Highlights From ASCO 2012 Breast Cancer Symposium

The American Society of Clini­cal Oncology 2012 Breast Can­cer Symposium, held September 13-15 in San Francisco, California, offered all members of the cancer team an upfront view of new data and an opportunity for one-on-one interaction with experts. The following are a few research items of interest to oncology pharmacists.

Palonosetron Most Effective in Preventing Treatment Delays
Among early-stage breast cancer patients initiating a highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) regimen, palonosetron was associated with a significantly reduced risk for chemo­therapy-induced nausea and vomiting (CINV). It also was associated with a lower rate of delayed therapy with MEC (equal to HEC) and higher adherence to MEC regimens (equal to HEC), compared with other 5-HT3 receptor antagonists in a comparison led by Hope S. Rugo, MD, of the Uni­versity of California San Francisco (Abstract 75).¹ The study was an observational case-control study that employed medical and pharmacy administrative claims data from the HealthCore Integrated Research Database. Patients were treated according to National Compre­hensive Cancer Network guidelines between 2002 and 2010.

Patients received palonosetron, dola­setron, granisetron, or ondansetron at the start of chemotherapy and for 5 days during their index treatment. Outcomes with palonosetron were compared with outcomes pooled together from all other antiemetics.

Follow-up was defined as the duration of time between the index data and the earliest occurrence of any of the following: switching from a single-day HEC/MEC regimen to a multiday index HEC/MEC regimen, augmenting the index regimen with nonindex drugs, death, end of health plan eligibility, and end of available data stream. CINV was defined as having at least 1 acute (on chemo­therapy start date) or delayed (at 5+ days) CINV event.

Patients receiving palonosetron for MEC had a 39% reduced risk of having 1 or more CINV events, compared with those receiving other 5-HT3 agents (P <.0001), and a 49% reduced risk when they received HEC (P <.0001). No statistically significant difference in treatment delays due to CINV was found for palonosetron versus other agents in the HEC cohort. Among the MEC cohort, however, the need to delay therapy was reduced by 63% with palonosetron (P = .0005).

Adherence to treatment also was significantly higher with palonosetron, versus other agents, in the MEC cohort (P = .02) but not in the HEC cohort.

Vascular Toxicities Do Not Lead to Endocrine Therapy Discontinuations
A large retrospective cohort study of 629 postmenopausal women treated with endocrine therapy found a high incidence of vascular toxicities, but a low rate of treatment discontinuations because of this (Abstract 68).² The vascular toxicities were consistent with those described in published reports: with aromatase inhibitors, an increase in cardiovascular events and hypercholestero­le­mia; and with tamoxifen, a higher incidence of thrombosis.

Vascular toxicities were observed in 37% of patients receiving tamoxifen and 25% to 35% of patients on aromatase inhibitors. The most common toxicities seen with tamoxifen were peripheral edema (23.2%) and thromboembolic events (7.1%). Patients on aromatase inhibitors were also likely to have peripheral edema (19%), as well as hypercholesterolemia (5.4%), arrhythmia (5.2%), and cardiovascular events (4.8%). Pre­existing vascular comorbidities significantly increased the risk of developing a new vascular toxicity if the patients were taking letrozole or tamoxifen.

Treatment was discontinued due to vascular toxicity 3 times more often with tamoxifen (11%) than with an aromatase inhibitor (3%), mostly due to thromboembolic events (7.1% vs 2.9%).

“These results are encouraging and suggest that the risk of vascular toxicities should not preclude selection of the optimal endocrine strategy,” said Susan F. Dent, MD, of the Ottawa Hospital Cancer Centre in Canada.

Metformin May Reduce Risk of Developing Breast Cancer
A meta-analysis of published studies found that metformin use in women with diabetes is associated with a 17% lower risk of developing invasive breast cancer (Abstract 25).³ The analysis identified 443 studies, of which 7 (all observational) met study criteria. Dia­betic women taking metformin experienced an overall 17% reduction in the risk of breast cancer. The risk reduction was 25% for those taking the drug for more than 3 years, and 6% when exposure was 3 years or less. Older studies (prior to 1997) also found a greater association.

“Because this finding is based upon observational studies, it may reflect bias or confounding,” acknowledged Rowan T. Chlebowski, MD, PhD, of the David Geffen School of Medicine at the University of California Los Angeles. “But the finding of a stronger effect size associated with studies of longer duration of metformin use and those that had longer observation periods suggest that the finding may be real. If the result is confirmed in prospective studies with a large number of breast cancer events, clinical trials should assess whether metformin can reduce breast cancer risk.”

Statin Use Ameliorates Risk of Bone Metastasis
The use of statins was associated with a reduced risk of bone metastases in breast cancer and improved disease-free survival (Abstract 40).⁴ The study, by investigators from Albert Einstein Medical Center in Philadelphia, Pennsylvania, was a retrospective review of 841 stage I to III breast cancer patients, stratified ac­cording to the use of statins for 3 months or longer. Patients who used statins had a 51% reduction in metastasis to the bone, but not to other sites. Their median disease-free survival was 63.6 months versus 53.9 months among nonusers.

Gentry T. King, MD, explained that the mevalonic acid pathway has been implicated in the promotion of a microenvironment for bony metastasis from breast cancer. The statins, which act on this pathway, have in vitro antineoplastic and antiosteoclast activity against breast cancer through interference with this pathway.

“I would not yet prescribe a statin for the purpose of reducing bone metastasis risk,” he said, “but if patients are already on them, because of the possible protective effect, I would certainly not take the patient off the statin.”

References

1. Rugo HS, Palli S, Grabner M, et al. The impact of 5HT3RA antiemetics on the incidence of chemotherapy-induced nausea and vomiting (CINV), treatment adherence, and delay of therapy in early-stage breast cancer (BC) patients treated with moderately/highly emetogenic chemotherapy (MEC/HEC). Presented at: American Society of Clinical Oncology 2012 Breast Cancer Symposium; September 13-15, 2012; San Francisco, CA. Abstract 75.
2. Dent SF, Crawley FL, Graham NA, et al. Vascular toxicities of endocrine therapy in early-stage breast cancer: encouraging observations in a nontribal setting. Presented at: American Society of Clinical Oncology 2012 Breast Cancer Symposium; September 13-15, 2012; San Francisco, CA. Abstract 68.
3. Col N, Ochs L, Springmann V, et al. Metformin and breast cancer risk: a meta-analysis and critical literature review. Presented at: American Society of Clinical Oncology 2012 Breast Cancer Symposium; September 13-15, 2012; San Francisco, CA. Abstract 25.
4. King GT, Yun JH, Chae YK, et al. Statin use and the development of bone metastasis in breast cancer patients. Presented at: American Society of Clinical Oncology 2012 Breast Cancer Symposium; September 13-15, 2012; San Francisco, CA. Abstract 40.