Transcript
Announcer:
Welcome to Project Oncology on ReachMD. Today, Dr. Lajos Pusztai will be discussing primary tumor surgery in de novo metastatic breast cancer and the conflicting trial data behind it. Dr. Pusztai is a Professor of Medicine at Yale University and Co-Leader of the Yale Cancer Center Genomics, Genetics, and Epigenetics Program. He’s also Chair of the Breast Cancer Research Committee of the Southwest Oncology Group. Let’s hear from him now.
Dr. Pusztai:
Almost all of the de novo stage four patients that present with oligometastatic or non-oligometastatic disease also have a detectable primary tumor either in the breast or in the lymph nodes. So an important question is, do we also remove the primary tumor, and what is the benefit from it?
So what's really emerging from the clinical trials—NRG-BR002 and the ECOG-ACRIN, which looked at the value of removing the primary tumor only and then subsequently receiving standard care—is that removing the primary tumor without trying to ablate all the other metastatic sites and using a highly effective systemic therapy approach is not helpful.
So the ECOG-ACRIN study is the largest trial. I think the full name is ECOG-ACRIN 2108. And this took de novo stage four metastatic patients. There was no requirement to be oligometastatic. They could also be ER positive, ER negative, and HER2 positive. The vast majority of the patients—about 70 percent of them—were ER positive. And they received some initial endocrine therapy, and then subsequently underwent resection of the primary tumor in the breast. And there was no improvement in overall survival or recurrence-free survival, but of course, there were fewer progressions locally in the breast, chest wall, or lymph nodes.
So that study clearly defines that there's no point in removing the breast cancer alone and leaving all the other lesions in place. But it does not address the question of whether this all-out multimodality therapy, removing the primary tumor, ablating the residual metastatic lesions, and using an adjuvant-like complex regimen could improve the outcome of the patients or not.
There are a number of clinical trials now that try to address this question with a large enough sample size to be conclusive. And probably the largest one is the SWOG trial for HER2 positive patients.
So talking about evidence, there are a couple of other studies which also show similar results like ECOG-ACRIN, and particularly the ABCSG POSYTIVE study. It did not accrue very well, so it had to close early. It was an Austrian and European study that randomized patients in de novo stage four disease to locoregional therapy, mastectomy, lumpectomy, or no surgery—just systemic therapy. And it didn't show any improvement in outcome.
And the third trial, called Tata Memorial, which was an Indian trial, also had a negative result.
So, for full disclosure, there are two other studies which suggest that there is benefit. There is a Turkish randomized trial called MF07, and a Japanese study called JCOG, or J-C-O-G, 1017. So when you have contradictory randomized clinical trials, then this really suggests that, probably, the question is not settled, and positive or negative results are unstable because there is a hidden variable.
And I think that's exactly what I try to convey—that there is a massive hidden variable, and that's how the rest of the disease is treated.
Announcer:
You just heard Dr. Lajos Pusztai exploring whether removing the primary tumor benefits patients with de novo metastatic breast cancer. To access this and other episodes in our series, visit Project Oncology on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!
