Cisplatin plus/minus veliparib in metastatic TNBC and/or germline BRCA-associated breast cancer

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Published: 29 May 2020
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Dr Julie Gralow - University of Washington School of Medicine, Seattle, USA

Dr Julie Gralow speaks to ecancer online about her ASCO 2020 virtual presentation which discussed the SWOG S1416 trial.

SWOG S1416 was a phase II randomised trial of cisplatin /- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer.

She explains the reason for choosing veliparib for this study, and the general trial design.

Dr Gralow explains the results, good for the BRCA patients, before touching upon the side effects.

SWOG S1416 was a trial that was actually piloted in Seattle at the University of Washington and the Seattle Cancer Care Alliance. Because of promising results we took it to SWOG, a big US NCI cancer research network, and the trial was triple negative breast cancer patients or those with a germline mutation in BRCA1 and 2. Everybody got cisplatin as either first or second line treatment for metastatic disease and then patients were randomised to receive veliparib, a PARP inhibitor, or not.

Now, what’s interesting is we have a couple of PARP inhibitors that are already FDA approved as single agents in breast cancer as well as ovarian and now prostate but you can’t add them to chemo because of toxicities, particularly anaemia and neutropenia. We haven’t been able to add olaparib or talazoparib, for example, to chemo. Veliparib doesn’t have as much toxicity to the bone marrow cells and so even though its single agent activity hasn’t yet been proven as much as the other drugs, its ability to be added to chemotherapy is much higher. So that was the basis for this.

We broke the people who enrolled in the study up into three groups. One was those who had a BRCA1 or 2 germline mutation and that, actually, did not meet its accrual goal. We only had 37 patients and that was because the other PARP inhibitors had been approved during the course of the trial and so they could get the PARP inhibitor off-study. I think that’s the main reason we didn’t accrue. Then for the rest who were triple negative we did a bunch of assays looking at what we call BRCAness. So this was looking for homologous repair deficiency and other features of triple-negative breast cancer that made it act more like it had issues in homologous repair deficiency, more like a BRCA1 or 2 mutant cancer would. So, of those triple negative breast cancer patients it was almost 50-50, those who met the criteria by our experimental assays for homologous repair deficiency or BRCAness and not. What we showed was that in that group, it was about 100 patients who had the HRD or the BRCAness feature and were triple negative, they did benefit from the addition of veliparib to cisplatin. The progression free survival was 5.7 months versus 4.3 months and that met statistical significance. The other half who did not have those BRCA-like features did not seem to have any benefit from veliparib. The group that had the germline BRCA1 and 2 mutations, which I told you was small and we didn’t meet our accrual goal, there was at least numerically a trend towards benefit for the addition.

So I think that this study shows some interesting findings combining PARP inhibitors when they can be combined and neutropenia and anaemia were the biggest side effects that were greater in the combination group, to get better outcomes for our patients. We’re still following up on overall survival, we don’t have any solid data on that yet.