Case 3: POETIC and ADAPT Trials in HR+ High-Risk Breast Cancer
Joyce O’Shaughnessy, MD, reviews the case of a 42-year-old woman with node-positive, HR-positive high-risk breast cancer and discusses clinical data from the POETIC and ADAPT clinical trials.
Joyce O’ Shaughnessy, MD: I wanted to mention 1 other scenario because it may be 1 additional piece of information that we’re leaving on the table. There are new data from Germany. We’re struggling with this woman here, and they say there’s 1 more piece of information you can get. Let’s talk a little about the ADAPT trial. This is the exact same patient, with 1 node positive, strongly ER [estrogen receptor] and PR [progesterone receptor] positive, and Ki67 of 10%, but there are focal areas up to 20%. There’s 1 node positive, a T2 lesion. Those are her clear margins of resection.
Before she goes to surgery, if we get a chance to see her first—or maybe our surgeons can collaborate with this—if she’s got a Ki67 above 10%, should she have 2 or 3 weeks of endocrine therapy preoperatively, or potentially even longer? Who’s a good candidate for longer? If Ki67 suppresses, can it help us avoid chemotherapy? Or if we want to go longer, should we recheck Ki67 and make sure she’s suppressed before we keep going on endocrine therapy?
People, particularly in the UK [United Kingdom], have pioneered the POETIC trial. You get the diagnostic biopsy upfront, you get the Ki67, they get 2 weeks of endocrine therapy, and then they go to surgery. What they’ve shown in this POETIC trial is that the curves we’re looking at—time to recurrence—is 2 weeks of endocrine therapy and looking at baseline Ki67 and then Ki67 at surgery. If they’re low-low—they start low and stay low—they do great with endocrine therapy alone. If they’re high-high—they start high and they don’t suppress—they do very poorly. If they start high and are more than 10% suppressed to less than 10%, they do intermediate. It’s a signal of endocrine therapy sensitivity and how well people will do with endocrine therapy vs needing chemotherapy.
The ADAPT trial from the West German Study Group is innovative. If we look at the red box on the bottom right, we’re looking at a mixture of pre- and postmenopausal women with 0 to mainly 3 nodes positive N1, but they did have an N2 and N3 cohort. But here we’re looking at N0 and N1. Those with 0 to 3 nodes who had a recurrence score of 12 to 25—that’s an intermediate recurrence score. And they got 3 weeks of preoperative endocrine therapy. The premenopausal patients got tamoxifen. The postmenopausal patients got aromatase inhibitor. Then they went to surgery. If they suppressed their Ki67 to 10% or less—that was called suppression—they just got endocrine therapy.
The primary end point was to take these patients who were pN0-N1 but had a really low 21-gene recurrence score, 0 to 11—which is really good—who just got endocrine therapy, and compared those with the patients with N0 to N1 and a higher recurrence score of 12 to 25 who suppressed their Ki67 and just got endocrine therapy to see if they did equally well. The answer was yes. Even though those women had a higher recurrence score—some had node-positive disease—if they suppressed the Ki67 without chemotherapy, they had about a 92.6% 5-year IDFS [invasive disease-free survival]. Those are very good results.
Here we’re looking at distant disease-free survival. Look at the top red box. Those are the premenopausal patients. In both groups, it was a 97% chance of being disease-free at 5 years. This is with the low Ki67 with the suppression. They said that this makes a big difference. This can tell us we can avoid chemotherapy. At the bottom, we see that if patients had 3 nodes positive, they didn’t do as well in this 12 to 25 risk group. They did really well if they were 1 node positive. But with 2 nodes, they did OK. With 3 nodes, we’re not going to be comfortable leaving off the chemotherapy. In Germany, they do this routinely and say this really helps. We see the premenopausal population on the left. We see the endocrine therapy responders, the patients who suppressed their Ki67, the 12 to 25 recurrence score group. Without chemotherapy, look how well they did. And the red is the patients who got the chemotherapy because they didn’t suppress. They did really well.
Transcript Edited for Clarity
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