Denise Yardley, MD
The encouraging findings with the alpha-specific PI3K inhibitor alpelisib in patients with PIK3CA
-mutant breast cancer coincide with the refined, personalized approach being implemented in breast cancer treatment, explained Denise A. Yardley, MD.
In the primary analysis of the phase III SOLAR-1 trial, the combination of alpelisib and fulvestrant (Faslodex) was associated with a median progression-free survival (PFS) of 11.0 months in patients with PIK3CA
-mutant advanced breast cancer compared with 5.7 months for those who received placebo plus fulvestrant at a median follow-up of 20 months. This translated to a 35% reduction in the risk of disease progression or death (HR, 0.65; P
Additional analyses of the trial, which were presented at the 2018 San Antonio Breast Cancer Symposium, showed that alpelisib plus fulvestrant extended PFS versus fulvestrant alone in this patient population, regardless of line of therapy or prior CDK4/6 inhibitor treatment.2
Moreover, the median OS has not been reached in the alpelisib arm, according to an interim analysis.
“Opportunities are there. There are lots of drugs, the science is fabulous, and the industry is really continuing to offer drugs for our patients on clinical trials,” said Denise Yardley, MD. “This year, we are going to see some FDA approvals and it’s an exciting time in 2019.”
In an interview during the 2019 OncLive®
State of the Science Summit™ on Breast Cancer, Yardley, senior investigator, Breast Cancer Research Program, Sarah Cannon Research Institute, discussed key data presented at the 2018 SABCS and the impact of the SOLAR-1 findings.
OncLive: What would you define as the most practice-changing studies from the 2018 SABCS?
: SABCS continues to build on a changing standard of practice for patients facing a diagnosis of breast cancer. What we are continuing to see, as a big message, is trying to define our treatment recommendations. For early-stage patients, it is trying to decide on which patients need chemotherapy, who can avoid chemotherapy, and then for those who are going to benefit from endocrine therapy, [who should receive] the extended endocrine therapy. We are seeing not the one-size-fits-all approach anymore; it’s really tailoring it on a case-by-case basis. In my practice, my discussions become longer and longer trying to assimilate the data and bring the patients into that patient-physician partnership to try to make these treatment decisions.
In the metastatic setting, we are also seeing the ability to try and refine our treatments. As we see more and more trials with niche populations in the metastatic breast cancer setting, we are learning that genomic profiling of breast cancer tumors is extremely important—in the metastatic setting, even upfront, even for the hormone receptor (HR)–positive patients. We had updates with the SOLAR-1 data, which were initially presented at the 2018 ESMO Congress, looking at the importance of PIK3CA
mutations. Even though we [had data with] the PI3K/ATM/mTOR pathway with everolimus (Afinitor) in the BOLERO-2 trial, now we have the SOLAR-1 data. [It showed that], yes, there is benefit from these targeted agents and this is a reason to profile—to identify patients with the PIK3CA
We saw exciting data with immunotherapy for the first time—we saw that enter the realm of breast cancer with a strong signal. I have had partners in our practice at Sarah Cannon Research Institute that have a longstanding history in lung cancer with immunotherapy. But now, breast cancer actually rocks with immunotherapy. That is confined to triple-negative breast cancer (TNBC) in the first-line setting. On top of that, it is for PD-L1–positive tumors. Therefore, we are really learning to tailor our treatment recommendations for different subtypes and the precision of different mutations in breast cancer. Making those treatment decisions are really hinging on having those data available.
Are more patients in your practice inquiring about immunotherapy following the IMpassion130 data?
I see patients really struggling with the data. Various patients come in with newspaper clippings, and all have some pertinence to immunotherapy—whether it’s a signal or whether it’s as bench work in the basic science labs. It is more challenging to explain to them why this [class of] drugs, which are approved in many other solid tumors, has been struggling in breast cancer. I take the dialogue that breast cancer is not a one-size-fits-all [approach]. There are multiple subtypes, and the biology of these subtypes are very well etched out; we are seeing how therapies work and don’t work in these specific subtypes.