ONA Interview: Immunotherapy Shows Potential in Several Types of Breast Cancer

The 2019 European Society of Medical Oncology (ESMO) Congress in Barcelona featured some promising studies involving novel combination therapies that may improve outcomes for women with advanced breast cancer. New data presented at the Congress showed that treatment with a CDK4/6 inhibitor plus fulvestrant could help improve overall survival in women with hormone receptor-positive (HR+), HER2– advanced breast cancer. Researchers presented data from 2 studies that included 2 different patient populations and different CDK4/6 inhibitors. The Monarch 2 study evaluated abemaciclib plus fulvestrant in patients with advanced breast cancer after failure of endocrine therapy and regardless of menopausal status.¹ The Monaleesa-3 study investigated ribociclib plus fulvestrant as first- or second-line therapy only in postmenopausal patients.²

New studies also presented at this year’s meeting suggest that immunotherapy may be appropriate for certain subtypes of triple-negative breast cancer. Oncology Nurse Advisor talked to Adam M. Brufsky, MD, PhD, associate chief in the Division of Hematology/Oncology and co-director of the Comprehensive Breast Cancer Center at the University of Pittsburgh School of Medicine, in Pennsylvania, about how immunotherapy is changing the treatment of advanced breast cancer.

Oncology Nurse Advisor (ONA): What were some novel approaches to managing breast cancer discussed at ESMO Congress 2019?

Dr Brufsky: Some of the newer studies had to do with the use of immunotherapy in breast cancer. There was one study in particular that used immunotherapy as part of neoadjuvant therapy added to chemo in early breast cancer. The study shows that immunotherapy potentially improves response rates and hopefully survival. The KEYNOTE-522 study was a phase 3 study looking at pembrolizumab plus chemotherapy vs placebo plus chemo as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early triple-negative breast cancer.³ So, it could potentially improve survival in women who have early stage disease and have triple-negative breast cancer. So, that was one big approach that looked promising.

ONA: In your view, what new approaches may have the greatest impact on breast cancer treatment?

Dr Brufsky: The new approaches that may have a significant impact are the fact that the CDK4 inhibitors, which included palbociclib, ribociclib, and abemaciclib, may be added as a form of therapy for early metastatic breast cancer, and it turns out that when you add them to fulvestrant, you have an improvement in overall survival. So, we knew these agents improved progression-free survival (PFS), but it now looks like they improve overall survival in metastatic breast cancer. We didn’t know that before, and we really have not had a lot of agents that improve overall survival in metastatic breast cancer but now we do.

ONA: In what ways is the management of triple negative breast cancer evolving?

Dr Brufsky: Experts are now saying that we probably should be using immunotherapy for certain subtypes of triple-negative breast cancer. They have identified a particular marker, the PD-L1, on the immune cells in triple negative breast cancer and found that these [patients] will respond to immunotherapy. One abstract that was presented focused on performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer. Research is showing the disease responds to immunotherapy.⁴ We now have a good biomarker for immunotherapy to predict long-term response from these agents.

The KEYNOTE-119 study was a phase 3 study of pembrolizumab vs single-agent chemotherapy for metastatic triple negative breast cancer, and it was a negative study.⁵ These researchers found that immunotherapy did not work. In my opinion, it shows that we probably need to use it early in the course of the disease.

Another interesting study investigated whether trilaciclib improves overall survival when added to gemcitabine/carboplatin for patients with metastatic triple negative breast cancer.⁶ This was a small study and we really are not sure whether trilaciclib is really going to go forward. The investigators really don’t know how it works. They think it is an immunostimulant, but they don’t have a lot of data on it. It is interesting, but it is a small trial and we will just have to what to see where it goes.

A study looking at theprognostic value of tumor infiltrating lymphocytes in patients with early-stage triple negative breast cancers in the absence of chemotherapy was rather interesting. This study sort of tells us what we already knew. If the immune cells are already infiltrating a cancer, then the cancer will respond better to immunotherapy.⁷ It is an interesting study and it shows how this can help with a prognosis in triple-negative breast cancer.

ONA: What effects, if any, are concerns regarding cardiotoxicity having on breast cancer treatment decisions?

Dr Brufsky: This is a great question. In a study looking at radiotherapy-induced cardiovascular mortality in female patients with breast cancer, investigators tried to look at whether radiation therapy on the left side influenced the mortality of women with breast cancer.⁸ So, it is very interesting. We have to figure out does if it matter if the radiation is on just the right side or the left side.

A study that was highlighted at the meeting was a 4-arm randomized, double-blind, controlled trial evaluating the efficacy and safety of cardiotoxicity prevention in patients with nonmetastatic breast cancer treated with anthracyclines with or without trastuzumab.⁹ On this abstract, it is still a little bit early, but what they found was interesting. When combining trastuzumab with an anti-HER2 agent with anthracyclines, you can have a lot of cardiotoxicity. So, in this trial they are trying to decide how to affect that by adding ACE inhibitors and other agents that help heart failure prophylactically. It is an attempt to help prevent heart failure.

A separate preliminary study examined new ways of preventing cardiotoxicity. Investigators looked at the usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab. NT-ProBNP is a marker for heart failure and they are trying to see if it can help us figure out who is going to develop cardiotoxicity on trastuzumab.¹⁰ These are all approaches that have promise, but they are not final yet. It is good that we are trying to delve into what is really going on here exactly and how to prevent it. We clearly don’t want someone to be cured of their breast cancer just to develop heart failure.

ONA: Were any of the presentations you attended surprising in terms of findings/outcomes?

Dr Brufsky: No, not really. The big trial, Keynote 522, was probably the biggest abstract, although its findings did not really surprise anyone. The trial investigated use of immunotherapy for early stage triple-negative breast cancer. The findings showed an improvement in pathological complete response rate. I don’t think we were surprised by that, but that was the biggest abstract. We were also not surprised by the survival data from the CDK4/6 inhibitors in metastatic ER-positive breast cancer. But we were pleasantly surprised that these trials were good news.

References

1. Sledge GW, Toi M, Neven P, et al. MONARCH 2: overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2– advanced breast cancer. Ann Oncol. 2019;30(suppl_5):mdz394.006.

2. Slamon DJ, Neven P, Chia S, et al. Overall survival (OS) results of the phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2–) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Ann Oncol. 2019;30(suppl_5):mdz394.007.

3. Schmid P, Cortés J, Dent R, et al. KEYNOTE-522: phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC). Ann Oncol. 2019;30(suppl_5):mdz394.003.

4. Rugo HS, Loi S, Adams S, et al. Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): post-hoc analysis of IMpassion130. Ann Oncol. 2019;30(suppl_5):mdz394.009.

5. Cortés J, Lipatov O, Im SA, et al. KEYNOTE-119: phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2019;30(suppl_5):mdz394.010.

6. O’Shaughnessy J, Wright GS, Thummala A, et al. Trilaciclib improves overall survival when given with gemcitabine/carboplatin (GC) in patients with metastatic triple negative breast cancer (mTNBC) in a randomized phase II trial. Ann Oncol. 2019;30(suppl_5):mdz394.011.

7. Park JH, Jonas SF, Dieci MV, et al. Prognostic value of tumor infiltrating lymphocytes (TILs) in patients with early-stage triple negative breast cancers (TNBC) in the absence of chemotherapy. Ann Oncol. 2019;30(suppl_5):mdz240.001.

8. De Ridder M, Mulliez T. Estimating radiotherapy-induced cardiovascular mortality in female breast cancer patients. Ann Oncol. 2019;30(suppl_5):mdz240.015.

9. Livi L, Barletta G, Martella F, et al. Pre-specified interim analysis of the SAFE trial (NCT2236806): a 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab. Ann Oncol. 2019;30(suppl_5):mdz240.039.

10. Blancas I, Martín C, Martín-Pérez FJ, et al. Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab. Ann Oncol. 2019;30(suppl_5):mdz240.041.

Take-home points for oncology nurses

• New data reported at the ESMO Congress 2019 suggest that treatment with a CDK4/6 inhibitor plus fulvestrant may help improve overall survival in women with HR+, HER2– advanced breast cancer.

• Immunotherapy may have a place in the early treatment of breast cancer. One study demonstrated that using immunotherapy as part of neoadjuvant therapy added to chemo in early breast cancer may improve response rates and hopefully survival.

• Immunotherapy may be appropriate for certain subtypes of triple-negative breast cancer. A new study suggests that testing for PD-L1 may help identify which patients with triple-negative breast cancer may respond to immunotherapy.

• Biomarkers may help in the prevention of cardiotoxicity in patients with breast cancer. In addition, adding an ACE inhibitor or other agents may help prevent heart failure in patients treated for advanced breast cancer.