William Jacout, MD, a medical oncologist and researcher at the Institut du Cancer de Montpellier Val d’Aurelle in France, detailed the results of a recent paper on the role SPARC proteins may play in patient outcomes, as well as considerations for providers contemplating using genomics to diagnose and direct treatment decisions for patients with breast cancer.
Transcription
He recently published an article on the clinical relevance of SPARC in triple negative breast cancer (TNBC). What can SPARC expression tell us about cancer-associated fibroblasts and TNBC patient outcomes?
Yes, it is the other side of the coin. We’ve focused this past decade on cancer cells, but more and more room has been given to microenvironments. And we look at, in this specific post, fibroblasts and CAFs, fibroblasts associated with cancer. And we saw that, depending on the level of expression of SPARC, this extracellular matrix protein that remodels the extracellular matrix, the high levels of SPARC secreted by CAFs were associated with a more plastic phenotype of tumor cells than cancer cells. triple negative breast and increases its aggressiveness and lowers the prognosis of the population.
So, it’s a big part of one of the teams that I’m working with on preclinical studies. We are currently developing a dedicated anti-SPARC monoclonal antibody to try to create combinations of chemotherapy with this type of targeted therapy.
What are some important factors that providers should consider when using genomics to inform treatment decisions for patients with metastatic breast cancer?
Our first communication had been made last year. First of all, we must focus on what AMALEE is. AMALEE was an FDA-requested Phase 2 randomized study following the approval of ribociclib and the concurrent development of a natural adjuvant trial to look at the side effect mitigation effect of a reduced dose of ribociclib. the [control arm] the dose being 600 mg and in AMALEE, this was compared to a 400 mg dose which is a classic first step of dose reduction.
One thing to note is that the primary endpoint was the overall response rate. And my point of view is probably the stumbling block of this study, because we have to remember that we’re dealing with HER2-positive hormone receptors. [human epidermal growth factor 2]–Negative metastatic breast cancers.
We thought that this was a fairly clear proportion of patients without measurable disease and with bone lesions that are not easy to assess to say that the overall answer was yes or no. So it’s a primary endpoint for us: non-inferiority of the 400 mg dose compared to the 600 mg dose. And last year our first communication was made detailing that this non-inferiority was not met.
Here, we have some more mature data that allows to see the overall response and to see the first assessment of progression-free survival. [PFS], which is probably a more logical end point than that. The overall response rate remained lower, 47% vs. 55%.
However, I must emphasize that the PFS data are exactly identical between the 2 arms at 25 months. So quite reassuring and at the same time with the secondary endpoint of this QD [one dose per day] that was the mitigating effect of reducing the dose with respect to the classic side effects of ribociclib. The first one is a QTc [QT corrected for heart rate] increases and the increase in QTc is significantly less at the 400 mg dose level and, secondarily, the rate of neutropenia.
So that’s something that can’t be said to be inferior in terms of overall response rate. However, with the same PFS and better toxicity profile, it is quite reassuring for clinical practice to say that in case of toxicity, it does not appear that we are missing an opportunity to reduce the dose and alleviate some of the toxic effects.
.
