This video features Saba Shaikh, MD presenting on Disparities Research and Neoadjuvant. This presentation was given at our January 19th 21st Annual Highlights of the 2022 San Antonio Breast Cancer Symposium in 2023.
It is my pleasure to be talking about some of the oral presentations on disparities research and new attachment therapy. In this past year san Antonio breast conference. I have no disclosures. So we'll be talking about six presentations. Two will focus on breast cancer disparities, one on patient reported outcomes and three on new adjuvant therapy studies and her two negative breast cancer. So starting with health care disparities um specifically related to breast cancer. Something important to note that is that while black women have a 4% lower breast cancer incidents compared to white women, they have a 40% higher breast cancer mortality, a disparity that has remained stagnant for the past decade. This is a quote from the recently published cancer statistics from earlier this month. So the first study that we'll be talking about is race and clinical outcomes in the responder trial responder was a study that evaluated the utility of a 21 gene recurrence score. In patients that are hormone positive. Um With 123 lymph nodes, patients with recurrent score of 0 to 25 were randomized to receive chemotherapy followed by endocrine therapy for endocrine therapy alone. These data have been previously presented and published but here they report clinical pathologic characteristics, survival outcomes and race in association with recurrence score. So, um this is the breakdown of the self reported racial groups in this in this study with 70% of these patients being white and 6.1% being black, 18% of these patients were excluded due to unreported race. Native American Pacific Islander patients were excluded due to small number of patients and there were 15% of patients were Hispanic and 8% of patients were Asian. Something to keep in mind is that the black patients were underrepresented in this trial at 6%. Compared to the 2021 census data, which reports about a 13.6% population of black patients in the United States. They found that recurrent score distribution was actually similar across the racial groups. And one interesting finding they reported is that premenopausal black patients were less likely to receive and recycling based chemotherapy. This difference was not noticed in postmenopausal patients and it's unclear why this may have been. Black patients also had a decreased five year I. D. F. S. Of 87.2%. In comparison to white patients at 91.5% black patients were more likely though to accept treatment arm and had equivalent endocrine therapy adherence at both six and 12 months. So this may not be a reason to explain the difference that we're seeing in I. D. F. S. So in summary recurrence risk distribution was similar across the different racial groups. Premenopausal black patients were less likely to receive and recycling chemotherapy reasons for which are unknown. Black patients have a decreased five year I. BFFs. Even when adjusted for recurrent score treatment armed menopausal status, age and grade and black patients are more likely to accept treatment assignment and had equivalent adherence to endocrine therapy at six and 12 months. In the study, moving on to some racial disparities that may have been noted in relation to the tumor micro environment. This group chose to focus specifically on team M doorways for tumor micro environment of metastases doorways. These are comprised of tumor cells, macrophages and endothelial cells and it can lead to vascular openings that allows for dissemination of cancer cells. The group chose to focus on this because there was previously published data that the components of TMM doorways maybe increase in black patients in comparison to white patients. TMM score has also previously been shown to correlate with risk of distant metastases and hormone positive breast cancer. And mouse models have suggested use of neo adjuvant chemotherapy may actually increase team M doorway score and metastases. So in this study they evaluated patients with her two negative breast cancer who had residual disease of at least five millimeters. After receiving neo adjuvant chemotherapy, they then calculated a TMM doorway score on the residual disease. They had 96 black patients in 87 white patients. And these patients were further subdivided based on hormone positive and triple negative disease. They found that black patients were more likely in this study to have distant recurrences and higher grade tumors. They also notably had an increase in mastectomy in comparison to breast conservation therapy. Other features such as time to distant recurrence tumor stage lymph node status subtype were similar between the patients. They found an increase in the team m doorway score overall. And this was really driven by the hormone positive patients. And they reported that a high team M doorway score was associated with worse D. R. F. S. And hormone positive disease. So in summary, there was an increased TMM doorway score reported in black patients with hormone positive disease with residual disease after chemotherapy. However, no baseline team M score was reported in the study to assess if this changes related to me to receive of neo adjuvant chemotherapy, racial disparities may partially be attributed to differences in tumor micro environment. And this needs to be evaluated further with additional incorporation of social determinants of health factors will now be moving on to patient reported cognitive impairment and women participating in the responders study. So we previously discussed the scheme of the responder trial and this is a patient reported outcome sub study within the responders study. So in this study, over 500 patients responded to a health-related quality of life questionnaire that was obtained at baseline six months, 12 months and 36 months. They used the promised cognitive function concerns, which allowed patients to score statements from 0-4. These statements included things like my thinking has been slow. I've had trouble concentrating. I've had to work harder than usual to keep track of what I was doing and other similar statements. There were 139 premenopausal patients and their baseline characteristics are reported here and there were 429 postmenopausal postmenopausal patients included in the study. What they found is that in the pre menopausal patients in the patients who received chemotherapy followed by endocrine therapy, denoted here by the blue line. There was a decrease in self reported cognitive function at six months and 12 months. This improved slightly by 36 months but it did not return to baseline with endocrine therapy. There was also a decrease at six months and 12 months, although not to such a degree that we see with the chemotherapy arm And then by 36 months the patients did um report that their cognitive function was was back to baseline In the post menopausal arm, interestingly there's no change in cognitive functions for with endocrine therapy. But in the chemotherapy followed by endocrine therapy group there was a decrease at six months and 12 months and at 36 months while there was some improvement, it did not return back to baseline. So in summary in premenopausal patients, endocrine therapy and chemotherapy both reduced self reported cognitive impairment at six and 12 months. In premenopausal patients. Self reported cognitive function returns to baseline with endocrine therapy but not chemotherapy at 36 months. In postmenopausal patients scheme Therapy but not endocrine therapy reduces self reported cognitive impairment and does not return to baseline at 36 months. This is something interesting that we should continue to study and these data can be something we reflect upon when we when we discuss these kinds of side effects with our patients receiving such their treatments. Now I'll be moving on to the new adjuvant therapy portion of this um presentation will be starting with the phase a randomized phase three trial that looked at the addition of platinum to sequential taxing and recycling neo adjuvant chemotherapy in patients with triple negative breast cancer. So this is a phase three randomized trial that in that included patients with triple negative breast cancer. They used a 1% cut off for er and pr and they were randomized to receive either paclitaxel followed by A. C. Or D. C. Or paclitaxel plus carbo platinum followed by A. C. Or E. C. They then received definitive therapy as indicated with surgery and radiation. Um and this and the primary endpoint was event free survival. And that's what the study was powered for. With a total number of 720 patients. The secondary endpoints included Os and Patsy are rates the patients were stratified by menopausal status. The patient characteristics are noted here and some important things to note are that um about 68-70% of these patients were less than 50 years old and 57 58% of these patients were pre or peri menopause. This was a quite an advanced patient population with 60% of these patients having a clinical T. Four and two and three disease, 89% of these patients were known positive, and 77% of these patients had a tumor size greater than five centimeters In the overall intention to treat population. Pathological complete response rate increased with Carbo platon from 40% to 54%. However, when they further evaluated this based on age greater than and less than 50, they found that this benefit was solely driven by the patients who were less than or equal to 50. Um their increase in pathologic complete response rate with cargo platon went from 41% to 61%, whereas in the patients that were greater than 50 had virtually no improvement in path cr eight with cargo platon. While the overall PFS benefit had a trend um had a trend to improvement, although it was not statistically significant. There was an eF. S benefit noted in the patients were less than 50. Um interestingly, and not surprisingly, we saw in this study that the patients who had a pathologic complete response rate had an improvement in E. F. S. In comparison to the patients who did not have a pathological response. There was also increased overall survival reported in the intention to treat population, which was largely driven by the patients who were under the age of 50. The adverse events were comparable except for that there was an increase in human to logic. Side effects such as neutropenia, anemia anemia and neutropenia fever in the cargo platinum with the weekly carbon platte inducing. Uh there was um comparable completion of the neo adjuvant chemotherapy in both the carbon Platten and control arms. So in summary in this patient population, 88% of patients who are not positive and 60% of patients were clinically T four and two or N three. The addition of carbon Platten increased paths er DFS and OS in patients were less than or equal to 50 but not patients were greater than 50 years. I think this is practice changing for some and perhaps practice reaffirming for others right now. The current standard of care for patient populations such as this would be based on the keynote 5 to 2 regimen which include A. C. T. C. Plus Pemberley is a map. However, there may be patients who are not candidates for immune checkpoint inhibitors and I think this trial really um highlights the benefit of carbon Platten especially in patients who are younger than 50. And this study um notably was powered for a long term outcomes such as the F. S. We also see an increased grade three neutropenia anemia thrombosis, a pina neutropenia fevers with carbon Platten but otherwise the side effects were pretty comparable and there was reasonable completion of the chemotherapy in both arms. One thing to note is that brock a mutation status was unknown due to availability of testing at the time of study initiation which was in 2010. Well that will be moving on to get parola which um is a randomized phase two trial evaluating neo agimat paclitaxel. An elaborate in comparison to paclitaxel carbo. Platinum patients with her two negative and homologous recombination deficiency. So this is a randomized phase two study looking at her two negative patients who are H. R. D. This is defined as somatic or germline BRCA one or two mutations or a high hrd score which was defined as a my choice score of 42 or greater patients were randomized to receive paclitaxel with the addition of elaborate 100 mg twice daily. This lower dose was selected to improve tolerable itty. This was then followed by E. C. Or the other arm was weekly paclitaxel with weekly cargo plot in A. U. C. Which was then followed by ec patients then went on to receive surgery and the primary endpoint was pathologic complete response. The secondary endpoint include breast conservation rate. Clinical and imaging response. Tolerable. Itty and safety. One key patient characteristic to note that was not balanced between the two arms is the clinical node positivity rate which was higher in the cargo Platen arm compared to the elaborate arm They previously reported the Patsy R. A. In the two arms which were reported to be um similar 55% with the in the elaborate arm and 48% in the cargo platon arm. They then looked at path CRE by Bracha status and in patients who had a germline or somatic BRCA mutation there was a 60% path C. R. A. With both the elaborate farm and the carbo platinum. But in patients who were Bracha wild type while there was a 50% path C. R. A. And the elaborate farm there was a 37.5% path cR rate. In the cargo platinum idea fest in the overall population was inferior with elaborate. However, when they stratified by brock a mutation status, they found that idea fest was similar with elaborate and carbo platon and patients who had a germline or somatic BRCA mutation in patients who were broccoli wild type. Again, we see inferiority with elaborate in comparison to the cargo platon arm, D. D. F. S. And O. S. In the overall population. Again, in both these outcomes shows that elaborate was inferior to carbo platinum in the overall population. So in summary, I DFS DFS and Os were overall inferior with elaborate and Taxol followed by ec. In comparison to carbo platinum. Taxol followed by Ec. However, I DFS was comparable between elaborate and carbo platinum arms in the back. A mutant patients whether that be german or somatic. However something to keep in mind that this was a small sample size. So this is not something that's ready for clinical practice yet but certainly intriguing data that would warrant further evaluation. The last of the Neo Assyrian studies that I'd like to discuss is from the new a German spy to trial. Looking at the combination of some diplomat with Regeneron 37 67. In addition to new adjuvant chemotherapy. Regeneron 37 67 is a lag three antagonist which is a more relatively novel immune checkpoint. Um There are other laG three inhibitors such as which have now been FDA approved for use in metastatic melanoma. Some diplomat is an anti PD one agent that is more commonly used in non small cell lung cancer and cutaneous squamous cell carcinoma. So I Spy two is a multi center adaptive randomization. Phase two platform trial which randomizes patients either to the control arm which at this time was paclitaxel weekly times 12 or to one of the investigational arms. The arm that we're talking about today is paclitaxel plus Regeneron 37 67 plus the mental map. These patients all then receive a C. And this is followed by surgery with the primary endpoint of paths er as you can see there is a lot of biomarker analysis in this study with imaging tissue and blood analysis In this study. If the agents are then um found to have an 85% predicted probability of success in a 300 patient. Phase three New American trial. The agent is then graduated Regeneron and in this study were dosed every three weeks for four doses and Paclitaxel was weekly times 12 weeks. Some patient characteristics to note 50, a little over a little over 50% of the patients were hormone positive. The mean tumor size was 3.4 in the Regeneron arm and 3.8 in the control arm. And about 40% of these patients were known positive. The addition of simple mob and Regeneron 37 67 to neo adjuvant chemotherapy increased the RCB 01 rate in both the triple negative and hormone positive cohorts in triple negative. We see an increase from 48% to 70% and then hormone positive. We see an increase from 29% to 60%. Some diplomats and regeneration 37 67. In addition to tax, all followed by a C graduates based on predictive probability of success of 91 to 95% in the phase three trial. This was based on estimated path cr rate um that increased With the combination in comparison to control. In the her two negative population that was 44% compared to 21%. In the triple negative population, 53% compared to 29%. And in the hormone receptor positive population, 36% to 14%. There was no increase in non immune grade three adverse events. There was an increase in all great events such as anemia diarrhea peripheral neuropathy among some other adverse events which are listed here. Of note, 53% of patients experience an immune related adverse event. But there were no great for events. The most common immune related adverse events were hypothyroidism and adrenal insufficiency and most events occurred after 12 weeks with some as late as 3 to 6 months post op. And this is you know, comparable to what we've seen in some other immune checkpoint inhibitor trials where there can be some delayed immune related adverse events. They also looked at I am imprint which is a 53 gene signature. Uh this was derived from patients treated on ice by two and it's developed to predict responses to immunotherapy and hormone positive and triple negative breast cancer. So 40% of the patients with triple negative breast cancer were deemed to be immune positive and 28% of the hormone positive patients were deemed to be immune positive. Of note the path the pathologic complete response rate is significantly elevated in the immune positive group with when they received immune checkpoint inhibitors, 82% compared to 35% in triple negative and 91% compared to 33% and hormone positive. So in summary, simple mob anti Pd one and Regeneron 37 67 anti lag three increased RCB 01 rate in both triple negative and hormone positive breast cancer imprint identifies benefit from immune checkpoint inhibitors and needs to be prospectively validated in a larger sample size which would be of great interest. Approximately half of the patients treated with and Regeneron 37, experienced an immune related adverse event which is why future studies will evaluate a lower dose of Regeneron 37 67. So, in the interest of time, I won't go through the, you know, the summary of all these presentations that we discussed today. But I think the key takeaway is that there's a lot of interesting work being done in breast cancer disparities, patient reported outcomes As well as new adjuvant therapies. And I think the one that is something that we can continue to incorporate in the clinical in the clinical setting is the use of carbon Platten in the neo adjuvant setting in patients with her two negative breast cancer. Um we're also hormone negative and especially those who are less than 50 years old. Thank you.
