Shannon Connelly

When treating older patients with breast cancer cancer, one approach does not necessarily fit each patient, explained Arti Hurria, M.D.

“Treatment needs to be individualized for an older adult. A part of that process is knowing the data within oncology, but also the other part is knowing the data within geriatric oncology. That data being such that it can help you to individualize those treatment decisions. A key point is that to make a treatment decision with an older adult, you have to weigh not only what the benefits are, but also the potential risks of treatment,” said Hurria, who spoke on the topic during the 16th Annual International Congress on the Future of Breast Cancer.

Can you provide an overview of the treatment needs for older women with breast cancer?/strong>

What are some of the factors physicians should consider with older patients?

Is there a specific treatment or regimen that you prefer for older patients?

What are the main challenges when treating older patients?

Are there any ongoing trials in which you think the older population is well represented?

What do you envision the future of this space will look like?

, Hurria, director of the Cancer and Aging Research Program at City of Hope, discussed the unique challenges with treating elderly patients with breast cancer and the exciting opportunities she envisions for advancing care in this setting.

What I talked about was how you make a treatment decision for an older adult with breast cancer and the factors that you should consider in that treatment decision-making process. We talked about what the data is regarding treatment for older adults with breast cancer and then brought in some of the data from geriatrics in order to think about that decision-making process with that older adult.

The idea is that the aging process is very heterogeneous, so there is a real difference between chronological age and functional age as an individual gets older. Hence, there could be two 80-year-old individuals who are very different and who have very different functional statuses and other medical problems. All of that needs to be taken into account when you’re making that treatment decision. The idea is that if you can incorporate the principals of geriatrics into your oncologic care, you’ll be able to understand an individual’s functional age in comparison to their chronological age and utilize that when you’re making a treatment decision.

It completely depends upon many different factors, but one has to be how aggressive the tumor is. Also, when we’re devising a treatment regimen for an older adult, it’s important to think about the side effects. If an older adult has pre-existing neuropathy, we’re very careful about taxanes. If they have pre-existing cardiac disease, we think about caution with anthracycline-based regimens. It’s taking into account what their other medical problems are and then coming up with an individualized treatment plan for that patient. 

The main challenge that we face is that older adults have been underrepresented in clinical research, in particular, the FDA registration trials. The studies lead to the approval of drugs and inform the package insert of how to dose those drugs. There have been very few patients that are older adults included within those studies. The challenge that oncologists face is how do I then dose the drug in an older patient population when the drug has primarily been studied in younger adults.

There are now a number of studies that are focusing on the older patient population, across a whole range of research. There's something called the U13, which was a grant that was a collaboration between the Cancer and Aging Research Group, the NCI and the NIA. We had three conferences that laid out the research agenda for older adults and formed the platform for how this research should unroll within the next 10 years to help this patient population. One key part of that was the therapeutic studies and open studies that specifically focus on older adults, so we can understand how to dose these drugs and what are the side effects the patient might experience.

I think it’s going to be incredibly exciting. Right now, we’re in the midst of the baby boomers aging. By 2030, the largest growth in population is going to be people over the age of 80. These are the patients that we’re seeing, because cancer is a disease that is associated with aging. Any bit that we can move the needle in this space is going to have huge implications for our field and how we treat patients. With that in mind, it’s an incredibly exciting time for geriatric oncology and we welcome people to join us in doing this work so we can help this growing patient population.

The key point from my presentation was that treatment needs to be individualized for an older adult. A part of that process is knowing the data within oncology, but also the other part is knowing the data within geriatric oncology. That data being such that it can help you to individualize those treatment decisions. A key point is that to make a treatment decision with an older adult, you have to weigh not only what the benefits are, but also the potential risks of treatment.

Is there anything else you'd like to add?

To understand what those risks are, you can utilize a calculator that can calculate the risk of chemotherapy toxicity. You can go to the Cancer and Aging Research Group website and you can plug in 11 easy questions about your patient, and you can find out where they fall on the risk of side effects from cancer treatment, chemotherapy in particular. It will also tell you how you can intervene to try to decrease those risks. The biggest point is that chronological age does not equal functional age. Age tells us very little about an older adult, and if we can deepen the way we think about this patient population, we can individualize treatment decisions for them.

I’d like to add that it’s an absolutely wonderful patient population to take care of. You get to spend time with people’s moms, and their grandmothers, and their aunts, and those are all people that we love and we can learn so much from. I would advise anyone who is junior or just starting their career in this field of geriatric oncology, they have such a chance to make a difference, but not only that, the patient population is just incredible.

Articles

Individualized treatments are key for older patients with breast cancer, expert Arti Hurria, M.D. said.

Addressing the Needs of Older Patients With Breast Cancer

Imfinzi (durvalumab) — a PD-L1 inhibitor – gained Food and Drug Administration (FDA) approval last month to treat patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy, or for patients who have disease progression within a year of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The approval was based on the single-arm phase 1/2 Study 1108, which included 182 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression following platinum-containing chemotherapy.

In the study, the objective response rate per blinded independent central review was 17 percent. At the data cutoff, the median duration of response was not reached.

Please provide some background on Imfinzi leading up to its approval.

, Christophe Massard, M.D., Ph.D., medical oncologist, senior consultant of the Drug Development Department and Department of Medical Oncology, and chairman of the Early Drug Development Multidisciplinary Tumor Board, Gustave Roussy Institute, discussed the latest developments with Imfinzi in urothelial carcinoma.

Imfinzi is a selective, high-affinity, engineered human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. An ongoing, multicenter, phase 1/2 open-label study (NCT1693562) is evaluating the safety and antitumor activity of Imfinzi monotherapy in patients with advanced solid tumors, including locally advanced/metastatic urothelial carcinoma. An interim analysis of 61 patients with urothelial carcinoma in this study indicated that Imfinzi was well tolerated and associated with antitumor activity, particularly in patients with PD-L1—high disease (at least 25 percent of tumor cells or tumor-infiltrating immune cells express PD-L1), resulting in its breakthrough therapy designation by the FDA.

What adverse events were seen with Imfinzi on the trial?

What should patients and doctors look out for regarding serious or immune-related AEs?

In [the] phase 1/2 open label study of locally advanced/metastatic urothelial carcinoma patients [that led to the approval of Imfinzi, the treatment] was administered at 10 mg/kg every two weeks. Imfinzi showed favorable efficacy and an excellent safety profile in locally advanced/metastatic urothelial carcinoma patients.

Grade 3/4 treatment-related adverse events [AEs] occurred in less than 10 percent of patients. Grade 3/4 immune-mediated adverse events occurred in a minority of patients. Among patients with any-grade treatment-related AEs of special interest, patients received systemic steroids. 

Imfinzi, like other immune checkpoint blockers, generates atypical types of tumor responses—pseudoprogression, but also hyperprogression. Moreover, they have a specific toxicity profile that is challenging the historical oncologists’ practices, with the need to learn how to deal with the clinical management of immune-related AEs.

What is the impact of Imfinzi's FDA approval?

Is there potential for the agent to replace chemotherapy?

Most immune-related AEs remain mild in intensity but between 5 percent and 10 percent of patients treated with anti—PD-1 immune checkpoint blockers will develop severe, sometimes life-threatening grade 3/4 dysimmune toxicities. For example, it was decided at Gustave Roussy to set up a network of oncologists and organ specialists to manage patients with immune-related AEs. This program is led by Aurélien Marabelle, MD, PhD; Stéphane Champiat, M.D.; and Olivier Lambotte, M.D., Ph.D.

[The research] supports the manageable safety and tolerability of Imfinzi administered at 10 mg/kg every two weeks as monotherapy in patients with solid tumors and confirms its favorable clinical activity in previously treated patients with locally advanced/metastatic urothelial carcinoma for whom prognosis is poor. Imfinzi is clearly a new option for these patients.

Based on these findings, Imfinzi appears to be an attractive alternative to chemotherapy. Further studies, including DANUBE (

), are evaluating Imfinzi as a monotherapy and in combination with other agents (tremelimumab, AZD4547, Lynparza [olaparib], AZD1775, and vistusertib) in urothelial carcinoma.

Imfinzi (durvalumab) may change the treatment paradigm for some patients with urothelial carcinoma.

Expert Discusses Urothelial Carcinoma's Newest Agent

The field of prostate cancer has been transitioning with the identification of novel biomarkers. However, physicians are now facing a new challenge: which one is best appropriate for their patients? 

Leonard Gomella, M.D., recommends that healthcare providers familiarize themselves with how each biomarker should be used and then decide which one to use — a more individualized approach in clinical practice.

 Annual Interdisciplinary Prostate Cancer Congress, Gomella, professor and chair, Department of Urology, and director, Kimmel Cancer Center Network, Thomas Jefferson University, discusses the future of biomarkers in prostate cancer.

Can you give an overview of your talk on biomarkers in prostate cancer?

: Biomarkers in prostate cancer is a very rapidly evolving field. We’re seeing new markers for prostate cancer almost on a weekly or monthly basis. Right now, biomarkers for prostate cancer fall into two general categories: biomarkers that are used for the biopsy and initial diagnosis of prostate cancer, and biomarkers that are used after the diagnosis of prostate cancer.

In the first case, we primarily have new blood and urine tests that are out there to help us decide who may or may not have prostate cancer and who may or may not need a biopsy. In the latter case, after we make a diagnosis we have genomic tissue markers that allow us to be more clear on what the best treatment might be for a patient, either active surveillance or active therapies, such as radical prostatectomy or radiation therapy. And lastly, for patients who have had radical prostatectomy, we have biomarkers to help us decide if those with adverse pathology need more treatment, such as radiation.

Right now in prostate cancer, a lot of it revolves around what we call the somatic markers in the tumor to help us guide treatment. We have a whole different class of biomarkers now, both genomic and basic tests, such as the SelectMDx, 4Kscore test, the PHI (Prostate Health Index) test and other blood and urine tests, to help us with the decision for the initial biopsy.

With so many new biomarkers available, what are the challenges?

With all the biomarkers, the challenge is which is the best one. There are so many out there, and I think it’s up to the individual provider to start to work with one or two of the biomarkers and decide if they work well in his or her hands.

There are not a lot of comparative trials out there right now with the different biomarkers, either the standard blood and urine test, or the newer genomic assays on the tumor. We don’t have head-to-head comparisons, but the ones that are approved by the Food and Drug Administration (FDA), such as the PHI test, which is approved for the screening of the initial determination if someone needs a biopsy, doctors just have to start using them and decide which one works best.

Since there are not a lot of clinical trials ongoing in this area, what do you envision for the future of biomarkers in prostate cancer?

The future of biomarkers is going to be tough in the absence of clinical trials. There are a few centers that are doing some head-to-head comparisons. The FDA has the burden on them right now to approve these markers, and once they get approved, it’s going to be in your hands to decide which one works the best. Absent of these clinical trials, I think it’s going to be very challenging going forward as more biomarkers become available.

Let’s face it, we’ve had many biomarkers over the last 10 to 15 years that have come and gone because, although they got FDA approval, when they got out to the real world of patient care, the providers did not find that they helped in their decision making. Each new biomarker is going to have to stand on its own and I think once they get FDA approval, the marketplace is going to decide if it’s a good test, or ‘you know what, when I use this it doesn’t help me that much’ — it’s like flipping a coin. So again, each biomarker is going to have to stand on its own. The papers are all based on clinical trials and very defined populations, so once they get out into the day-to-day practice of urology and screening and diagnosis of prostate cancer, that’s where they will either live or die.

How can urologists best decide which biomarkers to use?

You have to first look at what the biomarker is approved for. Some biomarkers are approved for that initial yes or no decision making for biopsy. Other biomarkers are approved after the diagnosis is made for deciding whether you follow this patient with a less aggressive approach, such as active surveillance, or if they need some type of active treatment. The decision making has to be put in the context of what you’re doing with the individual patient.

The important thing is that any provider, whether it be a urologist, radiation oncologist, or medical oncologist, should be familiar with the different assays that are out there and understand that it’s not one-size-fits-all. They often have very narrow FDA labels for how they should be used.

Leonard Gomella, M.D., recommends that healthcare providers familiarize themselves with how each novel biomarker should be used and then decide which one to use for a more individualized approach in clinical practice.

Expert Discusses Biomarker Development in Prostate Cancer

Immunotherapy combination regimens may represent the future of urothelial carcinoma treatment, according to Evan Y. Yu, M.D., as it may be a novel approach to induce higher and more durable response rates in patients.

Additionally, while the success of immunotherapy has made a significant mark in the field, an unmet need still lies in the fact that these agents only provide a clinical benefit for approximately one out of every three patients, adds Yu, a professor in the Division of Oncology, Department of Medicine, University of Washington School of Medicine. Several ongoing clinical trials are examining immunotherapy agents in combination with other immune-based therapies, as well as with chemotherapy.

, Yu discussed the current treatment options for metastatic urothelial carcinoma, the unmet needs that still exist in this space and the possibilities for the future treatment landscape.

What are the current treatment options in metastatic urothelial carcinoma and what needs still have to be addressed with regard to treatment?

Yu: Right now, the first-line option for metastatic urothelial bladder cancer is still platinum-based chemotherapy — gemcitabine with cisplatin or gemcitabine with carboplatin. That may change in the near future as there are some frontline studies in patients who are cisplatin-ineligible and there are a couple agents that may get Food and Drug Administration (FDA) approval in that setting in the near future. But at this point in time, it’s still platinum-based chemotherapy for first-line.

Once you go into the second-line, most people are starting to use immuno-oncology (IO) agents. The FDA approved agents are the PD-L1 antibody, Tecentriq (atezolizumab), based on response rates and durability of response and the PD-1 antibody Opdivo (nivolumab), based on response rates and durability of response as well. Keytruda (pembrolizumab) is a PD-1 antibody that actually has the best level one evidence right now with survival benefit. However, Keytruda is still currently being evaluated by the FDA. We may see survival benefit in other studies in the near future, as Tecentriq has a randomized phase III trial that will probably read out reasonably soon.

That’s where we are in terms of FDA-approved agents. There are a lot of other exciting things being developed with fibroblast growth factor receptors (FGFR) antibodies, antiangiogenic agents and antibody drug conjugates.

There’s certainly an unmet need in the fact that there is no third-line approved therapy. There’s certainly an unmet need that the IO agents still only induce response rates in maybe 20 percent of patients and stable disease in up to another 15 percent. I generally tell patients that one out of three will have some sort of clinical benefit from an IO agent. How can we make it so that those patients who currently wouldn’t receive clinical benefit can respond in the future? Perhaps we need to do combination therapy. There certainly are combination trials that are ongoing that have promise for the future.

What impact has immunotherapy made in the field of urothelial carcinoma?

Immunotherapy has made a huge impact on the field. First off, we didn’t have any agents that induced an overall survival benefit and now we do. The first one was Keytruda. Second off, these agents are pretty low in toxicity. Other than the few patients who get immune-mediated side effects, they’re generally less toxic than cytotoxic chemotherapy. Thirdly, we see durable clinical benefit — people that respond or have stable disease resulting in long-term clinical benefit that may last one-to-two years or more. We just have not seen this with traditional chemotherapy. Last of all, we usually don’t see stable disease with chemotherapy. Either you respond or you progress, so stable disease is something new that has occurred with IO agents.

Where do you envision the treatment landscape for urothelial carcinoma will go in the next few years?

I think in the treatment landscape, IO agents will likely find their way as first-line therapy. First, they’ll get it in the first-line for patients who are cisplatin-ineligible, but there are trials underway that are comparing IO agents directly to chemotherapy. They may find themselves in first-line in combination with chemotherapy or as a single agent. However, we have to have some caution with single-agent IO therapy in the first-line, because there is a subset of patients that harbor rapidly progressive disease that could still be better served by chemotherapy since the response rates are initially higher with chemotherapy.

I would say that IO agents will likely move into the first-line eventually, but whether that’s as a single agent, or in combination with another immunotherapy agent or with chemotherapy, we will have to wait to see what pans out. Although, IO agents may not be right for everyone in the first-line, they will probably be administered for most patients in the first-line. As a result, I think it will lead to a shuffle to try to understand what’s best for second-line and third-line, but it leaves an opportunity to develop other drugs in other classes like I mentioned earlier; antiangiogenic agents, FGFR inhibitors and antibody drug conjugates are all very promising in this disease as well.

Finally, I think we will begin to better understand predictive biomarkers — who will respond and who won’t. At this point in time, I do not think the data is very compelling for prediction of response to therapy with PD-L1 immunohistochemistry, but hopefully in a few years we’ll have better markers to provide some predictive capability.

In an interview with CURE, Evan Y. Yu, M.D., discusses the current treatment options for metastatic urothelial carcinoma, the unmet needs that still exist in this space and the possibilities for the future treatment landscape.

Shannon Connelly

Addressing the Needs of Older Patients With Breast Cancer

Expert Discusses Urothelial Carcinoma's Newest Agent

Expert Discusses Biomarker Development in Prostate Cancer

The Future of Immunotherapy for Urothelial Carcinoma Treatment

Latest News