William Jacout MD is a French medical oncologist who also works at Institut du Cancer de Montpellier Val d’Aurelle. He presented results from a paper on the role of SPARC proteins and patient outcomes. He also discussed considerations for providers that might use genomics to guide treatment decisions for patients with breast cancer.
You recently published a paper on the clinical significance of SPARC in triple-negative breast cancer (TNBC). What does SPARC expression tell us about TNBC-associated Fibroblasts?
There’s also another side to this coin. Over the past decade, we have primarily focused our attention on cancer cells. However, microenvironments are gaining more attention. This publication included both fibroblasts and CAFs (cancer associated fibroblasts). In triple-negative breast cancer cells, we found that the SPARC (extracellular matrix protein remodeling extracellular matrix), was associated with a more plastic phenotype. This makes them more aggressive and lowers their prognosis.
It is an integral part of the preclinical research team that I am part of. We are currently developing a monoclonal anti SPARC antibody to create combinations of chemotherapy with this type of targeted therapy.
How can providers use genomics to make treatment decisions for patients with metastatic breast cancer?
Last year was our first communication. We must first focus on AMALEE. AMALEE was a phase 2, randomised study. FDA requested it following approval of Ribociclib. FDA approved a trial using ribociclib to assess the side effects mitigation effect at reduced doses. AMALEE compared the 600 mg dose to [control arm] with a 400 mg dosage, which is a classic first-step reduction in dose.
It is important to emphasize that the primary endpoint was the overall response rate. This is likely to be my interpretation of the problem in this study. We’re dealing with hormone receptor-positive, human Epidermal Growth Fact 2,-negative metastatic breast cancers.
This was an interesting group of patients, with no measurable diseases and bone lesions which are hard to evaluate to determine whether the answer is yes or no. Our primary goal is to achieve non-inferiority in the doses of 400 mg and 600 mg. Our first communication last year confirmed that this was not true.
Now we have mature data which allows us to see both the overall response and the first evaluation for progression free survival [PFS], which might be a better logical conclusion. The overall response rate was 47% lower than the 55%.
The progression-free survival data for both arms at 25 months is almost identical. This is encouraging and also serves as a secondary endpoint for the QD [one day dose] which had the mitigating effects on reducing doses concerning the classic Riboclib side effects. A QTc [QT corrected for heart rate] increase. The dose of 400 mg has a significantly lower QTc, and secondly, neutropenic rates.
In terms of overall response rates, this is not an inferiority. It is possible to reassure the clinical practice that even though the PFS is identical and the toxicity profile better, there are still chances to reduce the dose or minimize the toxic effects.