Eric Winer, MD, Director, Yale Cancer Center and Professor of Medical Oncology, Yale School of Medicine
My name is Eric Winer. I'm a medical oncologist. I have spent most of my life focusing on breast cancer and breast cancer research. I, for many years, was at the Dana-Farber Cancer Institute where I ran the breast cancer program. And I'm now the Director of the Yale Cancer Center and the President of Smilow Cancer Hospital.
So, this year's ASCO meeting was great. As always, it was held in Chicago. We had approximately 44,000 attendees, which was nearly a record.
There were a whole range of new advances that were presented, many in my field of breast cancer.
The drug trastuzumab deruxtecan (T-DXd), otherwise called ENHERTU, was looked at in a first line metastatic setting. It compared the drug ENHERTU with standard chemotherapy and antibodies.
And among the patients who receive standard chemotherapy, the chemotherapy was stopped after a matter of months and antibodies were continued.
And what the study demonstrated was that women who received ENHERTU or trastuzumab deruxtecan had a much, much longer time of disease control. And in fact, about three and a half years was the time that patients were on this treatment. Or in some cases they would stop the treatment because of side effects and just be followed.
But that's a long time and I think is emblematic of the dramatic advances we've made in the treatment of HER2-Positive breast cancer in general and HER2-Positive metastatic breast cancer.
I'll also add that there was a study presented that was published in the New England Journal of Medicine that I think is very important, that is a study that randomized patients with colon cancer to receive either an exercise intervention or just exercise education, meaning they got a pamphlet about how to exercise more as opposed to getting training and coaching.
That study showed that the group of individuals who had structured exercise actually had dramatically fewer recurrences and a longer survival, which given the fact that exercise is something that's good for so many different parts of us, the fact that you could put somebody with cancer through an exercise intervention. And it would help them do better is just incredibly exciting to me.
Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04
Sara Tolaney, MD, MPH, Chief of Breast Oncology at Dana-Farber Cancer Institute and Assoc. Professor of Medicine at Harvard Medical School
My name is Sarah Tolaney, and I'm a breast medical oncologist at Dana-Ferber Cancer Institute.
At ASCO this year, we presented results of ASCENT-04, which is a randomized phase three trial looking at sacituzumab govitecan plus pembrolizumab compared to chemotherapy plus pembrolizumab in patients who have PD-L1 positive, metastatic triple-negative breast cancer that are previously untreated in the metastatic setting. So really a first line clinical trial.
We've known for a little while now that sacituzumab govitecan is a highly effective antibody-drug conjugate. It targets Trop-2 and delivers a cytotoxic topoisomerase 1 payload. And it is approved currently as a second line and beyond standard of care, where it's already shown improvements, both in terms of progression-free survival and overall survival in pretreated triple-negative breast cancer.
But we had really robust preclinical data and some clinical data suggesting that the combination of an antibody-drug conjugate and a checkpoint inhibitor could potentially be synergistic. And so, we were quite interested to see how sacituzumab and pembrolizumab would do and compare to chemotherapy and pembrolizumab.
So, patients who had previously untreated metastatic, triple-negative breast cancer that was centrally confirmed to be PD-L1 positive got randomized one-to-one to get sacituzumab plus pembrolizumab or chemotherapy, a physician's choice, plus pembrolizumab where chemotherapy options could include paclitaxel or nab-paclitaxel or carboplatin and gemcitabine.
And for those patients on the chemotherapy plus pembrolizumab arm, they could cross over to receive sacituzumab govitecan and monotherapy, which was actually offered and provided on the trial during the crossover phase of the study for those patients who had centrally confirmed disease progression on the chemotherapy and pembrolizumab.
And so the primary endpoint was to look at progression-free survival by blinded independent central review, comparing sacituzumab govitecan plus pembrolizumab to chemotherapy plus pembrolizumab
And what we saw was that the sacituzumab and pembrolizumab did do much better than the chemotherapy and pembrolizumab, where there was really a statistically significant and clinically meaningful improvement in PFS with a PFS of 11.2 months for sacituzumab and pembrolizumab compared to 7.8 months for the chemotherapy and pembrolizumab with a hazard ratio of 0.65 and an absolute difference between the two arms of 3.4 months.
There was no formal statistical testing for overall survival but there was an early trend with a hazard ratio 0.89.
These data to me are really exciting because it suggests that we are doing better for patients with metastatic, triple-negative disease, which unfortunately is a very aggressive subtype of breast cancer where we know that half of our patients who start first-line therapy for metastatic, triple-negative disease actually can never go on to get a second-line of treatment either due to deterioration in health or death.
And so, getting effective first-line therapies for patients is really important. And to see this improvement with sacituzumab and pembrolizumab is exciting and hopefully will become a new, potential standard of care.
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