American Society of Clinical Oncology 2017

This year, more than 40,000 people attended the 2017 ASCO meeting from June 2-6 in Chicago. No matter how many times I attend this meeting, I am impressed, almost overwhelmed by the reality of being surrounded by physicians, scientists and advocates from every corner of the world who come together to share their work, their ideas and their aspirations for improving our understanding and care for people with cancer. There is real progress in so many areas for so many different types of cancer, progress which stems from the ever deepening understanding of how cells grow both normally and abnormally when they become cancerous. This impossibly complex and multi-layered world is opening the door, one step at a time, to increasingly precise therapies.

There is another very real change occurring as well. While people have talked for many years about “the patient voice,” it is now clear that patient involvement, the patient experience, patient reported outcomes and the actual patient voice are becoming integral to every aspect of caring for and treating cancer patients. There is serious discussion on how to involve patients in designing and evaluating clinical trials, how to assure that patient values and goals are part of the treatment decision making process, how to assure that shared decisions take place throughout treatment. It’s real, and it’s exciting.

ASCO presented Eric Winer, MD with its 2017 Gianni Bonadona Breast Cancer Award. Dr. Winer, a member of the TNBCF Scientific Advisory Board, is the director of the Breast Oncology Center at Dana-Farber and a professor of Medicine at Harvard Medical School. He is a long time leader in both research and patient care, as well as being a remarkable advocate for his patients who takes an active role in many organizations. He has personally led or contributed to dozens of clinical trials that have advanced breast cancer treatment.

“Our understanding of breast cancer biology is better than it has ever been,” Dr. Winer told the ASCO News. “We’re going to continue to see advances over the next couple of years–although many are incremental, the increments are bigger than they were in the past.”

TNBCF congratulates Dr. Winer on this award, one of many he has received in his distinguished career, and thanks him for his wonderful commitment to our work and his contributions to improving the care and treatment of people facing triple negative breast cancer.

Dr. DeMichele is the co-leader of the Breast Cancer Research Program and a medical oncologist at the Abramson Cancer Center of the University of Pennsylvania

For every woman diagnosed with TNBC, the great fear is recurrence. Once primary treatment is completed, there is usually nothing to do but wait for two to five years to learn whether the disease will return and spread. Angie DeMichele, MD., is leading an innovative new program aimed at identifying which individuals are more likely to have a recurrence. It is a key component of her Breast Cancer Center of Excellence program at Penn.

“We are looking for cancer cells that have disseminated but cannot be detected with conventional means,” she says. “These patients have no evidence of disease or have clinically complete responses. But we now know that some cells are resistant to treatment. They escape and ‘hide’ in the bone marrow–and then they just fall asleep and remain dormant until something triggers their growth. These are cells that are most likely to cause recurrence.”

Dr. DeMichele and her group have been doing bone marrow aspirations on patients with all types of breast cancer looking for these dormant cells–and have found them in 30% of patients with TNBC. By itself, that information is important, but the next step is even more critical–intervening to prevent that recurrence.

The CLEVER trial is the first of three planned studies designed to do exactly that. Dr. DeMichele is actively recruiting patients with Stage IIB breast cancer interested in undergoing the bone marrow aspiration to determine if they have dormant cells following their primary treatment. That treatment can include neoadjuvant or adjuvant therapy, surgery and radiation. If the test is positive, patients will receive therapies, HCQ and everolimus, specifically designed to kill those cells and undergo follow bone marrow aspirations.

To be eligible, you need to have been treated within the last six years. You do not need to have received your treatment at Penn.

The plan is to follow CLEVER with two additional trials. The first, CLEAR will test targeted therapy that inhibits the c-met pathway, thought to trigger activity in the dormant cells. C-met is not activated in primary breast cancers, so these therapies are not useful in treating known tumors. GLACIER will be a phase III trial conducted at multiple centers that applies what is learned in the first two studies to a larger population.

GLACIER? That sounds slow, I say, but Dr. DiMichele shakes her head. “I think it suggests something very big and we’re just seeing the tip right now,” she says. “If this works out the way we think and hope it will, it could potentially transform the way we think about response to treatment, and treat women who are at high risk of breast cancer.

To learn more about enrolling in the CLEVER trial, contact Angie DeMichele, MD, at 855-216-0098 or email PennCancerTrials@emergingmed.com.

The headlines read something like, “Pembrolizumab Shows Promise in Metastatic Triple Negative Breast Cancer,” but a closer reading, at least at first, seemed to indicate otherwise. The topic was the much anticipated KEYNOTE-086 Study which tested the efficacy of single agent pembrolizumab (Keytruda) in 170 women with mTNBC, the majority of whom had been treated with at least one chemotherapy regimen. The study included patients with both high and low levels of PD-L1, thought to be a marker for the activity of checkpoint inhibitors.

The overall response rate was 4.7%. Approximately 21% of the patients had stable disease. PD-L1 status had no effect on the response rate. A small percentage of the patients who responded had long lasting responses, including several who were still on treatment 11 months after beginning treatment.

For many, these numbers are disappointing and would not justify using pembro as therapy for this population, which so needs new approaches. But, the story does not end there. There are intriguing data from both this and another trial, the I-SPY 2 study, that suggest there is an important role for checkpoint inhibitors, including pembro, in mTNBC.

The group that did best in the KEYNOTE-086 study were those who had not had any previous treatment for their metastatic disease.

“It’s very possible,” says Angie DeMichele, MD, “that by the time patients have had multiple courses of treatment, their immune systems are worn out. They just cannot mount a response to the tumor. That means, we need to use immunotherapy earlier in the disease process, either as first line treatment for metastatic disease, or in the adjuvant and neoadjuvant setting.”

The I-SPY 2 trial offers strong evidence for that theory. That study is an innovative trial design that allows investigators to adjust patient treatment based on the results as they occur. In that trial, women with high risk TNBC were randomized to either paclitaxel alone or in combination with pembrolizumab. The pac/pembro group had a 60% PCR (pathological complete response), triple that for the paclitaxel alone group.

“We need to have more sensitive markers to help us determine who is going to respond to checkpoint inhibitors, when to to use them and how to combine them with other therapies,” says DeMichele. “We know that TNBC is immunogenic and that these therapies are promising.”

PARP is an enzyme used by normal cells to help repair damage to DNA. Cancer cells, however, use PARP to help them extend their growth. Over the last 10 years, there has been growing evidence that agents that inhibit PARP and prevent cancer cells from repairing their DNA may be useful in treating breast cancers in patients with BRCA 1 and 2 mutations.

The phase III OlympiAD trial provides the first large scale clinical trial evidence to support the use of PARP inhibitors for this population. The study showed statistically significant improvements in progression free survival for metastatic breast cancer patients who received the oral drug Olaparib compared to the physician’s choice of standard chemotherapy. All the patients in the trial had metastatic HER2 negative tumors with germline BRCA 1 or 2 mutations and had received up to two previous lines of treatment.

The trial showed that the tumors shrank in 60% of patients receiving Olaparib compared to 29% of those on chemotherapy. The time to progression was longer, seven months compared to 4.2 months for chemo.

“Olaparib is probably best used early in the course of metastatic breast cancer,” said Mark Robson, MD, Memorial Sloan-Kettering Cancer Center. “It helps preserve quality of life, offers the chance to postpone the need for IV chemotherapy and avoids side effects like hair loss and low white blood cell counts.”

Christine Wilson for TNBC Foundation