Conference Coverage: NCCN Policy Updates

Future of Biosimilars in Cancer Care Will Require a Balancing Act, Lyman Says

Acceptance of biosimilars in cancer care will require oncologists to demand just the right amount of data on these products, according to Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance.

In a presentation during the 2019 National Comprehensive Care Network (NCCN) Annual Conference, Lyman said oncologists need enough data to feel comfortable that biosimilars work as well as their reference products, but they cannot expect so much that the cost savings will be wiped out.

“This would defeat one of the primary purposes of their development,” Lyman explained. “But if we don’t require enough [data] while making the approval process easier—prices will come down—it will lower our confidence that adequate due diligence has been done.”

Finding that sweet spot remains a work in progress in the United States, where biosimilars have struggled, Lyman said. He encouraged the oncologists at the NCCN conference

to look to the European experience as a guide. He noted that more than 25 biosimilars have been approved in the European Union since 2006, but the monitoring system had not identified “any relevant difference in the nature, severity, or frequency of adverse effects between biosimilar medicines and their reference medicines” in 10 years.

Both the FDA and the European Medicines Agency require ongoing monitoring of the manufacturing processes for all biologics, which Lyman said is essential to ensure quality and safety.

Biosimilars Are a Means to Improve Access

Much of Lyman’s presentation was aimed at giving those unfamiliar with biosimilars an overview of why these biologics can offer patients access to innovative biologics, including those developed for cancer treatment. He presented data from IMS Health that show global spending on biologics continues to outpace that of spending on pharmaceuticals overall, reaching $221 billion in 2017.

He reviewed FDA evidence requirements for biosimilars as well as the March 2015 approval of the first US biosimilar, filgrastim, sold as Zarxio, a granulocyte colony-colony stimulating factor (G-CSF). Filgrastim biosimilars that reference the originator product, Neupogen, remain among the most common worldwide, although Lyman noted that there are other FDA-approved biosimilars of interest to the oncologist: 1 each for rituximab and bevacizumab and 4 different ones that reference trastuzumab.

He pointed to updated areas of the 2019 NCCN guidelines, using prostate cancer as an example, and showed where different G-CSF products are listed for treatment of neutropenia. The prostate cancer guideline included 2 biosimilar versions of a G-CSF, Zarxio and Nivestym, as well as tbo-filgrastim (Granix), which was approved before the biosimilar pathway existed. It also included 2 products that reference pegfilgrastim, Fulphila and Udenyca.

Lyman also took note of the 2018 FDA approval for Retacrit, which references epoetin alfa, a medication that stimulates erythropoiesis and is used to treat anemia that occurs in chronic kidney disease associated with chemotherapy. The NCCN update in prostate cancer states, “The panel extrapolates that there would be no clinically meaningful difference for treatment of [chemotherapy-induced anemia].”

Transparency Is Key

Lyman explained that physicians remain skeptical about biosimilars and fear that payers or health systems will force their use for cost reasons. The availability of strong clinical data will be essential to ensure that clinicians accept biosimilars, he said.

“NCCN is very concerned that we have access to the data that the FDA have,” he said. Whether the guidelines committees get the data from the FDA or directly from the manufactures, Lyman said, it is essential to have this information so that biosimilars can be integrated into the guidelines going forward.

The naming convention is extremely important because if there are adverse effects, providers will know which biosimilar was used. “If we don’t know or if our patients don’t know what form of trastuzumab was used, that’s an injustice to our patients,” Lyman said.

He pointed to a May 2018 policy statement from the American Society of Clinical Oncology, for which he served as lead author, which discussed naming and regulatory considerations, safety and efficacy, interchangeability, switching, and substitution; the value of biosimilars; and provider and patient education.¹

There’s no question, Lyman said, that “biosimilars will be playing an important role.”

REFERENCE:

1. Lyman GH, Balaban E, Diaz M, et al. American Society of Clinical Oncology statement: biosimilars in oncology. J Clin Oncol. 2018;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893.

The Art and Science of Talking About End-of-Life Care

Toby G. Campbell, MD, MSCI, is a thoracic oncologist and a palliative care physician from the University of Wisconsin Carbone Cancer Center. He began his talk during the final session of the 2019 National Comprehensive Cancer Network (NCCN) Annual Conference with a confession:

“I cannot practice palliative [care] and oncology very effectively at the same time.”

There are moments, Campbell said, when “there is some blend and some blur” between his specialties, but the skill sets are distinctly different. Palliative care takes a different path from oncology and defines success differently.

The goal of his talk, “Navigating the Transition to End of Life Care in Patients With Cancer,” was to help physicians take the dry language of the NCCN palliative care recommendation¹ to help patients “develop prognostic awareness” and turn that into what Campbell called “tools in the tool kit.”

Ultimately, Campbell said, some patients will need a recommendation for hospice, and physicians need to know how to have that conversation. Historically, health systems in the United States have fared poorly at this; the 2015 Institute of Medicine report Dying in America² painted a bleak picture of fragmented care, overburdened families, and care that was often not what the patient wanted. CMS’ Oncology Care Model seeks to address this by requiring every patient with cancer to have a survivorship care plan. But the challenge of the doctor—patient interaction remains because so many physicians were trained in an era when medical schools did not address end-of-life issues.

If the goal is “prognostic awareness,” Campbell said, the conversation must start early. “If we’re going to be talking about dying,” he said, “it really is a conversation that’s best done in bits and pieces.”

Work at the University of Wisconsin is developing phrases to open the door. Phrases are tested—doctors even practice with actors—and once they are fine-tuned, the best methods are studied to measure their effectiveness. Campbell and his colleagues have learned that success starts by laying the groundwork early because success can have a

variety of outcomes.

He showed the audience a slide that plotted out a schedule of 8 appointments, which he said would give a physician a total of 4 hours to discuss palliative care. But more critically, each appointment affords an opportunity to start the conversation at home, during the “spaces in between,” when the real thinking about goals and values takes place. “This will assist in the eventual conversation,” he said.

Add the Question to Appointments

Campbell said the pattern of the typical oncology appointment is divided into 3 parts: discussions of symptoms, scans, and treatment. Analyses of conversations in the middle portion of the appointment, when physicians deliver news that the scans are “good,” “stable,” or “bad,” show that this is the shortest part of the conversation; when news is bad, the treatment segment expands significantly.

Here, Campbell said, is where clinicians must use what he called the blend and “create the space to talk about dying.” The method developed at the University of Wisconsin adds a step between the scan and treatment portions of the appointment to ask, “Would you like to talk about what that means?”

The question should be asked even if the news is good, because if treatment is working, it can extend life, but there could be adverse effects. The idea of shared decision making is critical so that patients and families will always understand available options.

Use Paper-and-Pencil Homework

The development of an “oncology talk tool” is a simple paper-and-pencil chart that shows options for patients and families to consider when one option is to stop treatment. Campbell showed samples of charts that clinicians created that included estimated odds, “0/10” for stopping treatment, followed by “1/10” for a chemotherapy option and “????” for entering a clinical trial. This “best case, worst case” scenario gives patients the critical information to take home and discuss with their families, Campbell said. “This is entirely about the spaces in between,” he said.

In a study that included follow-up at patients’ homes, even after some had died, many families still had the charts. “No one said, ‘I hated that piece of paper they gave me,’” Campbell said.

With Hospice, the Order Matters

Campbell presented a framework for presenting hospice that begins with telling the patient, “I don’t have any more good treatment options left.” Instead of saying the word hospice, describe the nursing and social work services it offers. He suggested that physicians recommend the services first, as a way to give patients care to relieve pain and keep them out of the emergency department, and then say, “It’s called hospice.”

Through testing, Campbell said, “it appears the second strategy is more effective.”

Campbell encouraged physicians to get the patient’s buy-in, reminding them of statements made in previous conversations of their desire to manage pain at home and gaining their agreement to not pursue more treatment. The phrase “How does that sound to you?” is important.

Avoid euphemisms, he said. “The gold standard is to use the word dying.”

The goal is to present hospice as a service available only to people in their circumstances, who want to “focus on living with the time remaining.” Time spent at home with family, in as much comfort as possible as a conscious choice, helps patients realize they have what they need, Campbell said.

REFERENCES:

1. Palliative care. National Comprehensive Cancer Network website. nccn.org/professionals/physician_gls/pdf/palliative.pdf. Published February 8, 2019. Accessed March 24, 2019.
2. IOM (Institute of Medicine). 2015. Dying in America: Improving quality and honoring individual preferences near the end of life. Washington, DC: The National Academies Press.

Aging Population, Rising Morbidity Add to Challenge of Survivorship

Americans are living longer after a cancer diagnosis. Survivorship guidelines are now a well-recognized part of the cancer care landscape; CMS’ Oncology Care Model even requires that each Medicare beneficiary have a survivorship care plan.

That’s the good news.

But there’s bad news, too, according to a nurse and a primary care physician from the University of Colorado Cancer Center, who spoke at the 2019 National Comprehensive Cancer Network (NCCN) Annual Conference.

According to Carlin Callaway, DNP, RN, and Linda Overholser, MD, MPH, cancer survivors don’t always do what they’re told. About 50% don’t wear sunscreen as advised, and 27% do not see a primary care provider (PCP) regularly. An increasing number of survivors have obesity, metabolic syndrome, and other health issues. They don’t always eat healthy or exercise, even though this would increase their chances of survival.

In other words, cancer survivors are aging and come to the cancer journey with more and more comorbidities, just like the rest of the population. But this adds to the challenges of care coordination, what Callaway called “the invisible work” that happens when the care team—PCPs, oncologists, and specialists—works together to keep the patient’s needs from falling through the cracks.

“People are living years with lung cancers, which is wonderful,” said Callaway. “But how do they live with the hypothyroidism and the blood sugar challenges?”

A March 14, 2019, update of NCCN Guidelines for Survivorship includes a revised definition¹ that reflects the fact that guidelines apply throughout the continuum of care and to long-term survivors. Callaway said the University of Colorado advises patients to tell healthcare providers what cancer agents they were given; “for the duration of their life…adverse events may be delayed.”

Immunotherapy has been a game changer for many patients, but it’s not without costs—physical, emotional, and financial, Callaway noted. Intimacy and sexual health may be interrupted. “Our patients have many unmet needs when they finish treatment. Relationships may have changed, for better or for worse. Many people are able to return to work, but many are not.”

The handoff back to the PCP can be emotional; some patients are ready for it, and some don’t want to leave the oncologist. Then there’s the matter of conflict among professional societies over follow-up care. For example, the NCCN recommends that women on tamoxifen have an annual gynecological assessment every 12 months if a uterus is present, but the American College of Obstetricians and Gynecologists (ACOG) says these women are at no increased risk of uterine cancer and require no additional monitoring beyond routine

care, according to an ACOG guideline reaffirmed in 2019.

Survivorship care plans. Callaway said a good plan is simple and easy for the patient to use and the PCP and specialists to find within the electronic health record (EHR). The patient must have control over who sees the plan. Although evidence that survivorship plans improve quality of life is limited, Callaway cited a 2017 study by Spears et al that found when an advanced practice nurse administered the plan, there was an improvement in quality of life and cost-effectiveness. A study from Majhail et al found that plans can reduce stress. A significant review article² highlighting the benefits of cancer survivorship care, including care plans, appeared in the New England Journal of Medicine in December 2018.

The most basic truth about a care plan? “If patients understand their survivorship plans, they are more likely to use them,” Callaway said.

Challenges ahead. As more patients live with cancer, Overholser said, more PCPs are getting questions about life after treatment. And they don’t always feel equipped to answer them, she said, especially questions about the cancer treatment. More and more, PCPs are asked about the psychosocial decisions, and increasingly they deal with the cardiovascular and metabolic aftermath of some therapies.

The healthcare infrastructure must do more to facilitate the movement of patients and information back and forth between oncologists and primary care, Overholser said. There’s not much formal training among PCPs in survivorship care, she said, and a 2017 study by Rubenstein et al found that in 12 advanced primary care practices, cancer survivors were not recognized as a unique subgroup and physicians could not easily identify survivors based on the EHR.

But the biggest challenge ahead is the rising rate of comorbidities. Overholser cited data from BMJ Open that show multimorbidity affects 23% of the general population, including 65% of those who are Medicare eligible. Among those with cancer, the most common conditions were cardiovascular and metabolic: diabetes, congestive heart failure, and cerebrovascular. Overholser said these conditions may be a bigger threat than cancer to long-term survival.

Again, there’s good news and bad news. “Primary care only sees a handful of cancer survivors,” Overholser said. But when it comes to obesity, metabolic syndrome, and high blood pressure, “these are the issues we see every day.”

The most powerful tool that the entire care team has, Callaway said, is patient engagement. If providers can figure out how to harness the desired behaviors of patients, she said, it would be, as neuroscientist Leonard Kish3 called it, “the blockbuster drug of the century.”

REFERENCES:

1. Survivorship. National Comprehensive Cancer Network website. nccn.org/professionals/physician_gls/pdf/survivorship.pdf. Published March 14, 2019. Accessed March 23, 2019.
2. Shapiro C. Cancer survivorship. N Engl J Med. 2018;379(25):2438-2450. doi: 10.1056/NEJMra1712502.
3. Chase D. Patient engagement is the blockbuster drug of the century. Forbes website. forbes.com/sites/davechase/2012/09/09/patient-engagement-is-the-blockbuster-drug-of-the-century/#4d2632155638. Published September 9, 2012. Accessed March 23, 2019.

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