Transcript Related Guidelines

In Patients With Metastatic TNBC and a Deleterious BRCA Mutation, How Do You Decide Between a PARPi and an Immunotherapy-Based Combination as Initial Therapy?

Susan Domchek, MD · Basser Center for BRCA


December 09, 2020

Editor’s Note: Based on the recent findings of the phase 3 IMpassion131 study, the US Food and Drug Administration has alerted health care professionals about the lack of efficacy for treating patients with previously untreated, inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC) with the combination atezolizumab + paclitaxel. The IMpassion131 study highlighted the failure of atezolizumab + paclitaxel to significantly reduce cancer progression and death when compared with paclitaxel plus placebo. As atezolizumab + paclitaxel has previously been granted accelerated approval from the FDA for treatment of patients with unresectable, locally advanced, or metastatic TNBC whose tumors express programmed death-ligand 1, the continued approval process may be contingent on future trials that might show benefit from this combination therapy.[1]

This transcript has been edited for clarity.

One of the great things about the research over the past 2 years is that in individuals who have triple-negative breast cancer, there are now two approaches that are novel. One is, in women who have BRCA-1 and 2 mutations, the option of a poly (ADP-ribose) polymerase (PARP) inhibitor, either olaparib or talazoparib.[2,3] In individuals with triple-negative breast cancer, whose tumors have immune cells expressing programmed death-ligand 1 (PD-L1), there is another option, which is the combination of an immune therapy, atezolizumab (Tecentriq), in combination with nab-paclitaxel (Abraxane).[4] So if you have a BRCA-1 or 2 carrier with triple-negative breast cancer, who also has staining for PD-L1, you have one of those two options.

We don't really know which is the best [approach] right now, but there are ongoing studies combining immune therapy with PARP inhibitors. So that's a really good option for the moment, both of these [approaches are a good option], and they seem to work better in the first line. I think this is research that really needs to be done right now to fully characterize this and, off a clinical trial, I think you need to discuss with patients their preferred option as 1/ the PARP inhibitor is an oral therapy, and [2/] the other involves immune therapy but obviously is IV and also has chemotherapy as a part of it.


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