Strategies to Improve Treatment

The development of more effective treatment for TNBC requires that new and innovative therapies be evaluated with cancer patients. Patients may gain access to better treatments by participating in a clinical trial, and participation in a clinical trial also contributes to the cancer community’s understanding of optimal cancer care and may lead to better standard treatments. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. There are several areas of active investigation aimed at improving the treatment of TNBC and include some of the following:

Strategies To Improve The Treatment of Early Stage TNBC

Radiation After Lumpectomy Improves Outcomes Among Elderly:  The addition of radiation therapy following a lumpectomy appears to significantly improve outcomes among elderly women with triple-negative breast cancer. Standard treatment for TNBC typically consists of surgery, chemotherapy and/or radiation therapy. Elderly patients, however, are often not offered the most aggressive treatment regimens, despite studies demonstrating a clear benefit with an aggressive treatment strategy. This is commonly due to the perception that elderly patients might not be able to tolerate the aggressive treatment as well as their younger counterparts.

Researchers recently evaluated data exploring the use of radiation following a lumpectomy among women over 70 with early-stage TNBC. Overall survival was approximately 98% for patients who received radiation following their lumpectomy, compared to approximately 86% for patients treated with a lumpectomy only and death from breast cancer occurred in only 1% of patients treated with the addition of radiation, compared to 6% of patients treated with lumpectomy only.3

Neoadjuvant Carboplatin Adding carboplatin to pre-surgery chemotherapy improved disease-free survival for patients with TNBC

Chemotherapy administered before surgery with the goal of reducing the size of the cancer for surgical removal is called neoadjuvant chemotherapy. Previously reported clinical study results have suggested that adding carboplatin to anthracycline/taxane-based neoadjuvant chemotherapy can increase the proportion of patients with TNBC who had attained a pathologic complete response [pCR], from 36.9 percent to 53.2 percent.

In the currently reported study researchers enrolled 315 patients with TNBC to receive 18 weeks of neoadjuvant chemotherapy consisting of paclitaxel, non-pegylated-liposomal doxorubicin, and bevacizumab and were randomly assigned to concurrently receive weekly carboplatin or nothing extra and then directly compared.

After a median follow-up of three years, 85.5 percent of TNBC patients treated with the additional carboplatin survived without evidence of cancer recurrence compared to only 76.1 percent of patients treated with paclitaxel, non-pegylated-liposomal doxorubicin, bevacizumab, and no carboplatin.4

PD-1 Checkpoint Inhibitors The cancer immunotherapy strategy known as programmed cell death 1 (PD-1) has generated great excitement for its ability to help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 are called checkpoint inhibitors and may enhance the ability of the immune system to fight cancer.

Keytruda is a fully humanized monoclonal antibody that binds with high-affinity to the PD-1 receptor. In a phase 1 study, 32 heavily pretreated patients with recurrent or metastatic TNBC positive for PD-1 were administered Keytruda every 2 weeks until they had either a complete response, partial or stable response, or confirmed disease progression.  Overall, 18.5% of patients responded to treatment with Keytruda. Keytruda has anti-cancer activity in this hard-to-treat group with advanced triple-negative breast cancer.5

Sacituzumab Govitecan  (IMMU-132) is referred to as an antibody-conjugate, and is still in investigative stages. It is comprised of an antibody that attaches to specific receptors called Trop-2 receptors. The antibody is attached to a drug that kills cancer cells, called SN-38.

Trop-2 receptors are often found in large numbers on the surface of cancer cells, but not healthy cells. Once IMMU-132 binds to the Trop-2 receptors, it delivers SN-38 into the cancer cell. This kills the cancer cell, while only affecting a small portion of healthy cells. By targeting Trop-2 receptors, larger amounts of chemotherapy can be delivered to the cancer cells because healthy cells are largely spared from the cancer-killing effects of the treatment.

A recent clinical trial was conducted to further evaluate the effectiveness of IMMU-132 in patients with TNBC. The trial included patients with TMBC that had spread to distant sites in their body, and had received a median of 5 prior therapies. Final results from the trial are awaited to fully determine patient outcomes. Meanwhile, patient enrollment for continuing larger comparative trials with IMMU-132 in TNBC is ongoing.6

Atezolizumab is an agent referred to as a checkpoint inhibitor. It helps the immune system recognize cancer cells as a threat, so that an immune attack is initiated against the cancer.  Researchers have reported the results of a clinical trial evaluating the combination consisting of a azetolizumab, and Abraxane in women with advanced TNBC.  Overall anti-cancer responses were achieved in 70.8% of patients.7

References

1 Excerpt from Women Magazine: By Bhuvaneswari Ramaswamy MD, MRCP, Assistant Professor of Internal Medicine, Division of Medical Oncology, Arthur G. James Cancer Hospital andRichard J. Solove Research Institute
The Ohio State University.

2 Women Magazine http://awomanshealth.com/

3 Szeja S, Hatch S. Outcomes associated with adjuvant radiation after lumpectomy for elderly women with T1-2N0M0 triple-negative breast cancer: SEER analysis. Journal of Clinical Oncology. 2015; 33 (sup 28S; abstr 39).

4 von Minckwitz G, Loibl S, Schneeweiss A, et al. Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). Abstract: S2-04. Presented at the 2015 San Antonio Breast Cancer Symposium, San Antonio, TX. December 9, 2015.

5 Nanda R, Chow LQ, Dees EC, et al. A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Presented at the 2014 San Antonio Breast Cancer Symposium, December 9-13, 2014. San Antonio, Texas. Abstract S1-09.

6 Immunomedics, Inc. Press Release. U.S. Food and Drug Adminstration (FDA) Grants Breakthrough Therapy Designation to Immunomedics for Sacituzumab Govitecan for the Treatment of Patients with Triple-Negative Breast Cancer. . Available at: http://www.immunomedics.com/news-2016.shtml. Accessed February 8, 2016

7 Reference: Adams S, et al. Safety and clinical activity of atezolizumab (anti-PD-L1) in combination with nab-paclitaxel in patients with triple-negative breast cancer. Proceedings from the 2015 annual San Antonio Breast Cancer Symposium. Presented December 10, 2015. Abstract number: 850477.