Trials Show Improved Outcome in Metastatic Breast Cancer Patients

Dec. 7, 201—, 2011 -- For seven years, Suzanne Hebert has undergone treatments, surgeries and chemotherapies to fight off her stage 4 breast cancer. She was diagnosed with the advanced stage cancer at age 39.

By the time doctors found a four-centimeter lump, the cancer had already spread to her spine.

After years of chemotherapy treatments, a mastectomy and hormonal therapy -- during which not only was she "miserable, [but] the treatment wasn't working" -- Hebert joined a phase1 clinical trial out of MD Anderson in Texas, where researchers put her on a combined treatment of everolimus, a drug used to treat kidney and brain tumors, and arimidex, an anti-hormone therapy that decreases the amount of estrogen in the body.

After three months on the novel therapy, Hebert's liver tumor shrunk by 21 percent, and the other cancers did not progress further.

"After all I had been through, it was just unbelievable to see those results," said Hebert. "And the side effects were nothing compared to those for chemo. It was just amazing news."

The therapy is similar to two drugs presented Wednesday at the San Antonio Breast Cancer Symposium. Both trials improved "progression-free survival," a term experts use to measure the length of time during and after medication that the cancer does not get worse.

One kind of cancer responds and grows from estrogen in the body. These tumors are known as "hormone-responsive." Other types of breast cancer are not affected by estrogen. A common treatment for hormone-responsive tumors is anti-hormone therapy, which is meant to prevent breast cancer cells from receiving stimulation from estrogen.

In the BOLERO-2 trial (Breast Cancer Trials of Oral Everolimus), lead study author Dr. Gabriel Hortobagyi, professor and chairman of MD Anderson's Department of Breast Medical Oncology, said the findings demonstrated for the first time that the combination therapies are more effective than a single hormonal treatment in patients who have already tried hormonal therapy.

"Over the years, our treatment approach for such women with metastatic breast cancer has been sequential use of as many hormone therapies as possible, keeping metastatic disease under control for as long as possible," Hortobagyi said. "These findings may allow us to change our approach. In this group of heavily pre-treated patients, all of whom progressed on prior endocrine therapy, the addition of this mTOR inhibitor resulted in significant prolongation of progression-free survival and an improved response rate, with only a modest addition of toxicity."

Researchers enrolled 724 metastatic breast cancer patients into the international phase 3 trial. Study participants were post-menopausal and most had been treated with extensive hormone therapy treatments. Patients were randomized, then 485 received a combination of everolimus (a medication that stops cancer cells from reproducing by decreasing blood supply to the cancer cells) and exemestane (a medication that decreases estrogen in the body). Those patients were then compared to the 239 participants who received exemestane and a placebo.

Participants who received the combination therapy experienced 7.4 months of progression-free survival, compared to the 3.2 months that patients experienced on the placebo.

The trial was partially funded by pharmaceutical giant, Novartis. Hortobagyi acts as a consultant and receives research fund from the company, as well.

"The BOLERO study will likely have the most immediacy in terms of patient care," Dr. Ben Ho Park, associate professor in the oncology breast cancer research program at Johns Hopkins Medical Center, wrote in an email. "The drugs used are already FDA approved and so adding the mTOR inhibitor (everolimus) to aromatase inhibitors would be relatively easy to get widespread usage and may afford oncologists the ability to overcome hormone resistance in a subset of breast cancers."

In a similar, second study presented at the symposium, researchers of the CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) trial found that adding pertuzumab (a medication that is believed to slow tumor growth) and certain chemotherapies lengthened progression-free survival by an average 6.1 months in patients with metastatic breast cancer patients.

"This is huge," Dr. Jose Baselga, lead author of the study and professor of medicine at Harvard Medical School," said in a statement. "It is very uncommon to have a clinical trial show this level of improvement in PFS. ... The fact that we now have an agent that can be added to current treatment to delay progression is very exciting."

While Dr. Vered Stearns, co-director of the Breast Cancer Program at Johns Hopkins, said the results of both trials could be game changers for treatment of metastatic breast cancer patients, progression free survival is a complicated point of treatment.

"The breast cancer community, government agencies and stakeholders should be evaluating what endpoints are most relevant and set proper guidelines," said Stearns.

While some experts argue that progression-free survival lowers the bar for treatment interventions and potential cures, Park said the debate is not so simple.

"It's hard to tell patients that living without overt signs of cancer is of no benefit," said Park. "Symptoms can improve, as well as overall mental well-being. Given the costs and potential side effects associated with new drugs, we understand the reasons behind using certain criteria (i.e. overall survival) as our gold standard for clinical interventions, but this has to be weighed against "meaningful" benefit for patient care which is often harder to define."

Nevertheless, Dr. Jennifer Litton, the principle investigator for Hebert's clinical trial at MD Anderson, said It's always an exciting day to show a patient their tumor has not grown.

"[It's] even better if we can show them their tumor is shrinking, and that they're having a good quality of life -- spending time with their family and doing the things they want to do on their day to day," said Litton.

As for Hebert, the mother of two says the potential for new treatments is a "huge gift."

"I'd like to stay on this treatment as long as possible," said Hebert. "There are so many women out there just like me. We just want options that work better and are less toxic."