research at NYU five years ago demonstrated that this belief was a mistake. In patients with a particularly dangerous form of breast cancer there were immune responses seen in the tumor. That finding lead to the theory that “if we harnessed the immune system even more, we can improve outcomes in patients,” Dr. Adams said.
The dangerous form of breast cancer that is the target for this immunotherapy study is triple negative breast cancer that has spread beyond the breast and lymph nodes.
When breast cancer is diagnosed, the cells in the tumor are analyzed for receptors which are like flags on the outside of the cancer cell. These receptors signal what the cancer cell needs to grow. If the cells lack estrogen receptors, progesterone receptors, and HER2 receptors, it is called triple negative breast cancer. That creates a problem for treatment. If the growth of the cancer is not supported by hormones or HER2, then drugs to target the hormones (like tamoxifen or aromatase inhibitors), or the HER2 receptor (like Herceptin) won’t be effective.
What is triple negative breast cancer?
“Metastatic triple negative breast cancer lacks a targeted treatment. It is often the most virulent breast cancer and there is a clear need for better treatment,” Dr. Burstein said.
This lack of effective treatment is why women diagnosed with metastatic triple negative breast cancer usually only survive for 12 to 18 months. If the cancer has not metastasized in a triple negative patient, the majority can be cured with surgery, chemotherapy, and radiation. But still, over 25% of non-metastatic patients will relapse and have a poor prognosis.
Based on the theory that breast tumors in triple negative patients would respond to immunotherapy, and the critical need for new treatments in these patients, a study called IMpassion 130 was launched at 41 centers around the country. In the U.S., in addition to NYU, participating centers included Dana Farber Cancer Institute, Bloomberg – Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, and University of California San Francisco.
When the researchers set up the study they made it clear that they not only wanted to see the effectiveness of immunotherapy in patients with advanced triple negative breast cancer, but they set up as an additional goal for results in a subgroup of patients whose tumors were positive for a protein called PD-L1. This protein is a problem because it helps keep T-cells from killing cancer cells. Immunotherapy blocks PD-L1 allowing the T-cells to attack the cancer.
Half of women with advanced triple negative breast cancer were given the immunotherapy drug atezolizumab plus chemotherapy. The other half were given only chemotherapy. After a follow-up of a little over a year the benefit of immunotherapy was significant, particularly in the 41% of patients positive for PD-L1. They looked at both how long patients were free of cancer, known as progression free survival, and the overall survival.
- Immunotherapy plus chemotherapy – 7.2 months of progression free survival
- Chemotherapy – 5.5 months progression free survival
- Immunotherapy plus chemotherapy – 21.3 months of overall survival
- Chemotherapy – 17.6 months overall survival
But in the patients positive for PD-L1 the results were much better. Instead of living four months longer, those patients lived 9 1/2 months longer. Dr. Adams said these results are really exciting. “The trial showed for very first time that immunotherapy can help women when added to chemotherapy with metastatic triple negative breast cancer. It’s a big step forward because compared to standard therapy we are now able to have women experience longer periods of stability of their cancer, even potential cures,” she said.
Dr. Adams is particularly encouraged by the results because of the kind of women who get triple negative breast cancer. “We see typically 30-40 year old women with young children and for them to have one or two years more of life is truly important.” Dr. Adams believes that the study will change practice and she expects it to lead to FDA approval.
Dr. Burstein agrees. “The survival benefit is nearly 10 months so I think that’s a sufficiently robust benefit that clinicians are going to treat people this way and patients would want to be treated.”
Immunotherapy is now expected to become the first-line treatment for patients with metastatic triple negative breast cancer. And, Dr. Burstein said, “we are going to have to start testing all triple negative breast cancer patients for PD-L1.”
Looking ahead, Dr. Norton sees an important impact of the study. He said some patients in the study did exceptionally well. Some patients treated with immunotherapy were disease-free for as long as three years. Dr. Norton says we need to find out why by analyzing the tumors of those exceptional patients. “What is it about the tumors that cause the patients to do extraordinarily well. Is it something about the cancer or something about the patient’s own immune system.”
Getting answers to those questions could lead to advances in treatments not just for patients with triple negative breast cancer, but for all breast cancer patients.
Learn more about SurvivorNet's rigorous medical review process.
In an important advance, immunotherapy has been shown for the first time to extend the lives of patients with a really dangerous form of breast cancer. In a worldwide study of over 900 women, patients given immunotherapy plus chemotherapy lived 9 1/2 months longer than those given chemotherapy alone. Leading experts in breast cancer say doctors will now treat patients with triple negative breast cancer with immunotherapy plus chemotherapy.
“Unquestionably practice changing,” said noted oncologist Dr. Larry Norton, Medical Director of Evelyn H. Lauder Breast Center at Memorial Sloan-Kettering Cancer Center.
Related: The Promise of Immunotherapy for Cancer Treatment
There is additional excitement over what this means for all patients with breast cancer.
“I think this does open the door to immunotherapy for breast cancer,” said Dr. Harold Burstein, of the Dana Farber Cancer Institute.
The study was presented at the major European cancer meeting in Munich and simultaneously published in the New England Journal of Medicine.
The study is particularly significant because for many years it was believed that most breast cancers would not respond to immunotherapy. Dr. Sylvia Adams, of NYU Langone Cancer Center, and a study author, said in an interview with SurvivorNet the belief was that “breast tumors were not infiltrated much by the immune cells of the patient.” But Dr. Adams says research at NYU five years ago demonstrated that this belief was a mistake. In patients with a particularly dangerous form of breast cancer there were immune responses seen in the tumor. That finding lead to the theory that “if we harnessed the immune system even more, we can improve outcomes in patients,” Dr. Adams said.
The dangerous form of breast cancer that is the target for this immunotherapy study is triple negative breast cancer that has spread beyond the breast and lymph nodes.
When breast cancer is diagnosed, the cells in the tumor are analyzed for receptors which are like flags on the outside of the cancer cell. These receptors signal what the cancer cell needs to grow. If the cells lack estrogen receptors, progesterone receptors, and HER2 receptors, it is called triple negative breast cancer. That creates a problem for treatment. If the growth of the cancer is not supported by hormones or HER2, then drugs to target the hormones (like tamoxifen or aromatase inhibitors), or the HER2 receptor (like Herceptin) won’t be effective.
What is triple negative breast cancer?
“Metastatic triple negative breast cancer lacks a targeted treatment. It is often the most virulent breast cancer and there is a clear need for better treatment,” Dr. Burstein said.
This lack of effective treatment is why women diagnosed with metastatic triple negative breast cancer usually only survive for 12 to 18 months. If the cancer has not metastasized in a triple negative patient, the majority can be cured with surgery, chemotherapy, and radiation. But still, over 25% of non-metastatic patients will relapse and have a poor prognosis.
Based on the theory that breast tumors in triple negative patients would respond to immunotherapy, and the critical need for new treatments in these patients, a study called IMpassion 130 was launched at 41 centers around the country. In the U.S., in addition to NYU, participating centers included Dana Farber Cancer Institute, Bloomberg – Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, and University of California San Francisco.
When the researchers set up the study they made it clear that they not only wanted to see the effectiveness of immunotherapy in patients with advanced triple negative breast cancer, but they set up as an additional goal for results in a subgroup of patients whose tumors were positive for a protein called PD-L1. This protein is a problem because it helps keep T-cells from killing cancer cells. Immunotherapy blocks PD-L1 allowing the T-cells to attack the cancer.
Half of women with advanced triple negative breast cancer were given the immunotherapy drug atezolizumab plus chemotherapy. The other half were given only chemotherapy. After a follow-up of a little over a year the benefit of immunotherapy was significant, particularly in the 41% of patients positive for PD-L1. They looked at both how long patients were free of cancer, known as progression free survival, and the overall survival.
- Immunotherapy plus chemotherapy – 7.2 months of progression free survival
- Chemotherapy – 5.5 months progression free survival
- Immunotherapy plus chemotherapy – 21.3 months of overall survival
- Chemotherapy – 17.6 months overall survival
But in the patients positive for PD-L1 the results were much better. Instead of living four months longer, those patients lived 9 1/2 months longer. Dr. Adams said these results are really exciting. “The trial showed for very first time that immunotherapy can help women when added to chemotherapy with metastatic triple negative breast cancer. It’s a big step forward because compared to standard therapy we are now able to have women experience longer periods of stability of their cancer, even potential cures,” she said.
Dr. Adams is particularly encouraged by the results because of the kind of women who get triple negative breast cancer. “We see typically 30-40 year old women with young children and for them to have one or two years more of life is truly important.” Dr. Adams believes that the study will change practice and she expects it to lead to FDA approval.
Dr. Burstein agrees. “The survival benefit is nearly 10 months so I think that’s a sufficiently robust benefit that clinicians are going to treat people this way and patients would want to be treated.”
Immunotherapy is now expected to become the first-line treatment for patients with metastatic triple negative breast cancer. And, Dr. Burstein said, “we are going to have to start testing all triple negative breast cancer patients for PD-L1.”
Looking ahead, Dr. Norton sees an important impact of the study. He said some patients in the study did exceptionally well. Some patients treated with immunotherapy were disease-free for as long as three years. Dr. Norton says we need to find out why by analyzing the tumors of those exceptional patients. “What is it about the tumors that cause the patients to do extraordinarily well. Is it something about the cancer or something about the patient’s own immune system.”
Getting answers to those questions could lead to advances in treatments not just for patients with triple negative breast cancer, but for all breast cancer patients.
Learn more about SurvivorNet's rigorous medical review process.