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 pembrolizum