Sarah Cannon

Howard A. “Skip” Burris, III, MD, FASCO, FACP, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 Giant of Cancer Care® in Drug Development, discusses using biomarkers to determine the benefits of immunotherapy and chemotherapy in triple-negative breast cancer (TNBC).

In the phase 3 IMpassion130 trial, investigators are examining atezolizumab (Tecentriq) in combination with paclitaxel in patients with TNBC. The biomarkers used in this study are helping the field to understand which patients might benefit from immunotherapy plus chemotherapy, says Burris.

There are now several opportunities to think about PD-L1 overexpression, tumor mutational burden, and microsatellite instability in this setting; this brings up the idea of cell death. It is known that chemotherapy works fairly well in TNBC, although adverse effects and how long the combination therapy can be administered are questions that still need to be addressed, concludes Burris. 

Videos

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses using biomarkers to determine the benefits of immunotherapy and chemotherapy in triple-negative breast cancer.

Dr. Burris on Predictive Biomarkers for Chemoimmunotherapy in TNBC

A multidisciplinary approach is needed to improve the delivery and quality of care for patients with stage III/IV non–small cell lung cancer (NSCLC), according to David R. Spigel, MD, and results from a comprehensive, double-blind survey have helped to inform criteria for ideal care.

The objective of the Fostering Excellence in Care and Outcomes in Patients with Stage III and IV NSCLC initiative was to examine the benefits of lung cancer care with a multidisciplinary team, assess and quantify practitioners’ understanding of evolving standards in diagnosis and treatment of the disease, determine and overcome obstacles to care, and to explore process improvement models.

In order to provide cohesive care, multidisciplinary collaboration is needed, according to Spigel. Through Association of Community Cancer Centers (ACCC) leadership, a steering committee was created; this committee ultimately decided the different elements that would be incorporated into the comprehensive, double-blind survey. Responses were received from 639 participants affiliated with 160 cancer programs across the United States.

Preliminary data from the survey were reported during the 

. Results revealed that 41% of participants (n = 261) indicated that their cancer program did not have a thoracic multidisciplinary clinic.

 He also explained that nurse navigators (

 = .04) were at higher likelihood to engage in shared decision-making practices compared with other disciplines. The most prominent barriers to care included a lack of community awareness, patient interest, and transportation.

The steering committee also worked together to compile evidence-based recommendations on how to provide ideal care for this population. Recommendations included a multidisciplinary evaluation of suspicious findings, multidisciplinary coordination for effective biopsy collection, and the use of expansive molecular profiling to identify rare mutations

“You can see that the power of committing to providing some information and then collecting that at a broad level could provide really valuable information to effect care not only in the United States but potentially globally,” said Spigel, chief scientific officer, director of the Lung Cancer Research Program, and principal investigator at Sarah Cannon Research Institute.

, Spigel discussed the Fostering Excellence in Care and Outcomes in Patients with Stage III and IV NSCLC initiative, analyzed the survey data, and next steps for the research.

: Could you provide some background on the initiative?

: This effort was designed to look at how we manage [patients with] stage III and stage IV lung cancer in the community, specifically with a focus on multidisciplinary conferences. The management of lung cancer, especially for stage III disease, really involves different disciplines of care beyond just medical oncology [to work together]; radiation oncologists, surgeons, pathologists, or pulmonologists, [should be included]. Bearing this in mind, [it’s important to] have tumor boards or multidisciplinary tumor conferences.

Are these meetings happening routinely in centers in the community? Are they happening at academic centers? How does they happen? What happens at those meetings? Do we believe care is impacted by whether they happen or not? Are these meetings being done well or could they be improved? The whole idea here was to look into this further. The ACCC objective was to collect information from those who take care of patients with lung cancer, measure what is actually happening, and then use that knowledge to affect change.

Prior to conducting the survey, what were the primary barriers to cohesive care in those community and academic settings?

To be honest, a lot of this hinges on the time it takes to get busy clinicians together to meet. In fact, it's amazing this all happened before [the] COVID-19 [pandemic] because, although our meetings are now all virtual, it's a little bit different when you're in a room together and you can have conversations more easily. Honestly, time is the perceived biggest barrier, but usually there are solutions to those challenges.

There's great motivation and interest to meet and improve on patient care. There's a desire to have the comfort of other clinicians and colleagues to validate your care choices. It's not that ego is preventing [us from] getting together. [There is no], ‘I know how to do things better than anyone else and so I don't need any help.’ It's more, ‘How do we do this? How do we practically get together in a regular cadence that works for everyone?’

Through ACCC’s leadership, a steering committee was created to discuss the kinds of elements that we want to include in a survey; I was part of that committee. Then, with the help of many individuals, nearly 1200 surveys were sent out across the country. What ended up getting just under 640 responses affiliated with 160 unique cancer programs across 44 US states that were suitable for analysis.

We had different disciplines that responded—again, it wasn't just medical oncologists; it was really anyone [involved in] lung cancer care at 1 of these centers who could respond. Then, we collected information and were able to parse out the different disciplines, their responses, and see how those vary.

Two abstracts were presented at the 2020 ASCO Virtual Scientific Program based on these findings. How did they inform the recommendations?

There's still a lot of analysis [to be done]. Just under half of respondents, so about 41%, indicated that their center did not have a thoracic multidisciplinary clinic. We were all surprised to see that the number was so high. That's not to say things don't happen that involve different colleagues in the care of a patient at those centers, but in terms of a formal, multidisciplinary clinic, that was a pretty high number. When you think about disciplines involved in care and who is most involved in terms of that shared decision-making, a couple of [insights] have emerged.

One is that not every program has a nurse navigator; this is an individual who helps shepherd that patient's care through these different points of contact. Not surprisingly, in those centers that had nurse navigators, these individuals were found to be among the most engaged disciplines involved in that shared decision-making process. The lesson there is that every center should have a nurse navigator because they will be the most engaged.

The other, [which is] a little bit of surprise, were radiation oncologists. Radiation oncologists seemed to be among the most likely groups to be involved in shared decision-making. Often, patients with stage III lung cancer present to other disciplines, such as thoracic surgeons or medical oncologists. Having those patients present and then getting them referred to a radiation oncologist involves a lot of communication. It's gratifying to see that our radiation oncology colleagues are among the most engaged and involved in that shared decision-making process. Understanding what your medical oncologist wants to do, how they are doing it, and how they’ll start [is essential]. Coordinating that care in terms of when you're starting radiation therapy, either around chemotherapy or even around surgery, is critical and that was reflected in the data.

Could you expand on the significance of nurse navigators in this setting?

I wish we had a nurse navigator for every patient who had cancer just because our system can be quite complex. If you think about stage III cancer and all of those involved in a patient's journey through that care, it can be overwhelming. Not to mention, if a patient needs to go to different centers or places in the community to meet a radiation oncologist and medical oncologist, get a biopsy done, and have an interview with a surgeon—that can be overwhelming. That's probably more so in a community setting than in an academic center, where everything tends to be centralized. Having a navigator to help [a patient] get from A to B to C is invaluable.

The most exciting part of this whole project is first collecting information and, as I said, tthere is a lot to learn with the potential to dive [deeper] into [certain] areas. However, the next major objective—and we're in the middle of this now—is trying to affect change, so to take learnings about what centers have and don't have in terms of best practices, and then focusing in on a handful of those centers and working in-depth on specific issues. For example, we can tackle something like molecular testing, [work on] understanding how it is done at your center, as well as the barriers to getting that done, and what we see as a group [in terms of] potential solutions. How do we take a problem, come to some agreement on what the barriers are to fix that problem, and then attack and solve that problem.

At a broader level, how can we learn what works well from the survey, what doesn't work well, and then convert that into a standard best practice, and put that into action? We haven't really leapt that far ahead yet but I could imagine measuring those results. Could you affect change that leads to better outcomes for patients? Could you package that all up and kind of widely distribute that? That's what's exciting: learning from ourselves, learning from each other, and then applying best practices to improve the lives of all our patients with cancer, or in this specific case, lung cancer.

Is there anything else that you wanted to highlight?

Lung cancer care is moving so fast, with new therapies approved and new approaches in early-stage disease, but we anticipate even [more developments]. Coming together and educating each other about these rapid changes can be the best way to translate what's being discovered in the laboratory to the clinic.

Association of Community Cancer Centers releases preliminary findings from survey on advanced non-small cell lung cancer care. News release. Association of Community Cancer Centers. June 18, 2020. Accessed July 13, 2020. https://bit.ly/33rfQw2.

Salgia R, Boehmer L, Celestin C. Improving care for patients with stage III/IV NSCLC: Learnings for multidisciplinary teams from the ACCC national quality survey. 

. 2020;38(suppl 15):e19195. doi:10.1200/JCO.2020.38.15_suppl.e19195

Socinski MA, Boehmer L. What constitutes high-quality NSCLC care? Overarching quality considerations for improving NSCLC care at US cancer centers. 

. 2020;38(suppl 15):e19181. doi:10.1200/JCO.2020.38.15_suppl.e19181

Articles

David R. Spigel, MD, discusses the Fostering Excellence in Care and Outcomes in Patients with Stage III and IV NSCLC initiative, analyzes the survey data, and next steps for the research.

Multidisciplinary Collaboration Needed to Provide Cohesive Care in Advanced NSCLC

Institutional Perspectives in Cancer (IPC)

. These virtual events assemble academic and community-based physicians and healthcare professionals across key disciplines from medical and surgical oncology. Specialist experts serve as faculty for these premier and renowned oncology webinars, which focus on the most relevant cancer topics to ultimately improve patient care. Registration for this virtual event is complimentary.

Join us for an Institutional Perspectives in Cancer webinar on Thursday, August 13, 2020 featuring Erika P. Hamilton, MD.

Breast Cancer Chaired by Erika P. Hamilton, MD

Jesus G. Berdeja, MD, the director of Multiple Myeloma Research at Sarah Cannon Research Institute, discusses updated safety results from the ongoing phase 1b/2 CARTITUDE-1 trial (NCT03548207) with the CAR T-cell therapy JNJ-4528 in multiple myeloma.

In the study, neurotoxicity was rare; only 1 patient reported an event that was grade 3 or higher in severity, Berdeja says. Significant cytopenias were also observed with JNJ-4528, including neutropenia and thrombocytopenia, although most events resolved within 60 days, says Berdeja. All-grade upper respiratory tract infections were reported in 31% of the patients, however, none of these infections were unexpected, adds Berdeja.

Additionally, results showed a 100% overall response rate with the product, which included a stringent complete response rate of 86% and very good partial response rate of 97% at a median follow-up of 11.5 months, explains Berdeja.

Finally, 16 patients with a CR achieved minimal residual disease (MRD)–negative disease status. Of those patients, 81% were MRD negative at 10-5 or better and 69% were MRD negative at 10-6. The estimated progression-free survival rate at 9 months was 86%, concludes Berdeja.

Jesus G. Berdeja, MD, discusses updated safety results from the ongoing phase 1b/2 CARTITUDE-1 trial (NCT03548207) with the CAR T-cell therapy JNJ-4528 in multiple myeloma.

Dr. Berdeja on Updated CARTITUDE-1 Results With JNJ-4258 in Multiple Myeloma

Stephanie L. Graff, MD, director of the Breast Program at the Sarah Cannon Cancer Institute of HCA Midwest Health and associate director of the Breast Cancer Research Program at Sarah Cannon Research Institute, discusses future research with immunotherapy in breast cancer.

Estrogen receptor–positive breast cancer has not been an area where immunotherapy is often considered, says Graff. However, the earlier patients who have other subtypes, such as triple-negative or HER2-positive disease are treated with this approach, the more robust their response will be, adds Graff.

Future trials should examine immunotherapy in carefully selected patients with hormone receptor–positive disease, says Graff. Going forward, efforts should focus on understanding how other genetic and genomic risk profiles impact treatment decisions, and likely other lines of therapy will be moved up into the earlier-phase setting, concludes Graff.

Stephanie L. Graff, MD, discusses future research with immunotherapy in breast cancer.

Dr. Graff on Future Research With Immunotherapy in Breast Cancer

Ian W. Flinn, MD, PhD, director of the Blood Cancer Research Program, Sarah Cannon Research Institute, discusses the role of BTK inhibitors in chronic lymphocytic leukemia (CLL).

BTK inhibitors such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) have been transformative in the treatment of patients with B-cell malignancies such as CLL, mantle cell lymphoma, marginal zone lymphoma, and Waldenström's macroglobulinemia, says Flinn.

In CLL specifically, BTK inhibitors have become a prominent frontline standard of care, adds Flinn.

Though, it is important to acknowledge that the toxicities that are associated with ibrutinib, including arthralgias, atrial fibrillation, and, though rare, significant bleeding, often lead to treatment discontinuation in patients with CLL.

Ian W. Flinn, MD, PhD, discusses the role of BTK inhibitors in chronic lymphocytic leukemia.

Dr. Flinn on the Role of BTK Inhibitors in CLL

 On Air! I’m your host today, Caroline Seymour

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Howard A. "Skip" Burris, III, MD, FASCO, FACP, and Stephanie L. Graff, MD, both of Sarah Cannon Research Institute, to discuss the impact of COVID-19 on patients with breast cancer, the transition to telemedicine, the protocols their institution has put into place to reduce potential exposure to the virus, and some of the work HCA Midwest Health has been a part of regarding COVID-19 prevention and management.

Additionally, Dr. Burris and Dr. Graff shared some of the resources released by the American Society of Clinical Oncology (ASCO) for patients during the COVID-19 pandemic, explained how the society has leveraged its platform to help reestablish cancer care and research, and discussed the ultimate decision to make the 2020 ASCO Annual Meeting virtual.

In our exclusive interview, Dr. Burris, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 

 in Drug Development, and Dr. Graff, director of the Breast Program at the Sarah Cannon Cancer Institute of HCA Midwest Health and associate director of the Breast Cancer Research Program at Sarah Cannon Research Institute, discussed how the pandemic has affected cancer care, the collaborative efforts made between Sarah Cannon and HCA to increase access to investigational COVID-19 treatments, and the steps ASCO has taken to ensure its members’ professional education and well-being during this time.

Podcasts

Howard A. "Skip" Burris, III, MD, FASCO, FACP, and Stephanie L. Graff, MD, discuss how the COVID-19 pandemic has affected cancer care, the collaborative efforts made between Sarah Cannon Research Institute and HCA to increase access to investigational COVID-19 treatments, and the steps ASCO has taken to ensure its members’ professional education and well-being during this time.

Dr. Burris and Dr. Graff Talk COVID-19 and Cancer Care, Telemedicine, and ASCO Initiatives

Therapeutic options for pretreated HER2-positive breast cancer now include tucatinib (Tukysa) as part of a triplet regimen with a tolerable safety profile that promises improved quality of life.

On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for adults with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least 1 prior anti—HER2-based regimen in the metastatic setting. Tucatinib is a HER2-directed tyrosine kinase inhibitor.

The approval is based on findings from the phase 2 HER2CLIMB study (NCT02614794), which demonstrated the triplet’s capacity to improve survival in patients with and without brain metastases. In the overall population, the median progression-free survival (PFS) with the 3-agent approach was 7.8 months versus 5.6 months with trastuzumab and capecitabine alone. Among those with brain metastases, median PFS was 7.6 months in the tucatinib arm versus 5.4 months in the control group.

, Erika P. Hamilton, MD, director of the Breast Cancer and Gynecologic Research Program at Sarah Cannon Research Institute in Nashville, Tennessee, discussed the regimen’s potential in earlier lines of therapy and how HER2CLIMB’s inclusion of patients with brain metastases has the power to move the needle in clinical investigations of therapies in this subgroup.

What was noteworthy about the efficacy data?

HER2CLIMB had 4 end points looking at progression-free survival, overall survival, overall response rate, and then progression-free survival among patients with brain metastases. The trial met all 4 of these end points, so it was a win across the board.

The activity in the population of patients with brain metastases really stood out. We have a lot of good therapies for breast cancer, but many of them do not cross the blood-brain barrier, so patients with brain metastases comprise a very highrisk patient population that is known to have worse outcomes. To have a drug that not only [meets end points] across the board but also benefits patients with brain metastases is meaningful. There is a statistic from the trial that [shows] the progression-free survival at 1 year among patients with brain metastases was 0% if they were not receiving tucatinib [compared with] a quarter of patients with brain metastases who remained on the trial at 1 year and were [receiving tucatinib].

Why is HER2CLIMB’s inclusion of a broad population of patients with brain metastases important?

In oncology trials, we commonly allow patients with brain metastases only if they have been treated with local therapy, such as resection or radiation and are stable 4 weeks after they finish local treatment. This trial was very different. HER2CLIMB allowed 3 different populations of patients with brain metastases to enroll: this traditional population with stable, pretreated brain metastases; metastases that had never been treated; and metastases that were treated and had progressed after. It was a very high-risk population.

Right now, I think that there is a lot of talk about how important clinical trials are and many patients’ trouble accessing them. We know that the best treatment option for a patient is enrolling on a clinical trial. There is also a lot of talk about how our inclusion criteria are a little too [strict], maybe [stricter] than they need to be, and historically, there has been some fear from drug companies because they do not want to include patients who may be sicker, not have optimal organ function, or in this case, have actively progressing brain metastases and may not do as well on therapy.

I think it was progressive, wise, and brave to allow these patients on the trial, who probably stood to benefit the most. After this trial, because it is the first one to do so, I think there will be many more companies who will follow suit.

How well is the tucatinib triplet regimen tolerated?

We normally give HER2 therapy in conjunction with chemotherapy. Capecitabine is an oral chemotherapy that tends to be pretty well tolerated. It does not cause hair loss, and it also does not cause a patient’s [white blood cell] counts to drop [significantly], so it is a favored chemotherapy partner in breast cancer. Trastuzumab is our most widely used HER2 antibody, and we learned that having a dual HER2 blockade such as trastuzumab with pertuzumab [Perjeta] or in this case, trastuzumab and tucatinib, can [lead to] additive [efficacy]. It is a very good combination, and I think that what is unique about tucatinib is this [agent] does not add a whole lot of toxicity.

The most common adverse events we saw in the trial were diarrhea, hand-foot syndrome, nausea, and fatigue, and those are the most common side events of capecitabine as a single agent. The addition of tucatinib added some liver dysfunction, about a 5% grade 3 elevation in liver function tests that was reversible.

The most important [characteristic] of tucatinib that is unlike other HER2 [agents] that we are familiar with like lapatinib [Tykerb] and neratinib [Nerylnx] is that tucatinib is specific and only blocks HER2, which makes it better tolerated than some of our more traditional options for HER2-positive breast cancer. Lapatinib and neratinib not only block HER2, but they also block HER1, or EGFR, and toxicities of rash and diarrhea come from EGFR [inhibition].

What are the next steps for the use of this regimen?

Can we move tucatinib earlier [in the treatment paradigm]? There is a lot of excitement around the brain metastases data, but I do not see this as a drug that I would only use in patients with brain metastases because it is an active regimen for the 52% of patients on the trial who did not have brain metastases. Because our systemic therapies are effective for HER2-positive breast cancer, these women are living longer and longer. Up to 50% of people with this disease will eventually develop brain metastases, which is quite a bit higher than some other types of cancer, so using a drug like tucatinib, even in the absence of brain metastases—that can get into the brain and work&mdash;may prevent brain metastases. I think an important question to ask moving forward is if we use tucatinib earlier, could we prevent brain metastases?

Figure. Tucatinib in Combination With Trastuzumab and Capecitabine (Click to Enlarge)

I am currently enrolling [patients in] the HER2CLIMB-02 trial [NCT03975647] of tucatinib in combination with T-DM1 [Kadcyla; ado-trastuzumab emtansine] or T-DM1 alone in the second-line setting.

Tucatinib Approval Adds Impact to HER2+ Breast Cancer Paradigm

Therapeutic options for pretreated HER2-positive breast cancer now include tucatinib (Tukysa) as part of a triplet regimen with a tolerable safety profile that promises improved quality of life.

On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for adults with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least 1 prior anti–HER2-based regimen in the metastatic setting. Tucatinib is a HER2-directed tyrosine kinase inhibitor.

The approval is based on findings from the phase 2 HER2CLIMB study (NCT02614794), which demonstrated the triplet’s capacity to improve survival in patients with and without brain metastases. In the overall population, the median progression-free survival (PFS) with the 3-agent approach was 7.8 months versus 5.6 months with trastuzumab and capecitabine alone. Among those with brain metastases, median PFS was 7.6 months in the tucatinib arm versus 5.4 months in the control group.

In an interview with 

®, Erika P. Hamilton, MD, director of the Breast Cancer and Gynecologic Research Program at Sarah Cannon Research Institute in Nashville, Tennessee, discussed the regimen’s potential in earlier lines of therapy and how HER2CLIMB’s inclusion of patients with brain metastases has the power to move the needle in clinical investigations of therapies in this subgroup.



HER2CLIMB had 4 end points looking at progression-free survival, overall survival, overall response rate, and then progression-free survival among patients with brain metastases. The trial met all 4 of these end points, so it was a win across the board.

The activity in the population of patients with brain metastases really stood out. We have a lot of good therapies for breast cancer, but many of them do not cross the blood-brain barrier, so patients with brain metastases comprise a very highrisk patient population that is known to have worse outcomes. To have a drug that not only [meets end points] across the board but also benefits patients with brain metastases is meaningful. There is a statistic from the trial that [shows] the progression-free survival at 1 year among patients with brain metastases was 0% if they were not receiving tucatinib [compared with] a quarter of patients with brain metastases who remained on the trial at 1 year and were [receiving tucatinib].





In oncology trials, we commonly allow patients with brain metastases only if they have been treated with local therapy, such as resection or radiation and are stable 4 weeks after they finish local treatment. This trial was very different. HER2CLIMB allowed 3 different populations of patients with brain metastases to enroll: this traditional population with stable, pretreated brain metastases; metastases that had never been treated; and metastases that were treated and had progressed after. It was a very high-risk population.

Right now, I think that there is a lot of talk about how important clinical trials are and many patients’ trouble accessing them. We know that the best treatment option for a patient is enrolling on a clinical trial. There is also a lot of talk about how our inclusion criteria are a little too [strict], maybe [stricter] than they need to be, and historically, there has been some fear from drug companies because they do not want to include patients who may be sicker, not have optimal organ function, or in this case, have actively progressing brain metastases and may not do as well on therapy.

I think it was progressive, wise, and brave to allow these patients on the trial, who probably stood to benefit the most. After this trial, because it is the first one to do so, I think there will be many more companies who will follow suit.





We normally give HER2 therapy in conjunction with chemotherapy. Capecitabine is an oral chemotherapy that tends to be pretty well tolerated. It does not cause hair loss, and it also does not cause a patient’s [white blood cell] counts to drop [significantly], so it is a favored chemotherapy partner in breast cancer. Trastuzumab is our most widely used HER2 antibody, and we learned that having a dual HER2 blockade such as trastuzumab with pertuzumab [Perjeta] or in this case, trastuzumab and tucatinib, can [lead to] additive [efficacy]. It is a very good combination, and I think that what is unique about tucatinib is this [agent] does not add a whole lot of toxicity.

The most common adverse events we saw in the trial were diarrhea, hand-foot syndrome, nausea, and fatigue, and those are the most common side events of capecitabine as a single agent. The addition of tucatinib added some liver dysfunction, about a 5% grade 3 elevation in liver function tests that was reversible.

The most important [characteristic] of tucatinib that is unlike other HER2 [agents] that we are familiar with like lapatinib [Tykerb] and neratinib [Nerylnx] is that tucatinib is specific and only blocks HER2, which makes it better tolerated than some of our more traditional options for HER2-positive breast cancer. Lapatinib and neratinib not only block HER2, but they also block HER1, or EGFR, and toxicities of rash and diarrhea come from EGFR [inhibition].





Can we move tucatinib earlier [in the treatment paradigm]? There is a lot of excitement around the brain metastases data, but I do not see this as a drug that I would only use in patients with brain metastases because it is an active regimen for the 52% of patients on the trial who did not have brain metastases. Because our systemic therapies are effective for HER2-positive breast cancer, these women are living longer and longer. Up to 50% of people with this disease will eventually develop brain metastases, which is quite a bit higher than some other types of cancer, so using a drug like tucatinib, even in the absence of brain metastases—that can get into the brain and work—may prevent brain metastases. I think an important question to ask moving forward is if we use tucatinib earlier, could we prevent brain metastases?

I am currently enrolling [patients in] the HER2CLIMB-02 trial [NCT03975647] of tucatinib in combination with T-DM1 [Kadcyla; ado-trastuzumab emtansine] or T-DM1 alone in the second-line setting.

Erika P. Hamilton, MD, director of the Breast Cancer and Gynecologic Research Program and principal investigator at Sarah Cannon Research Institute, discusses the evolution of treatment in HER2-positive breast cancer.

Women with early-stage HER2-positive breast cancer respond well to current therapies, evidenced by the fact that half of women with metastatic HER2-positive disease have de novo metastatic disease. This doesn't mean that de novo disease is becoming more common, says Hamilton, but rather that the women who receive neoadjuvant therapy tend not to relapse.

As the paradigm continues to evolve, the field may see more trials with immunotherapy. Immunotherapy has shown success in triple-negative breast cancer, and smaller trials have combined immunotherapy with HER2-directed agents. There is no reason to think that the combination of an immunotherapy drug and a targeted agent couldn’t lead to synergistic benefit in the HER2-positive breast cancer space as well, concludes Hamilton.

Erika P. Hamilton, MD, discusses the evolution of treatment in HER2-positive breast cancer.

Sarah Cannon

Dr. Burris on Predictive Biomarkers for Chemoimmunotherapy in TNBC

Multidisciplinary Collaboration Needed to Provide Cohesive Care in Advanced NSCLC

Breast Cancer Chaired by Erika P. Hamilton, MD

Dr. Berdeja on Updated CARTITUDE-1 Results With JNJ-4258 in Multiple Myeloma

Dr. Graff on Future Research With Immunotherapy in Breast Cancer

Dr. Flinn on the Role of BTK Inhibitors in CLL

Dr. Burris and Dr. Graff Talk COVID-19 and Cancer Care, Telemedicine, and ASCO Initiatives

Tucatinib Approval Adds Impact to HER2+ Breast Cancer Paradigm

Tucatinib Approval Adds Impact to HER2+ Breast Cancer Paradigm

Dr. Hamilton on the Evolution of Treatment in HER2+ Breast Cancer