Transcript

I'm Dr Julie Gralow. I'm the Director of Breast Medical Oncology at the Seattle Cancer Care Alliance, and the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington. I'll be discussing some abstracts that will be presented at the ASCO 2020 virtual scientific meeting.

The SWOG S1416 study is an interesting trial that was actually piloted in Seattle and then moved into the cooperative group setting, because of some interesting pilot results.

This is a trial of patients with either triple-negative breast cancer in the metastatic setting who have received at most one prior line of therapy or patients with metastatic breast cancer with the BRCA1 or BRCA2 germline mutation. All of those patients were allowed to enroll, everybody got cisplatin chemotherapy, and half the group had the addition of veliparib.

Veliparib is a PARP inhibitor, and it is able to be added to chemotherapy. Now, this is different from some of the other PARP inhibitors that we already have approved in breast cancer, olaparib and talazoparib, which really because of their impact on the bone marrow, the red cells and the white cells can't be added at full doses to chemotherapy.

Veliparib has less of an impact on the red cells and the white cells and can be added at a dose that appears to be efficacious to chemotherapy. That was the idea behind this study. Now, we already know that PARP inhibitors work in BRCA1 and 2 germline mutated tumors, and we have two PARP inhibitors approved in that setting. When the study started, we didn't though.

The results were that in that group, we actually couldn't accrue enough patients so that we only had 37 patients partway through the PARP inhibitors were approved. We showed a numerical but not a statistical benefit for adding veliparib in the 37 patients who enrolled with a germline BRCA1 or 2 mutations.

Now, another couple hundred patients had triple-negative breast cancer. In those patients, we did a lot of interesting studies. First of all, we tested them all for germline BRCA1 and 2. We tested them for somatic mutations in BRCA1 and 2, we looked at other DNA repair genes, and we looked at an assay for homologous repair deficiency, or homologous recombination deficiency, or HRD.

That is an assay looking for what we call BRCA eNOS. We know the BRCA1 and 2 are involved in homologous repair, recombination deficiency, and so triple-negative breast cancers that have this HRD positivity or BRCA eNOS might also benefit from PARP inhibitors. That was our hypothesis.

About half of the triple-negative patients had this HRD or BRCA eNOS, and the other half didn't. In the group that did have the HRD, we found that veliparib statistically added in terms of progression-free survival to cisplatin. In the group that was just standard triple-negative without the HRD positivity, veliparib did not add.

It was an interesting study. I'm very excited. This is the first time we've shown a combination of chemo and a PARP inhibitor in a group of non-germline BRCA1 and 2 patients, but a group that has a BRCA eNOS that we can test in assays. This was a randomized phase 2.

We need to further investigate this triple-negative group with a positive HRD, and explore this further, but very exciting for our triple-negative breast cancer patients who up until recently, haven't had a lot of treatment options in the metastatic setting beyond classic chemotherapy. We're excited that this was a positive study, and we look forward to exploring this combination further.