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Answers straight from the experts on the latest news and topics in oncology

Monday, January 11, 2021

With Lori J. Pierce, MD, President of the American Society of Clinical Oncology

By Sarah DiGiulio​

Late last year, the American Society of Clinical Oncology (ASCO) launched an educational series of podcasts, videos, and blog posts focused on the role of social determinants of health in cancer care and cancer outcomes. The series is available online for free for ASCO members, other members of the oncology community, and the general public. But the initiative was developed specifically for oncology trainees and early career oncologists.

“As cancer care providers, we have a responsibility to not just study how biology affects disease progression, but also understand how social determinants affect the lives and cancer outcomes of our patients," ASCO President Lori J. Pierce, MD, said in a statement. “Our work to develop and deliver cancer breakthroughs is all for naught if our patients don't have transportation to access treatment, money to pay for it, or trust in the level of care they will receive."

The video series is available on YouTube and the podcast version of the series is available on the ASCO eLearning website. New episodes will be added to both channels throughout 2021.

In an interview with Oncology Times, Pierce shared her thoughts about the series and why the topics covered are important for young and more experienced cancer care providers.

1. What can members of the oncology community expect to learn from this series?

“This series will be about social determinants of health and modifiable risk factors for cancer. Social determinants of health are important because they are significant factors behind various health outcomes. The World Health Organization defines social determinants of health as conditions in which people are born, grow, live, work, and age. As such, the term includes factors such as economic status, one's physical environment, education, food, and the health care ecosystem.

“One of the episodes in this series will be dedicated to how to take a social determinants of health history because it is important that, as providers, we understand why patients are sometimes unable to adhere to the treatments proposed, understand the difficulties they face in receiving care, and what we can do to eliminate some of these barriers. If we have not asked the right questions and elicited the appropriate responses in our usual history taking, we are unaware as to what the underlying barriers to care patients are truly experiencing.

“For example, lack of transportation or other financial considerations could result in a patient's inability to come for treatment. Arranging means for transportation could remove that barrier to care.

“Another example is that we want patients to be able to exercise to improve their overall health and perhaps improve their ability to tolerate cancer therapies. But if patients live in environments where they cannot go outside safely to exercise, we need to help them think through alternate ways to safely exercise inside. As for food choices, some of our patients may live in communities where it is difficult to access certain types of healthy foods. Finding ways to help our patients secure healthy meals and suggestions of healthy food alternatives that may be accessible could meaningfully modify health outcomes."

2. Who is the intended audience for this series?

“While we hope the series will be accessed by a large cross section of ASCO members, the target audience is fellows and early career physicians who are our future leaders in oncology and our future leaders in ASCO.

“We have a task force for this initiative consisting of oncology fellows and early career physicians. With their input and the input of the chairs of ASCO's Prevention Committee and the Health Equity Committee, we are collectively deciding the topics to be discussed and the ASCO members to engage in the various episodes. We are also hoping to incorporate this series into training programs to disseminate its content broadly. We are quite excited about this initiative and hope it extends our collective knowledge so we can better deliver high-quality care to all of our patients."

3. Currently the series is optional. What's your pitch to practicing oncologists or trainees as to why they should listen in?

“These factors very much impact the cancer outcomes of our patients. We have so many wonderful therapies to offer patients; but if patients cannot access them, our therapies are all for naught. If certain segments of our patient population can't access recommended therapies, we cannot provide equitable care to all."

Tuesday, December 22, 2020

With Andrew Evens, DO, MSc, of Rutgers Cancer Institute of New Jersey​

By Sarah DiGiulio

Though Hodgkin lymphoma is highly curable, its late effects can be costly financially and in terms of survivor quality of life. Cost-per-death analyses show it has the second-highest cost per death or lost-productivity cost (Int J Cancer 2015;136:E136-E145). And productivity analyses of cancer mortality have shown Hodgkin lymphoma to be the second most costly cancer in terms of lost lifetime earnings (J Natl Cancer Inst 2008;24:1763-1770).

The high rates of late effects are due to increased incidence of cardiovascular disease, second malignant neoplasms, and other prominent treatment-induced morbidities that may result in excess morbidity and early mortality, explained Andrew Evens, DO, MSc, Director of the Lymphoma Program, all at Rutgers Cancer Institute of New Jersey. In a recent editorial in the Journal of Clinical Oncology, Evens and colleagues comment on a recent dataset that reveals a large number of patients experience side effects quite soon after treatment (J Clin Oncol 2020; doi: 10.1200/JCO.20.02668, 2020; doi: 10.1200/JCO.20.00264).

“There are many previous reports delineating the increased rate of late effects occurring more than 20-30 years after therapy," Evens noted. “However, [this recent] analysis shows that increases in treatment-related morbidity and early mortality occur within the first decade after therapy (and as early as 1 year) with modern, frontline therapy."

While this new data is important, Evens and his coauthors note that real-world data consisting of individual patient data must also be carefully culled and harmonized and put into flexible decision models so clinicians can learn from and translate that learned knowledge into practice for short-term and long-term outcomes for individual Hodgkin lymphoma patients. The benefits and risks of different therapies depend on several characteristics, including patient age, sex, and disease stage, among other factors.

Evens is a co-principal investigator for the HoLISTIC [Hodgkin Lymphoma International Study for Individual Care] consortium and is doing that work. He shared his thoughts with Oncology Times about the endeavor.

1. What interventions and might lessen these crippling late effects of Hodgkin lymphoma?

“A critical consideration is to continue studies to delineate more individualized therapy for patients with Hodgkin lymphoma, [including] efforts to harmonize large amounts of individual patient-level data on efficacy and toxicity (acute, post-acute, and late) across varying treatment platforms that are applicable to diverse settings across the world to aid in decision-making. In addition, continued efforts are needed to examine the de-escalation of therapy for low-risk patients with Hodgkin lymphoma via response-adapted strategies and/or integration of targeted therapeutic agents.

“Efforts are underway to harmonize large amounts of individual patient-level data for patients with Hodgkin lymphoma treated in recent international clinical trials and from prominent cancer registries and survivorship cohorts. More breakthroughs are needed to aid with prognostication and prediction of therapy beyond early/interim PET response adaption, such as ctDNA and other technologies.

“The ongoing North American clinical trial, S1826 (NCT03907488), for advanced-stage classic Hodgkin lymphoma is examining a host of correlative scientific studies, as well as health outcomes, cost effectiveness, and health-related quality-of-life analyses."

2. Can you talk more about the work of the HoLISTIC consortium?

“[HoLISTIC researchers] are harmonizing detailed individual patient-level data from 15 large Hodgkin lymphoma clinical trials in the modern era of newly diagnosed Hodgkin lymphoma patients, as well as individual patient-level data from six large Hodgkin lymphoma registries—the latter considered more 'real-world data' and enriched with longer follow-up and crucial information on post-acute toxicities. Applying established data science methods, we have created a common data model with a data dictionary across all sources that will result in a detailed and fully annotated database of [approximately] 20,000 Hodgkin lymphoma patients.

“We will use predictive modeling and multi-state modeling that incorporates interim/early PET and tumor biology with varying treatment platforms to create simulation/decision modes. They will be designed to incorporate future prospective data as new/novel treatment that will delineate acute, post-acute, and late effects and outcomes for individual Hodgkin lymphoma patients. Importantly, this robust database has been designed to incorporate new studies and data and longer-term outcomes as they become available."

3. What is the ultimate message of this work?

“Providers should know that significant treatment-related toxicities and early mortality, such as heart disease, infections, lung disease, and second cancers, are seen with modern therapy and occur the first decade after treatment (and as early as 1 year after diagnosis). Currently, this should highlight the importance of survivorship for Hodgkin lymphoma patients, and the development of survivorship plans should be a critical part of each patient's post-therapy care within 1-2 years.

“Additionally, clinical studies leveraging more targeted therapeutics for Hodgkin lymphoma patients are ongoing and predictive modeling and data simulation efforts such as HoLISTIC and the pediatric cancer data commons are underway to harmonize data for Hodgkin lymphoma of all ages and geographies to aid with data standardization and create predictive tools that delineate short- and long-term outcomes across varying therapeutic strategies for individual Hodgkin lymphoma patients."

Tuesday, December 8, 2020

With Evandro De Azambuja, MD, PHD, & Noam Falbel Pondé, MD, of the Jules Bordet Institute

By Sarah DiGiulio

Older patients with breast cancer differ from younger patients with breast cancer in many ways. Comorbidities are different. Regular medication use is different. Levels of independent living and functioning are different. And personal priorities are different.

Yet, sufficient evidence that explains how to tailor treatment for these patients that takes all of these differences into account is lacking, according to an editorial recently published online ahead of print in the Journal of Clinical Oncology (2020; https://doi.org/10.1200/JCO.20.02329).

“Studies that focus on this underserved population, therefore, are of high scientific, public health, and social value," the authors note in the editorial.

Evandro de Azambuja, MD, PhD, Head of the Medical Support Team at the Jules Bordet Institute in Brussels; Noam Falbel Pondé, MD, a medical oncologist and medical research fellow also at the Jules Bordet Institute; and the other co-authors specifically comment on the results of the RESPECT trial that compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy for older adults with breast cancer, which were also published online ahead of print in JCO (2020; https://doi.org/10.1200/JCO.20.00184).

In an interview with Oncology Times, they shared their thoughts about that data and why further research in this area is important.

1.       One of the points you make in the editorial is that older adults have been historically understudied in clinical trials for breast cancer. Can you elaborate on what factors have led to these patients being excluded?

PONDÉ: “Changing demographics are key here. Most of human societies today are aging, a process called demographic transition. Life expectancy is increasing. This is true in both developed and developing countries and has many causes.

“Older persons being a larger proportion of the population and, additionally, having a higher risk of having cancer means for oncologists a larger number of older patients seen at the clinic every day—which alone justifies the need for more research efforts in the area of geriatric oncology.

“As to why this population has been historically underrepresented in clinical trials, a number of explanations are available and ultimately I think all of them are correct. First, due to safety concerns, many trials exclude older patients. In the past, age-based exclusion criteria were a reality. But though these are not common today, other exclusion criteria can keep older patients out—for example, those that focus on serious comorbidities or altered laboratory test results—which will of course be more frequent in older patients. Another problem is that physicians themselves overlook older patients for trial participation due to safety concerns."

 

2.       Your editorial mentions results from the RESPECT trial. What was noteworthy about that research?

AZAMBUJA: “Older patients are a highly heterogeneous population. As we can see in daily life, a 75-year-old woman can be completely independent, live on her own, work, and be a caregiver for other family members. On the other hand, she can be the one in need of care due to a stroke, for instance. It means some older women don't tolerate chemotherapy well—risking loss of functionality, neutropenia, possibly the need to be admitted to the hospital for a chemotherapy-related complication.

“The results of RESPECT suggest that for small, node-negative, HER2-positive breast cancer, the loss in efficacy due to suppressing chemotherapy is very minimal—and therefore we can give to some women trastuzumab alone safely—protecting them both from disease recurrence and chemotherapy toxicity."

 

3.        So, how do we shift the paradigm and improve treatment and care for these older patients?

PONDÉ: “Better care for older patients is a huge challenge for our health care systems. In oncology, two key changes to improve care for this populations are [first] to create/expand geriatric oncology services so that eventually all older patients can benefit from being cared for within such a setting. Second, more trials focused on older patients are critical, and some research groups like the European Organization for Research and Treatment of Cancer (EORTC) are to be commended for focusing on this and producing highly valuable data.

“It is also important to add that the way toxicity is evaluated currently in clinical trials is suboptimal—even more so for older patients. Ideally, older patients in clinical trials would be followed by trained geriatricians to evaluate the long-term impact of adverse events, particularly those who lead to hospitalization or to increase mortality due to complications." AZAMBUJA: “Most patients with early HER2-positive disease have exceptionally good outcomes today, largely due to anti-HER2 antibodies. Trials such as RESPECT point the way in which our field needs to advance for many patients—de-escalation of chemotherapy. This is true for all patients, particularly older ones."


Wednesday, November 25, 2020

With Crystal Aguh, MD, Assistant Professor of Dermatology and Director of the Ethnic Skin Program at Johns Hopkins School of Medicine​

By Sarah DiGiulio

Scalp cooling treatment can help prevent one of the many unpleasant side effects of chemotherapy treatment: hair loss.

“We know that hair loss has a major impact on quality of life," said Crystal Aguh, MD, Assistant Professor of Dermatology and Director of the Ethnic Skin Program at Johns Hopkins School of Medicine. “Chemotherapy-induced hair loss is often considered the most distressing side effect of chemotherapy treatments, having devastating impacts on quality of life with nearly 10 percent of patients declining chemotherapy altogether."

But scalp cooling treatment isn't effective for everyone. Aguh recently coauthored a correspondence that was published online in the Journal of Clinical Oncology about why scalp cooling treatment has different results for women with different hair types (2020; doi: 10.1200/JCO.20.02130). The article explains that women with black curly or kinky hair may require further considerations in the instructions for preparing hair before scalp cooling treatment. And the difference in thickness and structure of their hair may bear on the effectiveness of the scalp cooling treatment.

“Although straight hair and curly hair have identical chemical properties, the difference in physical properties such as shape, texture, and density may necessitate further considerations in the instructions for preparing hair before using scalp cooling devices," the article notes.

In an email interview, Aguh explained the predicament of one of her patients prior to scalp cooling treatment. For that patient, the current guidelines and instructions were not applicable for her type of hair.

“She was concerned that the instructions to wet her hair for improved conduction would cause it to become very curly and bulky—and prevent the cooling cap from fitting tightly. Additionally, the detangling hairbrush provided in the kit historically has led to hair breakage and she was anxious about using it, but wanted to maximize her likelihood of success," noted Aguh.

She had a discussion with the patient about different hair styling options—like braiding or chemically straightening it—to maximize effectiveness of the scalp cooling treatment. But evidence to guide that conversation was very limited.

“There was virtually nothing in the literature that could help guide our recommendations," Aguh said. Here's what she said about the problem and the research that needs to be done.

1. Why and how might the effectiveness of scalp cooling treatment be affected by someone's hair type, texture, and usual care routine?

“To ensure that the scalp is cooled to the requisite goal temperature, proper cap fitting is critical. Although differences in hair texture and shape among different ethnic groups may appear trivial, the effectiveness of scalp cooling is affected by factors determined by the hair type.

“Computer modeling of scalp cooling has correlated hair thickness with decreased effectiveness of scalp cooling. This is a troublesome characteristic for Black women, whose naturally curly hair increases fullness and makes cap wearing difficult. Unfortunately, the majority of data assessing efficacy of scalp cooling therapy reflects its use on white patients."

2. So what do you think should be done to address this problem and make sure that effectiveness of scalp cooling treatment is effective for everyone?

“Limited data has suggested that scalp cooling is less-effective in people of African descent for unknown reasons. Research is needed to see if differing hairstyles are more or less likely to lead to treatment success in Black women. What we offer in the article are some hairstyling suggestions for Black women that can be used until better data is available.

“But studies are needed that directly address this question of efficacy in Black patients compared to women of other racial/ethnic groups undergoing scalp cooling or the impact on different hair styling practices on results."

3. What's the takeaway message that practicing oncologists and cancer care providers—as well as other researchers—should know about this problem?

“Reducing barriers for successful scalp cooling treatment in Black women has the potential to increase the number of women choosing to undergo lifesaving chemotherapeutic treatment. This underscores the need for a greater understanding of hair types and styling practices among different racial groups.

“It's clear we need better physician understanding of the unique properties of Black kinky/curly hair, its properties, and styling differences [compared with] straight hair. Though straight hair and curly hair have identical chemical properties, the difference in physical properties such as shape, texture, and density may necessitate further considerations in preparation instructions for the use of scalp cooling devices."

Friday, November 13, 2020

With Michael Schweizer, MD, Assistant Professor in the Division of Medical Oncology at University of Washington​

By Sarah DiGiulio

The FDA has recently approved two poly (ADP-ribose) polymerase (PARP) inhibitors, rucaparib and olaparib, for men with metastatic castration-resistant prostate cancer (mCRPC) and mutations in homologous recombination repair genes. That should be good news for patients with this type of cancer and for proponents of precision medicine.

But in a new “Comments and Controversies" article in the Journal of Clinical Oncology, Michael Schweizer, MD, Assistant Professor in the Division of Medical Oncology at University of Washington in Seattle, poses words of caution (2020; doi: 10.1200/JCO.20.01755).

Both rucaparib and olaparib were recently approved by the FDA for treatment for patients with prostate cancer, but the former's approval is restrictive to only BRCA1- and BRCA2-mutated prostate cancer and the latter's approval is permissive of a larger number of genes directly and indirectly involved in homologous recombination repair. The approval for olaparib includes several genes that, to date, have not individually been shown to predict for response to PARP inhibition, Schweizer noted in the JCO article.

“We were surprised at the stark differences in their respective labels," Schweizer told Oncology Times. “I don't think revoking the approval is necessary; physicians just need to be judicious in how they use olaparib."

Here's what else he said about the approvals and how physicians can be more judicious in their use of the new drugs.

1. One of the issues you bring up in the editorial is that the evidence supporting the efficacy of both drugs is different. Can you explain the key differences between the evidence that led to the approval of both drugs?

“Rucaparib received accelerated approval on the basis of the non-randomized TRITON2 study. In this study, they observed low response rates in men with mutations in genes other than BRCA1/2. As such, they focused their efforts on developing rucaparib for the subgroup with BRCA1/2 mutations only.

“Olaparib was approved on the basis of the randomized Phase III PROfound study. This trial allowed patients with a long list of homologous recombination gene mutations to enroll. The primary analysis focused on those with BRCA1/2 or ATM mutations (cohort A). A second cohort (cohort B) allowed patients with mutations in other homologous recombination genes. Secondary endpoints evaluated the outcomes in the combined Cohort A and B group. Because primary and secondary endpoints were met, the FDA granted approval across almost every gene that was included in the study eligibility. PPP2R2A was not included in the label because there was a trend toward worse outcomes with olaparib treatment in these patients."

2. So what do you find problematic about the data from the olaparib study?

“PROfound was a positive study and the statistical plan laid out in the protocol was followed, so I don't think you can claim the results were misinterpreted.

“However, when you look at the data, it is fairly clear that the observed benefits were primarily driven by the group with BRCA mutations. If you focus on the patients with non-BRCA mutations, it's hard to conclude that olaparib is more effective than the control. It is likely that olaparib works well in some patients with non-BRCA mutations (such as PALB2), but it is also likely that it does not work for every gene included in its FDA label (such as CDK12).

“I generally favor broad indications since this gives physicians more latitude to use their judgment in treating patients. We just wanted to make sure that physicians understand that the benefit of olaparib in those without a BRCA mutation has not been clearly demonstrated. My concern is that drugs that have clearly demonstrated efficacy (such as docetaxel) may get overlooked in favor of olaparib, which could lead to poor patient outcomes in some cases.

“More studies are needed to understand which mutations are predictive of response to PARP inhibitors. Olaparib's broad label will likely be a barrier to completing these studies since many patients will receive this as standard of care and not be enrolled to studies designed to determine the efficacy of PARP inhibitors in non-BRCA mutated subgroups."

3. What's the bottom-line message practicing oncologists and cancer care providers should know about these drugs?

“For patients with a non-BRCA homologous recombination mutation, I would advocate that they participate in a clinical trial. If this isn't an option, it's important to critically evaluate the data supporting the use of PARP inhibitors for a given mutation. In some cases, other drugs may be a better choice. Of course, if there are no other options for an individual and olaparib is still on the table, I would certainly consider using it."