ASCO22: Novel Therapies in Breast Cancer

Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, highlights key advances from the EMBER study and promising data on QOL for HR+/HER2- patients taking checkpoint inhibitors featured at the 2022 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Hello and welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Allison Zibelli, a breast medical oncologist and assistant professor of medicine at the Sidney Kimmel Cancer Center Jefferson Health.  Dr. Zibelli will highlight key posters on breast cancer that will be featured at the 2022 ASCO Annual Meeting. Dr. Zibelli’s full disclosures are available in our show notes, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.  Dr. Zibelli, it's great to have you on the podcast today.  Dr. Allison Zibelli: Thank you. It's nice to be here.  ASCO Daily News: Let's begin with Abstract 1021 and the “Phase 1 EMBER Study.” Can you tell us why this study should be on our radar?  Dr. Allison Zibelli: This study was very interesting because it's testing a novel therapy, which is imlunestrant, an orally bioavailable SERD, or a selective estrogen receptor degrader. This drug is for patients with ER-positive, HER2-negative advanced breast cancer. And they're presenting updated data from the dose-escalation phase and the dose-expansion phase of the EMBER trial.  This trial enrolled 138 patients at a median age of 62 years. The median number of prior therapies for these women was 2. The adverse events were low. They could have prior platinum therapy but no prior fulvestrant or aromatase inhibitor. The premenopausal women in the study received concomitant GnRH antagonist. They had substantial clinical benefit with this therapy with no dose-limiting toxicities.  It had a favorable side effect profile with no cardiac or ophthalmic safety signals, and it had excellent efficacy in patients with heavily pretreated ER-positive advanced breast cancer. This is the first study showing efficacy and safety with an oral SERD. And we're all looking for new oral, well-tolerated therapies for our patients with metastatic estrogen receptor-positive breast cancer.  These patients were heavily pretreated, and they had a median of 2 prior therapies. Most of the patients with advanced breast cancer had prior endocrine therapy, 92% had a prior CDK 4/6 inhibitor, 50% had fulvestrant, and 26% had chemotherapy.  Despite this, they had an overall response rate of 5% with a clinical benefit rate of 47%. So, it'll be very interesting for us to see what happens with this new class of SERDs in the future.  ASCO Daily News: Excellent! So, moving on to Abstract 514. This study addressed patients with high-risk early breast cancer who received pembrolizumab within the new adjuvant biomarker rich I-SPY 2 trial. Can you tell us more about this study?  Dr. Allison Zibelli: This is a very interesting study, which is a platform study comparing various investigational treatments to a standard therapy which was ACT, with or without herceptin, depending on the HER2 status of the patient versus an experimental agent.  One arm of the I-SPY study was neoadjuvant pembrolizumab. This paper is very interesting to me because it's hard to know in advance who will respond to immune checkpoint inhibitors. And that's what this study was designed to answer.  So, they took 69 patients who were on the I-SPY study, they all had high-risk MammaPrint scores, and all of them were HER2 negative, and with these patients, they had 31 complete responses to neoadjuvant pembrolizumab and 38 patients with a residual disease after neoadjuvant pembrolizumab. Notably, of the 31 complete responses, 12 were ER-positive, and 19 were triple-negative.  In the residual disease patients, 28 were ER-positive and 10 were triple-negative. If you compare this with historical data, the response rate for pembrolizumab is about 20% for patients who are triple-negative and about 12% for patients who are ER-positive.  So, the response rates that they had were higher in general. So, what the study did was they found a signature of 53 genes which they named imprint, which was identified with a greater than 90% sensitivity and greater than 80% specificity for predicting complete response to pembrolizumab in all patients.  This worked equally well for the patients who are estrogen receptor-negative and estrogen receptor-positive. In KEYNOTE-086 cohort B, which was presented at the American Association for Cancer Research Annual Meeting (AACR), PD-L1 of greater than 1% only predicted a 23% response rate to pembrolizumab.  So, if we could use the imprint study to predict patients who would respond to pembrolizumab, it would save a lot of needless toxicity and a lot of needless expense, in treating the patients who would have benefit.  So, this is going to be a very useful method to identify patients that we want to treat with pembrolizumab, and perhaps other immune checkpoint inhibitors as well. I think this might be the next “Oncotype” as it were, in that it will be able to predict who will benefit from a specific therapy.  ASCO Daily News: Thank you! Let's move on to Abstract 519. This is a randomized pre-surgical trial of alternative dosing of exemestane in postmenopausal women with early ER-positive breast cancer. What are your key takeaways here?  Dr. Allison Zibelli: I thought this was a great design of a study. It was a window of opportunity for the test. So, what they did was, they tested 3 different dosing schedules of exemestane in patients waiting for surgery for ER-receptor-positive breast cancer.  The patients were randomly assigned to either receive exemestane 20 milligrams a day, the standard schedule, 25 milligrams 3 times a week, or 25 milligrams once a week for 4 to 6 weeks prior to surgery.  Their endpoint was percent decrease in circulating estradiol and what they found was the 3 times a week schedule was comparable to the daily schedule. The once-a-week schedule didn't seem to be adequate to decrease estradiol, but 3 times a week was equivalent to daily.  This was really interesting because we know that our patients have difficulty tolerating aromatase inhibitors. We know from formal studies that about 25% of patients discontinue aromatase inhibitors prematurely because of side effects. Small studies in actual practice settings show it's probably even higher than that—between 30 and 50% of patients discontinue aromatase inhibitors.  So, for the patient that can't tolerate daily therapy, 3 times a week therapy is an attractive option, that may be just as good as daily. I think it is very important for patients who have to take these drugs for years that they have a way to take them that is tolerable.  ASCO Daily News: Absolutely. Well, the last study I'd like to ask you about is Abstract 1015. This looks at the quality of life for patients with HR-positive, HER2 negative advanced breast cancer. So, what does this study tell us about quality of life with different CDK 4/6 inhibitors?  Dr. Allison Zibelli: So, we have a lot of studies of CDK 4/6 inhibitors. And we know that they dramatically improve the overall survival of women with ER-positive metastatic breast cancer. What we also know is that they have a lot of side effects. And for women that have to take these drugs for years, that's important.  So, this study was a matching adjusted indirect comparison study. This is a method that uses individual patient data to create balanced trial populations across separate studies, and they use patients from the MONALEESA-2 trial, which was ribociclib plus AI, compared to MONARCH 3, which used abemaciclib plus AI, the endpoint was something they called “time to sustain deterioration,” which was a decrease in 10 points in the quality of life score, they use the QLQ-C30 questionnaire. The upshot of their data was that ribociclib was more tolerable, mostly with less appetite loss, less diarrhea, and less fatigue than abemaciclib.  So, this is 1 of the first studies we've seen that directly compares, well sort of directly compares the quality of life between these 2 drugs, and this may be a data point that favors ribociclib.  ASCO Daily News: Well, thank you, Dr. Zibelli, for highlighting some really important advances in breast cancer that will be featured at the 2022 ASCO Annual Meeting. We really appreciate it.  Dr. Allison Zibelli: Thank you very much for having me.  ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the ASCO Daily News podcast. Please take a moment to rate review and subscribe wherever you get your podcasts.  Disclosures:   Dr. Allison Zibelli: None disclosed.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.