Sylvia Adams, MD, professor in the Department of Medicine at NYU Grossman School of Medicine and director of the Breast Cancer Center of NYU Langone’s Perlmutter Cancer Center, discusses the utility of combining anti–CTLA-4 and anti–PD-1 agents in breast cancer. 

CTLA-4 inhibitors can elicit a T-cell immune response that is further stimulated by PD-1/PD-L1 inhibitors, explains Adams. 

PD-L1 inhibitors have demonstrated utility when combined with chemotherapy in the breast cancer setting, says Adams. For example, in March 2019, atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) was granted accelerated approval by the FDA for the treatment of patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer. 

Conversely, CTLA-4 inhibitors have not elicited the same benefit in breast cancer and it is known that these agents are associated with significant toxicity, explains Adams. As such, these agents are typically reserved for use in the clinical trial setting, for patients who have not responded to standard therapies and have a poor prognosis. 

Notably, the combination of CTLA-4 and PD-1 blockade has demonstrated success in melanoma and lung cancer. Based on this promise, this approach has recently been evaluated in a rare breast cancer subtype called metaplastic breast cancer. Results from the 

 showed early clinical activity with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) in this patient population, concludes Adams.

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Sylvia Adams, MD, discusses the utility of combining anti–CTLA-4 and anti–PD-1 agents in breast cancer. 



Dr. Adams on the Utility of Combination CTLA-4 and PD-1 Blockade in Breast Cancer

Sylvia Adams, MD, associate professor, Department of Medicine, director, Clinical Research, Breast Cancer Disease Management Group, NYU Langone’s Perlmutter Cancer Center, discusses whether the number of prior lines of therapy impact response to immunotherapy in patients with triple-negative breast cancer (TNBC).

The number of prior lines of therapy a patient has been exposed to is important, explains Adams. Patients who have had prior therapies in the metastatic setting have significantly lower response rates than patients being treated in the frontline. In the palliative setting, response rates can be as low as 5% or 10% in women who have had prior chemotherapy, notes Adams.

However, patients who are treated in the frontline setting when they are diagnosed with metastatic recurrence can show response rates as high as 25%. Because of this, patients should be enrolled in clinical trials as early as possible.

Presently, most trials are targeting the known subtypes of breast cancer. Ideally, they should focus on the subsets of TNBC that have an immune infiltrate at diagnosis or at the start of treatment, says Adams, as those are the patients who are more likely to respond to immunotherapy.

Dr. Adams on Whether Prior Lines of Therapy Impact Response to Immunotherapy in TNBC

Sylvia Adams, MD, associate professor, Department of Medicine, director, Clinical Research, Breast Cancer Disease Management Group, NYU Langone’s Perlmutter Cancer Center, discusses combinatorial approaches in triple-negative breast cancer (TNBC).

Physicians have been looking at immunotherapy combinations with chemotherapy because chemotherapy is the main standard of care for these women, explains Adams. These drugs can stimulate immune response and keep women stable until the immune medications work. In a phase Ib trial with 32 women, about one-half of the patients had a response to treatment in the first-line setting. Many women are alive at 1 and 2 years, which is not that common with standard chemotherapies, says Adams.

Physicians still have to further evaluate biomarkers. Adams hopes that there will be trials with an emphasis on tissue-based correlative studies, so physicians can figure out which patients respond and be able to predict that response in advance. For the other patients, physicians have to figure out other targets. Adams notes that T cells do not only have PD-1/PD-L1 as targets, they can have many others such as TIM-3 or LAG-3. Those are important to target as well, explains Adams.

Sylvia Adams, MD, associate professor, Department of Medicine, director, Clinical Research, Breast Cancer Disease Management Group, NYU Langone’s Perlmutter Cancer Center, discusses combinatorial approaches in triple-negative breast cancer.

Dr. Adams on Combinatorial Approaches in Triple-Negative Breast Cancer

Sylvia Adams, MD, associate professor, Department of Medicine, director, Clinical Research, Breast Cancer Disease Management Group, New York University Langone’s Perlmutter Cancer Center, discusses immunotherapy in triple-negative breast cancer (TNBC).

Immunotherapy is a very exciting research area, especially for women with TNBC, says Adams. It has been shown that TNBC is visible to the immune system. At diagnosis, there are some tumors that have already been infiltrated with immune cells. TNBC shows immunogenicity, says Adams and harnessing the immune response—either in combination or alone&mdash;can make a big difference in patient outcomes.

The drugs that are currently being tested are agents that target the inhibitor receptors on immune cells. Inhibiting a negative signal can activate an immune response that targets the cancer, says Adams. This has been shown to induce durable responses in a subset of women with metastatic disease. Since this does not work in a majority of patients, Adams states that it is important to define the women who will benefit from the treatment and the women who may benefit from combinatorial approaches.

Sylvia Adams, MD

Articles

Dr. Adams on the Utility of Combination CTLA-4 and PD-1 Blockade in Breast Cancer

Dr. Adams on Whether Prior Lines of Therapy Impact Response to Immunotherapy in TNBC

Dr. Adams on Combinatorial Approaches in Triple-Negative Breast Cancer

Dr. Adams on Immunotherapy in Triple-Negative Breast Cancer