Debu Tripathy, MD
A number of crucial findings were presented over the course of 2015 that helped to characterize an ever-growing trend toward personalized medicine in the treatment of breast cancer, according to Debu Tripathy, MD, who presented a talk focused on highlights from the 2015 ASCO Annual Meeting and the 2015 San Antonio Breast Cancer Symposium (SABCS).
To fully capture the top research, Tripathy compiled a list of 10 key studies that were presented at the two meetings. These intriguing clinical trials provide new insight into existing therapies while fueling immunotherapy excitement, noted Tripathy chair, Breast Medical Oncology, The University of Texas MD Anderson Cancer Center.
“While there are some challenges with personalized medicine, our knowledge in that area is growing,” said Tripathy. “Becoming a state-of-the-art breast medical oncologist really takes a lot of knowledge and understanding of these trials and that’s what our hope is to do is to present data that are coming out of the research world and translating them into how we actually take care of patients.”
Optimizing DCIS Treatments
A number of intriguing clinical trials focused on the treatment of patients with hormone receptor (HR)-positive breast cancer, including those with ductal carcinoma in situ (DCIS). Chief among these studies were updates from the phase III IBIS-II study and the NSABP B-35 trial, which compared tamoxifen and anastrozole for postmenopausal women with DCIS.
In the IBIS-II study (Cuzick J, et al. SABCS; abstr S6-03), breast cancer recurrences were similar between the two hormonal therapies, although there was a significantly higher rate of secondary cancers in the tamoxifen arm. Overall, there were 17 gynecologic cancers in patients who received tamoxifen versus one in the anastrozole arm. Additionally, thromboembolic events were more common with tamoxifen versus anastrozole (24 vs 7, respectively; P
The rate of nonmelanoma skin cancers was lower in those receiving anastrozole (odds ratio [OR], 0.43; P
= .04). However, more patients in the anastrozole arm experienced fractures compared with tamoxifen (OR, 1.36; P
In the NSABP B-35 trial (Ganz PA, et al. SABCS; abstr S6-04), a significant 27% reduction was seen in recurrence with anastrozole compared with tamoxifen (P
= .03). Moreover, a difference was not observed in overall quality of life between women in the tamoxifen and anastrozole groups for physical or mental component scores using the SF-12 tool (P
= .02 and P
= .38, respectively).
“Treating DCIS with anastrozole versus tamoxifen is something that can be applied in the clinic right now,” said Tripathy. “Anastrozole is a better drug and has a lower rate of contralateral recurrence and has a better side effect profile in some cases.”
Adding Denosumab Improves DFS
A follow-up analysis found that adding denosumab to an aromatase inhibitor (AI) helped to prevent fractures while reducing the risk of recurrence and death in postmenopausal women with HR-positive breast cancer (Gnant M, et al. SABCS; abstr S2-02). The addition of low-dose denosumab to an AI reduced the number of clinical fractures by half, with 176 fractures reported in patients receiving placebo, and only 92 fractures observed in the denosumab arm (HR, 0.50, P
“Denosumab has really been shown to lower the fracture rate, and there is a borderline improvement in recurrence risk,” said Tripathy. “How we use bone-targeted agents in early phase disease–whether it is just for bone density and fracture or whether it actually has an adjuvant effect in lowering the risk of recurrence–is of interest.”
In the longer follow-up, women treated with denosumab plus standard AI therapy experienced a 19% relative improvement in disease-free survival (DFS). The absolute benefit was about 1% after 3 years, 2% after 5 years, and 3% after 7 years of follow up. Additionally, benefits may be greater for those who start treatment earlier (HR, 0.61) and for those with larger tumors (HR, 0.66).