2022 Research Round Up: Multiple Myeloma, Breast Cancer, and Cancer in Adults 60 and Over

July 28, 2022
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In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in multiple myeloma, breast cancer, and cancer in adults 60 and over that was presented at the 2022 ASCO Annual Meeting, held June 3-7.



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In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in multiple myeloma, breast cancer, and cancer in adults 60 and over that was presented at the 2022 ASCO Annual Meeting, held June 3-7.

First, Dr. Sagar Lonial discusses a study on treatment for newly-diagnosed multiple myeloma in people under 65.  

Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the Cancer.Net Associate Editor for Myeloma.

View Dr. Lonial’s disclosures at Cancer.Net.

Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Winship Cancer Institute of Emory University in Atlanta, Georgia. And today I'm going to discuss one of the Plenary abstracts at ASCO 2022, which was the DETERMINATION study, again, presented at the ASCO Annual Meeting. For the sake of disclosure, I just want to make sure I list that I was an investigator on this study. I also have consulting relationships with Takeda, Celgene, BMS, Janssen, and other companies that have agents in the context of multiple myeloma.

So the reason I want to talk about this study today is I think it's a really important study that was designed over a decade ago to really ask the question, with a really powerful induction regimen that uses what we now call the RVd regimen, lenalidomide with bortezomib and dexamethasone, do you really still need to have high-dose therapy and autologous transplant as part of the treatment approach?

And so the trial was a very simple randomized trial that everybody received RVd induction. And then there was a randomization between early transplant and then going on to consolidation and continuous lenalidomide maintenance versus no transplant going on to consolidation and lenalidomide maintenance. So both arms actually received continuous lenalidomide maintenance, which is really one of the important endpoints of this study overall. And the reason I say that is there was a smaller study done in France a few years previous to this where patients only received 1 to 2 years of lenalidomide maintenance. And in that trial, clearly the use of transplant was better. And the remission duration for the group that received the transplant was about 48 months. So the question was, with continuous lenalidomide maintenance, can you make that longer?

So randomized trial, over 600 patients were randomized between these 2 arms. And the follow-up now is somewhere around 7 years in total. And what was demonstrated both in the ASCO Annual Meeting as well as in the paper that came out at the same time in the New England Journal of Medicine was that the remission duration was clearly longer in the group that had the transplant than the group that did not, even with both arms receiving continuous lenalidomide maintenance. And it was almost 66 months in the group that received the transplant, 21 months longer, almost 2 years longer than the group that did not receive the transplant. And so I think this is really important because what it says is that even in an era of really good induction therapy, transplant continues to offer significant benefit in terms of progression-free survival.

Now, the reason progression-free survival is so important in this study is that we know that no time is more sensitive for treatment of myeloma than that first time we treat the patient. And so prolonging that first remission is really important because the disease is at its most sensitive at that time point. Now, there were questions about overall survival. Should we see an overall survival benefit? And I'll tell you, A, this trial was never designed to measure an overall survival benefit. And, B, the median survival for myeloma patients is now between 10 and 15 years on average. And so with only 7 year follow-up, it seems to me unrealistic to expect this to have a survival benefit at this early time point. So rather than saying there's no difference in overall survival, I think it's a fair statement to say at the short follow-up we have, there is no difference in survival. But I actually don't think survival is the right endpoint for newly diagnosed myeloma trials in fit patients because we do have so many important treatments to discuss.

Now, there was also discussion about adverse events. Obviously, the quality of life during the transplant dropped a little bit. Not a big surprise. That lasted about 2 to 3 weeks, and then quickly, by 3 months out, returned back to baseline for almost every patient in the study. Additionally, there was a concern about second primary malignancies. If you look at this data, it's really no different than what we saw in the French study. There was a slightly higher risk of second primary malignancy, but we know that this is the case not only in myeloma, but in patients who receive alkylate-based therapy. And despite that, the progression-free survival was 2 years longer in the group that received the transplant than the group that did not.

So I think, in summary, this is really an important trial because there are many groups that are making the case that perhaps we don't need transplant in this modern era of myeloma therapy. And I think that it's important to recognize that what we're looking at are not short-term endpoints. We're not looking at early MRD (minimal residual disease) negativity. What we're looking at is really ultimate measurement of clinical benefit, which to me is prolonging that first remission as long as you can. And so this trial clearly demonstrates that for young, fit patients, transplant continues to offer significant benefit, almost 2 years of benefit with continuous lenalidomide maintenance. And while there's a push to say perhaps we can think about which patients may or may not need a transplant, honestly, as clinicians, we're not good enough to make that prediction. And what I think is really important is that we not lose sight of trying to prolong that first remission with the best tools that we have. And I think even in this modern era of 2022, high-dose therapy and autologous transplant continues to be one of those tools, and we want to use it to maximize the duration of that first remission. So thank you again for listening to this brief summary of the DETERMINATION trial presented at the 2022 ASCO Annual Meeting and published in the New England Journal of Medicine.

ASCO: Next, Dr. Norah Lynn Henry discusses new treatment advances for people with metastatic breast cancer, as well as 2 studies in early-stage breast cancer.

Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

View Dr. Henry’s disclosures at Cancer.Net.

Dr. Henry: Hi. I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2022 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both metastatic and early-stage breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We typically treat those cancers first with antiestrogen treatments, which block estrogen or lower estrogen levels. Other breast cancers are called “HER2 positive.” These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or very much HER2. These are called triple-negative breast cancer and are also often aggressive cancers.

One of the biggest stories from the ASCO Annual Meeting was the results of the DESTINY-Breast04 trial. In this trial, researchers studied a type of medication called trastuzumab deruxtecan, which is also called Enhertu. This drug is a combination of the anti-HER2 antibody, trastuzumab, plus a chemotherapy drug, and the antibody targets the drug to the cancer sort of like a guided missile. Trastuzumab deruxtecan is currently routinely used to treat patients with metastatic HER2-positive breast cancer. Now, the interesting thing is there was already data from studies that suggested that this drug might also work against breast cancers that have some HER2 receptors on the surface of their cells, but not so many that they meet the true definition of being HER2 positive.

For the DESTINY-04 study, patients' tumors had to have either 1+ or 2+ HER2, which some people called “HER2 low,” and could be either estrogen receptor positive or negative. Two thirds of the patients were treated with trastuzumab deruxtecan, and the other one-third were treated with 1 of 4 different standard chemo regimens that their physician thought was the best treatment option for them. Treatment with trastuzumab deruxtecan was shown to lengthen the time people were able to remain on treatment. Importantly, it was also shown to increase the overall survival of patients compared to standard chemotherapy by more than 6 months for patients with estrogen receptor-positive cancer and by more than 10 months for patients with estrogen receptor-negative cancer. Since this is a drug that we currently use to treat patients with other types of cancer, we actually know a lot about its side effects. One key toxicity is it can cause a very severe inflammation of the lungs in a very small subset of patients. So this is something that we have to watch for very carefully. Otherwise, it is a relatively well-tolerated drug, especially compared to standard chemotherapy. The main side effects are nausea and fatigue.

Another clinical trial presented at ASCO called TROPiCS-02 also studied a drug that is currently used to treat a different type of breast cancer. In this case, the drug is sacituzumab govitecan, also called Trodelvy. It is also a combination of an antibody that is targeted against cancer cells plus a chemotherapy drug. Sacituzumab govitecan is currently approved to treat metastatic triple-negative breast cancer.

In the TROPiCS-02 trial, however, it was tested to see how effective it is for treating hormone receptor-positive, HER2-negative metastatic breast cancer. All of the patients enrolled in this trial had already been treated with antihormone therapy medications as well as at least 2 chemotherapy regimens. Half of the patients were randomized to treatment with sacituzumab govitecan, and the other half were treated with 1 of 4 standard chemotherapy drugs that their physician thought was the best for them. Those patients who were treated with sacituzumab govitecan had a longer time on average that the treatment worked compared to those who received standard chemo. They also had improved quality of life based on responses that the participants themselves provided on questionnaires. Although the overall benefit was rather modest, this drug may represent a new treatment option for patients with hormone receptor-positive, HER2-negative metastatic breast cancer, although at this time it isn't yet approved for treatment of this type of breast cancer. Both of these are examples of being able to take drugs that have been shown to treat 1 type of cancer and potentially expand it so that they can be used to benefit more patients with breast cancer. These drugs are also being tested to see if they are beneficial for treating early-stage breast cancer. So we await more hopefully very exciting results in the future.

To switch gears a little bit, I'll now talk about another study I found interesting. This one is in the setting of early-stage breast cancer. So typically, radiation therapy is recommended after lumpectomy since it reduces the likelihood of cancer returning in the breast. However, questions have arisen about how much benefit radiation is actually providing for some patients whose risk of having cancer return in the breast is really low to start with. Therefore, these patients may be at risk of the side effects of radiation as well as other risks, such as financial problems, without actually getting much benefit from the treatment.

Therefore, this trial, called LUMINA, evaluated whether radiation therapy was beneficial after lumpectomy for patients who have small, low-risk breast cancers and no lymph node involvement. The trial included 500 women who were at least 55 years of age with invasive ductal cancers that were no more than 2 centimeters in size. They had to be estrogen receptor-positive, HER2-negative, either grade 1 or 2, and Ki-67 low. Everyone had to be planning to take antihormone therapy for at least 5 years. During the 5-year follow-up period, a total of 10 patients out of 500, about 2.3% of all patients, had their cancer return in the breast. The researchers therefore concluded that for patients with this type of very low-risk breast cancer, it is reasonable to omit radiation therapy and just take endocrine therapy. Similar results have previously been shown for patients over the age of 70 with small lymph node-negative low-risk cancers, but this trial expands that option to patients who are as young as 55.

Finally, I will touch briefly on the updated results from the ABCSG-18 clinical trial. So this trial enrolled postmenopausal women with early-stage estrogen receptor-positive breast cancer who are being treated with aromatase inhibitor therapy. Aromatase inhibitors are known to cause reductions in bone density. This trial therefore evaluated a medication called denosumab, also called Prolia, which is used to treat osteoporosis. Participants were randomized to treatment every 6 months with either denosumab or a placebo. They found that the patients who were treated with denosumab were half as likely to have a bone fracture. Importantly, patients treated with denosumab also had an improvement in bone density despite taking the aromatase inhibitor medicine, whereas those who received placebo had a decrease in their bone density over time.

The other very interesting thing from this study is that patients who received treatment with denosumab were less likely to have their breast cancer return or to develop a new cancer during the 8-year follow-up period. So it's actually already recommended that postmenopausal patients with all types of early-stage breast cancer consider treatment with a different type of bone strengthening medicine called a bisphosphonate as part of their breast cancer treatment. The goal is to further reduce their risk of cancer returning. These new results will now lead experts to debate whether to also include denosumab as a potential additional breast cancer treatment option, not just to help protect people's bone density.

There were a lot of other research findings presented that were related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, and we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2022 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry.

Finally, Dr. Shakira Grant discusses 3 studies that looked at cancer in people 60 or older. This field is also known as geriatric oncology.

Dr. Grant is an Assistant Professor in the Divisions of Hematology and Geriatric Medicine at the University of North Carolina at Chapel Hill and a board-certified Geriatric Hematologist/Oncologist.

View Dr. Grant’s disclosures at Cancer.Net.

Dr. Grant: Hi, everyone. I am Dr. Shakira Grant. And I'm an assistant professor at the University of North Carolina at Chapel Hill. I'm also a clinician scientist with a focus on social disparities and how they influence the health and aging of older adults with cancer, primarily multiple myeloma. And for today's talk, I have no relevant conflicts of interest to disclose.

It's such a pleasure to be able to talk today about the ASCO 2022 geriatric oncology and presenting key studies, which I believe were really practice-changing or really set up the foundation for informing future research directions. And to start us off, I wanted to start us with abstract 12012 by Dr. Mackenzie Fowler. And this was presented based on the University of Alabama at Birmingham's actual research group. And the title of their presentation was “Rural-Urban Disparities in Geriatric Assessment Impairments and Mortality Among Older Adults with Cancer.” And this was the result of a large registry study, predominantly patients with gastrointestinal cancer-- so cancers such as liver cancer, colon cancer. And what the authors really wanted to do here was to explore if whether or not living in a rural location, for example, is associated with having an impairment based on what people report in their ability to function at home, their quality of life. And they also wanted to see whether or not where you live, meaning a rural location, whether that can be associated with how long you are expected to live or your overall survival.

So this was really a study that took patients who were truly older. There were patients who were above the age of 60. As I mentioned, these were patients predominantly with cancers of the liver, the colon, and the pancreas. And patients completed a baseline, what we call a geriatric assessment, to try to assess their overall or global health. And on these assessments, patients are asked questions about how they would rate their physical function and their quality of life. And what the authors found here is that in general, when patients lived in rural areas, this was associated with patients self-reporting more functional deficits, meaning that they reported that they had impairments in the ability to function at home from a physical perspective. They also had impairments in quality of life—so how you rate your general life and how you're doing from a day-to-day basis. And this was impaired if you lived in a rural residence. And then, importantly, this study also showed that living in a rural location—and, again, this study was centered in Alabama—that that was also associated with a reduced overall survival, meaning that people were found in rural areas to live a shorter life with these cancers compared to those who live in non-rural places or, as we call it, urban.

And I think why I chose this particular study is because it's one of the first studies using a large data set of almost 1,000 patients that they have enrolled and really looking at the idea of the physical environment, so where a person lives, and how that really interacts with everything else to influence the health of an individual. And this study, I believe, really lays the foundation for an area of work in geriatric oncology where we are moving away from just thinking about the older adult, but we're also thinking about the older adult and the other identities. So we're really considering the sociocultural influence. So we think about race. We think about socioeconomic status, income. But now, we're also including the physical environment. And that is where people are living and spending the majority of their time. And that is in this study classified as rural-urban residency. So for this study, overall, I would say that this is really moving the field forward in a direction where we're moving away from just looking at just older adults, but we're thinking about older adults and all of the other stressors that they face, especially when they live in the community and how that impacts their health.

The next study that I wanted to highlight was a study that was performed by Dr. Heidi Klepin at Atrium Health, Wake Forest Baptist. And this was a study that looked at evaluating the association between an electronic health record-embedded frailty measure and survival among patients with cancer. Again, this was an older adult population. It was just over 500 patients involved, and patients were over the age of 65. They had a new diagnosis of the most common cancers, which are lung cancer, colon cancer, and breast cancer. And the good thing about this particular study is that it sought to use data that is readily captured in the electronic health record to characterize a patient as fit, prefrail, and frail. So why is that important for the geriatric oncology community and even beyond is when we're dealing with older adults, we're always thinking about ways in which we can actually characterize their fitness and their ability to hence tolerate their therapies, being chemotherapy, and how likely they are to die if they're having these functional impairments.

And so importantly, what this study showed was that in their sample, they found that up to 17% of people were characterized as frail using this index. And the significance of this finding is that when they looked at how long people were likely to live with these cancers, breaking it down according to if you were fit, prefrail, or frail, those who were frail had the shortest overall survival. So it means the time from which they were diagnosed until they die was much shorter than any of the other categories. And that equated to a difference between those who were fit and those who were prefrail of 10 months for those who were frail for overall survival and more than 54 months for those who were actually considered to be fit. So this is really, really important because what we are seeing is that if you are really fit, you are living on average with these cancers—the overall survival, at least for their institution, was more than 54 months. But then as you move across that spectrum of fitness, we're actually seeing that your survival decreases significantly.

And so why is this important? So this is important because it's one of the first studies that is actually looking to operationalize the frailty measure for us to be able to potentially use and adapt into other health systems using data that we already collect. So it's no longer burdensome on patients to try to fill out additional forms or for other staff to be involved and collect this data. And this data is showing us that there is an association with this particular frailty index and the ability to predict overall survival-- so, again, a critical study in the geriatric oncology population looking at patients with the 3 most common types of cancer, which are lung cancer, colon cancer, and breast cancer, and really showing us that there is a way potentially to operationalize how we characterize the fitness level of an older adult and then using that data not just to say, "Yes, this person is frail," but for us in real-time to see results where we can see that there is a significant difference in terms of overall survival.

Importantly, this is going to be a study where we continue to watch closely the developments over the next few years, especially as the authors and the research team note that their next steps involve looking at how to study how these frailty measures, or the frailty scores that people get when they come in and they're at baseline, how this changes throughout the course of treatment. And that has a lot of implications because now, we have the potential to start thinking about using a frailty-adapted approach to caring for older adults with cancer. What that means is when you're getting your treatment and we are following these scores, as we see things changing, this may be an indicator to us that, "Hey, we need to make some modifications in response to these frailty measures to make sure that our older adult population is able to tolerate their chemotherapies and have maximum benefit while also enjoying a good quality of life."

So finally, I want to highlight this third study. And this was a study that was presented by Dr. Etienne Brain. And. Dr. Etienne Brain was also this year's B.J. Kennedy Award recipient. And each year ASCO recognizes the B.J. Kennedy Award recipient as an outstanding investigator who has made significant contributions in the area of research and clinical care of older adults with cancer. In this particular study, Dr. Etienne presented on behalf of his team the final results from a study that was looking at using endocrine therapy with or without chemotherapy for older adult women, so characterized as those who were over the age of 70, with a diagnosis of estrogen receptor-positive, HER2-negative breast cancer. And the importance for this study is that the question they sought to examine was whether or not patients who are in this age range still derive a benefit from receiving chemotherapy in addition to endocrine therapy.

And what this study really showed is that there was no survival difference. Meaning when they looked at the data for 4 years, those who got chemotherapy plus endocrine therapy lived just as long as those who also just got endocrine therapy alone. And why this is important is because when you think about giving chemotherapy to an older adult population, as oncologists, we are always weighing the risks and the benefits associated with treatment. So we're always thinking about how tolerable is this drug likely to be? We want to minimize side effects because, at the end of the day, our goal is to treat the cancer, but we also want to focus in on the outcomes that matter most to the older adult population. And in general, these are things like maintaining your mobility, maintaining your mentation, maintaining good quality of life. And so we really want to make sure that we're balancing those risks. And this is why this particular study showing that with chemotherapy or without chemotherapy added to endocrine therapy, there seems to be no survival difference. This could be a way in which we move the field forward in thinking about a select group of patients with breast cancer and whether or not those patients truly need that extra toxicity or burden associated with using chemotherapy or whether endocrine therapy is enough.

So with that, I will say across these 3 studies, even though they study different things-- we saw 1 study that looked at the intersectionality between older adults in terms of their chronological age but now starting to examine the influence of physical or social context and how that influences the health and outcomes for individuals with primarily gastrointestinal cancer. We also looked at the development of an electronic frailty index in patients with 3 most common solid tumors - lung cancer, colon, and breast cancer - and found that by using this frailty index collecting readily available data, that there was an association with predicting overall survival. And we saw that those who were characterized as frail had one of the shortest overall survivals. And then finally, in this study, looking at endocrine therapy alone versus chemotherapy and endocrine therapy, we saw that there was no survival difference again in an older adult population. And so what we are seeing here is a theme emerging as the importance of comprehensive evaluations of older adults and the importance also of these measures, when integrated across the research continuum, that they are useful in terms of predictive prognostic abilities and really lay the foundation for future research. So with that, I want to thank you for your time and thank you for listening.

ASCO: Thank you, Dr. Grant.

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