PARIS – With an expanding array of treatment choices and no fixed algorithm to decide which to use and when, treatment choice for metastatic breast cancer remains based on a conglomeration of tumor biology, prior therapies, toxicities, patients’ performance status and their choice or preference for treatment, Dr. Sandra M. Swain said during a state-of-the-art lecture on metastatic breast cancer at an international congress on anti-cancer treatment.
Compared to 30 years ago when there were only a few drugs available” to treat metastatic disease, “it’s really gratifying to be able to say to a patient, and really mean it, that ‘this is not your last option: we have a lot of other opportunities after this if this treatment doesn’t work or if you don’t like the toxicities from it’,” said Dr. Swain, director of the Washington Cancer Institute at MedStar Washington Hospital Center and professor of medicine at Georgetown University, Washington.
Dr. Sandra M. Swain
The past decade has seen several drugs approved by the Food and Drug Administration for use in metastatic breast cancer: eribulin in 2010, pertuzumab and everolimus in 2012, trastuzumab-DM1 in 2013, and most recently palbociclib in 2015, she said.
Although treatment goals largely remain the same – to extend survival and minimize toxicity, as well as maximizing patients’ quality of life – there has been a shift to looking at the value of metastatic cancer treatment, taking all these factors and the cost of treatment into consideration.
Looking at available chemotherapies listed in the National Comprehensive Cancer Network guidelines, Dr. Swain noted that no one regimen was preferred over others and highlighted the multiple choices that were recommended.
“My preference is to use sequential single agents, unless we have a patient who is very sick and we need an immediate response, “Dr. Swain said. Response rates are often higher with combination regimens but quality of life may be worse or there are added toxicities that need to be factored into the equation.
Dr. Swain highlighted that newer is not necessarily better. Results of the federal-sponsored CALGB 40502 study, for example, showed that neither weekly nab-paclitaxel (Abraxane) or ixabepilone (Ixempra) was better than weekly treatment with paclitaxel (J. Clin. Oncol. 2012;30:Abstr. CRA1002).
“I think in the U.S. this was very important because paclitaxel is generic and much easier for many patients to afford,” Dr. Swain said.
Expanding Treatment Choices
Studies in metastatic breast cancer highlighted by Dr. Swain include the Triple Negative Trial (TNT), the Breast Cancer Trial of Oral Everolimus 2 (BOLERO-2), and the Tamoxifen Plus Everolimus (TAMRAD) study.
Results of TNT were presented at the 2014 San Antonio Breast Cancer Symposium and showed that carboplatin might be a better choice than docetaxel for women with triple-negative breast cancer and the BRCA1/2 mutation.
BOLERO-2 showed that combining everolimus with exemestane increased progression-free survival by 64% in women with ER-positive, HER2-negative postmenopausal metastatic breast cancer who were refractory to treatment with other AIs (N. Engl. J. Med. 2012;366:520-9). The clinical implications of these data were that the use of everolimus could overcome resistance to endocrine therapy although stomatitis can occur within the first 3 months of treatment. Studies are looking at preventing this side effect with a steroid mouthwash, Dr. Swain said.
TAMRAD was a phase II study looking at the combination of everolimus and tamoxifen, showing improved response rates and overall survival over tamoxifen alone in postmenopausal women with AI-resistant metastatic breast cancer (J. Clin. Oncol. 2012;30:2718-24).
Dr. Swain also discussed the recent fast-tracked FDA approval of palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for use in combination with letrozole (Femara) for estrogen receptor–positive, HER2-negative, postmenopausal, metastatic breast cancer.
Approval was based on the results of the PALOMA-1 study (Lancet Oncol. 2015;16:25-35), which showed “a striking benefit, with a 50% reduction in progression-free survival” with the combination versus letrozole alone, she said.
“The biggest side effect is neutropenia,” Dr. Swain cautioned, with around 50% of patients treated with the combination experiencing grade 3 or 4 neutropenia.
“So that’s what we need to be careful of now that this drug is going to be on the market,” she said. While there were no reports of febrile neutropenia in the trial, she felt that this would be seen in the “real world” and needs to be considered.
Whether using granulocyte colony–stimulating factor to prevent neutropenia would be possible or even safe is a topic for future research.
Several phase III studies with palbociclib have been completed or are ongoing. These include PALOMA-2 in combination with letrozole as first-line treatment for ER-positive, HER2-negative metastatic breast cancer; PALOMA-3 in combination with fulvestrant (Faslodex) in patients who have progressed on hormonal therapy; PENELOPE-B in the postneoadjuvant setting; and PEARL in women with ER-positive metastatic breast cancer that is not responsive to treatment with an aromatase inhibitor.