ASCO 2022 Breast Cancer Overview: MOASC Spotlight
DESTINY-Breast04 Data from ASCO 2022 Annual Meeting
I presented a lot of data today because such exciting results came from 2022 ASCO annual meeting to this year. I first presented DESTINY-Breast04 studies, which showed. Significant improvement in progression-free survival and overall survival (OS) for HER2 positive breast cancer, in breast cancer research. Her2-Low metastatic breast cancer in a subset analysis or exploratory analysis in the hormone receptor (HR) negative, HER2-Low metastatic breast cancer patients. We did also see a benefit improvement in PFS and OS, even though it’s a small group of patients. It’s very impressive. So, we’re very excited that we now have this new FDA-approved therapy targeting HER2-Low disease, the first ever.
Key Points From The DESTINY-Breast04 Breast Cancer Clinical Trial
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Is unresectable or metastatic breast cancer
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Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
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Is HER2 positive breast cancer or hormone receptor (HR)-negative breast cancer
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Has progressed on, and would no longer benefit from, endocrine therapy
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Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the metastatic disease setting
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Was never previously HER2 positive breast cancer (ICH 3+ or ISH+) on prior pathology testing (per this year’s American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)
TROPiCS-02 Clinical Trial (Trastuzumab Deruxtecan) For HER2 positive, Her2-Negative Breast Cancer
We are hoping that we can expand on this landscape of novel ADCs (antibody drug conjugates) in order to provide improved cure rates for earlier-stage breast cancer, as well as first an earlier line setting for metastatic breast cancer research (breast cancer care). Then I presented the study with the TROPiCS-02 trial (Trastuzumab Deruxtecan) where it is looking at other ADCs (antibody drug conjugates), that target Trastuzumab Deruxtecan in heavily pretreated, independent refractory hormone receptor positive, Her2-negative breast cancer.
In the metastatic cancer setting and in that study, we also saw an improvement in progression-free survival and improvement in the progression-free survival rate at 6, 9, and 12 months. And interestingly, we also saw an improvement in quality for cancer patients who are treated with Sacituzumab compared to patients that received chemotherapy. With that, we now have another choice for our patients in terms of having another treatment line available for them using Sacituzumab.
2022 ASCO Annual Meeting – Survival Data: PALOMA-2 In Hormone Receptor Positive Estrogen Receptor (ER)+/HER2- Advanced Breast Cancer
Next at 2022 ASCO annual meeting, I presented the PALOMA-2 OS data in estrogen receptor (ER)+/HER2- advanced breast cancer (who were taking aromatase inhibitors) where, unfortunately, we saw no significant benefit from using Palbociclib with Letrozole (upfront endocrine therapy) compared to Letrozole in the first line setting for patients with estrogen receptor (ER)+/HER2- advanced breast cancer(who were taking aromatase inhibitors). It’s unclear to us why there is a lack of OS benefit, even though the progression-free survival data was excellent. Some of the reasoning behind the lack of OS benefit I have postulated and reviewed include potentially a higher percentage of cancer patients with a disease-free interval after adjuvant therapy. Potentially also, the underpowered study with underestimation of the median overall survival for both arms of the study. And then and then there’s also that question remains. Whether all CDK 4/6 inhibitors are created equal. We are still waiting for the OS data from MONARCH 3, which is going to be presented at ESMO in a few weeks.
Key Points from the PALOMA-2 Clinical Trial For Hormone Receptor Positive Breast Cancer
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Confirmed diagnosis of estrogen receptor (ER) positive breast cancer cells
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PD-0332991 + Letrozole – PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
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Placebo + Letrozole – Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
ABCSG-18 study In Patients with Metastatic Breast Cancer
Another study presented at 2022 ASCO annual meeting that I’m excited to see what the data pans out, and, in terms of clinical practice, I would say right now, for the next few weeks, I’ll be using rival for our cancer patients care, who need to start on, see the start on first-line treatment for metastatic breast cancer research. If they don’t have any comorbidities or concurrent medications that will contradict Abemaciclib (aromatase inhibitors). But yeah, I would say for other patients, I would still use Palbociclib or then a cyclin first.
Then I presented another study looking at the use of Denosumab in the adjuvant setting for patients with early stage breast cancer and the secondary endpoint of DFS or disease-free survival in cancer patients. Yeah, disease-free survival. And then, that study was based on the ABCSG-18 study where Denosumab was used versus placebo in the adjuvant setting. The primary endpoint, which is the first time to fracture, reached a significant difference. This secondary endpoint with DFS and bone met recurrence survival, and the overall survival also was significant.
What is the Improvement For Cancer Patients Using Denosumab?
With improvement towards using Denosumab, that improved outcomes. So based on this, I would say the Denosumab adjuvantly can be considered and used. However, I think there is more data using Zometa adjuvantly compared to Denosumab. And I would still prefer using Zometa over Zoledronic Acid over the Denosumab.
KEYNOTE-522 Randomized Trial In Patients With TNBC (Early Stage Breast Cancer)
The study that I decided to look at next is triple-negative breast cancer in the early stage breast cancer setting. The analysis that was pre-planned looked at E-event free survival, EFS based on RCB residual (breast) cancer burden and what we found, and that was done within the KEYNOTE-522 study.
In clinical oncology ASCO 2022 KEYNOTE-522, which is a study looking at chemotherapy plus pembrolizumab, Neoadjuvantly versus chemotherapy, Neoadjuvantly lung followed by surgery, and then adjuvant pembrolizumab. That study reached its primary end goal of the time primary endpoint, which is PFS, with the improvement of PFS of their absolute improvement of 13%.
Then also the event-free survival. It shows the significant event, free survival improvement. The question remains who will benefit from pembrolizumab? And in that study, we saw that with the addition of pembrolizumab to chemotherapy, the residual (breast) cancers burden was reduced.
A much higher percentage of cancer patients have RCB 0 and 1, and less patients have RCB 2 and 3. What’s interesting, however, is that when you compare the subset of patients who reach RCB 0 and 1, the difference or the absolute benefit of pembro, additional to Pembrolizumab, is very small.
Why Are These Findings Not Significant?
It was not very significant. However, for cancer patients with higher residual burdens, such as RCB 2, there is a significant improvement in event-free survival for those patients. I think in our minds now. We still think that adding pembrolizumab until we know how to select our patients and adding pembrolizumab to neoadjuvant chemotherapy will be the standard of care.
There will be studies looking into whether adjuvant pembrolizumab is necessary for cancer patients with a pathologic complete response. And this question is going to be addressed in this S1418 study. And then also, how are we going to be able to select patients before treatment to give pembrolizumab who is going to reach the RCB 0 or past CR without pembrolizumab a question without exposing them to potential immune immunotherapy-related side effect? Yeah, so I think this is exciting.
The next study from 2022 ASCO annual meeting I decide to cover is HER-3 breast cancer in the era of novel ADCs (antibody drug conjugates). We are seeing more and more different types of targets that one can link to chemotherapy. HER-3 is one of the potential targets in breast cancer that can that we can target. HER-3 overexpressors and her three low breast cancer patients were enrolled from all subtypes onto the HER-3 ADC (antibody drug conjugates) study the phase 1 and 2 study using Patritumab Deruxtecan, and it was shown to have a very nice overall response rate of about 30% across all the. And then, the response duration is somewhere between 6 to 8 months. So, I think it’s respectable.
It may provide us with other treatment options for patients who run out of other options. So, I’m very happy to see that we are. Really in breast cancer, entering the era of antibody-drug conjugates (ADCs), and they can, different targets or antibodies can and potentially other ways to deliver the chemotherapy, like using nanoparticles, can lead us to a better outcome for our patients. Not just in overall survival but potentially curing. So, we don’t have to really face stage 4 breast for the majority of our patients in the future.
With that, I’m very happy to see some very excellent studying from 2022 ASCO annual meeting. I wish I could cover more abstracts, and many of them are excellent. There are excellent, but these are the abstracts that I think will currently practice changing findings and potentially practice-changing in the future.
Kay Yeung, MD, Ph.D., MOASC Breast Cancer Presentation
https://oncologytube.com/video/41294
Kay Yeung, MD, Ph.D., ASCO 2022 Breast Cancer Cancer Question & Answer
https://oncologytube.com/v/41314
Kay Yeung, MD, Ph.D. – About The Author, Credentials, and Affiliations
Her primary area of expertise is in the clinical oncology treatment of breast cancer patients, for which she holds board certification. In order to provide patients with the most effective range of treatment options, she employs a variety of therapeutic approaches, including as endocrine therapy, chemotherapy, targeted therapy, and immunotherapy.
She is also a teacher at the UC San Diego School of Medicine, where she is an associate professor of medicine, where she instructs medical school students, residents, and fellows. Dr. Yeung did both her residency in internal medicine and her hematology/oncology fellowship at the University of California, San Diego School of Medicine, where she also served as head fellow during her time there.