September 2018 Edition Vol.11, Issue 9

Overcoming Obstacles in Delivering Precision Oncology

By Lynne Lederman, PhD

ASCO President and cancer survivor Bruce E. Johnson, MD, chose “Delivering Discoveries: Expanding the Reach of Precision Medicine” as the theme of his presidential year. Precision medicine, often described as giving the right treatment to the right patient at the right time, has dramatically transformed the care of patients with cancer. In oncology, precision medicine means characterizing patients’ tumors, treating them with the most effective agents, and continuing to find ways to improve the efficacy of treatments.

As Dr. Johnson noted in his presidential address, advances in precision oncology have improved patient survival and quality of life. Although patients with certain types of cancers have benefited from precision medicine more than others, efforts continue to expand the scope of precision oncology.

Continuing interest in this field was reflected not only in the meeting’s theme, but also in three educational sessions presented that focused on overcoming obstacles and integrating precision medicine into practice. Some of these obstacles included implementing precision medicine trials in the community setting, managing expectations, and helping patient advocates in decision-making roles learn more about the current state of precision medicine in oncology.

We look at some hurdles in the way of delivering precision oncology to all patients, particularly those in the community setting, and suggestions for moving forward.

Identifying Strategies for Precision Medicine Trials

Edward S. Kim, MD, Levine Cancer Institute, Charlotte, NC, an academic-community hybrid system, chaired the education session, “Overcoming Unique Obstacles to Implementing Precision Medicine Trials in the Community Setting.” He spoke on identifying strategies and best practices for precision medicine trials.

In reacting to some recent negative press alleging that results from the NCI-MATCH (Molecular Analysis for Therapy Choice) trial imply that precision medicine doesn’t work, he pointed out the importance of understanding the difference between research and clinical practice. “What we have learned from trials like NCI-MATCH is that it is tough to do these types of studies. The match rate will be low,” said Dr. Kim. Reporting negative results is important so that physicians in the community may be less tempted to test unproven treatments on their own in the absence of data.

Dr Kim doesn’t think getting a 500-gene assay of all an oncologist’s patients off-study would improve survival but does agree that precision medicine improves survival and quality of life for patients with cancer.

In cancers like breast, lung, and CML, where biomarkers are matched with targeted therapies, patients can be treated with biologic or hormonal therapies in lieu of chemotherapy. Dr Kim thinks this has made a huge impact with precision medicine in oncology, “but that’s not [for] the majority of patients.”

He acknowledges that generalist oncologists in the community setting, particularly in rural areas, may not know what tests to order and don’t have anyone to talk to. Clinical guidelines or pathways may help inform these doctors. “That’s why ASCO has showcased this type of session the last couple of years because it is so important to get the message out,” he said.

Dr. Kim thinks the biggest hurdle to precision oncology is a lack of organizational leadership. There needs to be agreement on the testing platform, whether in-house or commercial, and a venue organized to discuss the results, i.e., a multidisciplinary tumor board that includes surgeons, pathologists, and medical and radiation oncologists.

He also recommends the use of checklists characterizing quality research and quality medicine, e.g., the ASCO QOPI (Quality Oncology Practice Initiative) program. “That is how it has to start, with the checking of some of these boxes and deciding that’s the direction you want to go.”

Implementing Precision Medicine Trials in the Local Community Setting

Lora Black, RN, MPH, OCN, CCRP, Sanford Research, North Sioux Falls, SD, discussed technologies and resources for implementing precision medicine trials in the community-based setting. Her healthcare system’s first hurdle was making sure they could obtain tissue and get it to vendors for molecular testing in an appropriate time frame, so they could influence patient care without a long delay.

Once they knew it was feasible to ensure obtaining enough biopsy tissue or archived pathology samples, the next step was to review the molecular profiling results. Steven Powell, MD, at the cancer center, championed a genomic tumor board and a multidisciplinary conference to review cases and discuss profiling test results to make treatment recommendations and educate the entire team.

Sanford wanted to standardize capturing whether an on-label or off-label treatment or clinical trial was available for the patient. “Most importantly,” she said, “we wanted not only to be able to do the test but to be able to offer a personalized or genomically matched treatment in our community setting. The hurdles we have in the community are much different in that, especially in this part of the world, we have been known as fly-over territory.”

This meant proving they could obtain tissue for molecular testing, explaining their 30-plus year history of conducting clinical trials, and “telling our story in enough of a way that we were able to get some of those larger trials in the community setting.” Sanford was able to participate in the My Pathway (NCT02091141) trial and was one of the five top-recruiting sites along with academic centers.

Once precision oncology was implemented at Sanford, their genomic steering committee has become the core of the program. Ms. Black said, “It’s the group that keeps pushing us forward as things continue to change.” A full-time precision oncology project manager works between the clinical and research teams, helps manage genomic tumor boards, and works with the nurse navigators to help screen patients.

Finally, Ms. Black said, “We even started to look at how we can use telemedicine for clinical trials to go a step further and get clinical trials into the smaller communities.”

Next Generation Sequencing

Leonard Saltz, MD, Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center, New York, NY, gave an education session presentation on managing expectations and managing costs: optimizing the value of next generation sequencing (NGS) in cancer care. Originally intended to be a debate about whether NGS was right for every patient, the discussion changed with the FDA approval of an NGS assay as a companion diagnostic for a tumor-agnostic treatment based on the molecular characteristics of the tumor rather than the tumor type, as well as a (somewhat open to interpretation) national coverage determination issued by CMS.

Dr. Saltz said his goal was to help people maintain a balance between optimism and realism, and to understand the strengths of precision medicine, and to understand where we are not yet. “To some degree the nature of precision medicine is extinguishing itself, in that once we find a highly actionable target, it becomes standard practice,” he said, adding, “I think it’s important to understand that precision medicine is simply a continuation of what has come before and what will come after it, trying to match the right patient with the right treatment.”

Obstacles in the way of practicing precision medicine appropriately include losing sight of the fact that sequencing every tumor for previously unexpected and unidentified targets is experimental. For the rare mutations in which potential treatments have been identified, the challenge will be how to screen thousands of patients to find the one who might benefit. As NGS becomes cheaper, it will still yield huge amounts of data, and the test may not be reimbursed. Further, not all targeted therapies are effective in all patients with the targeted marker.

Furthermore, Dr. Saltz commented, “We can have highly statistically significant benefits that are clinically irrelevant. What we are looking for is one of those situations where we don’t need a statistician to tell us the drug worked or not, where it’s obvious.”

The Patient Perspective

There have been a few sessions at ASCO considering the patient perspective, mostly focused on collecting patient reported outcomes and the need for and means of discussions of financial issues and survivorship. These sessions are, understandably, not given by patients or advocates, so we turned to an advocate organization to hear the patient voice.

The Research Advocacy Network (RAN) held the Precision Medicine Clinical Trials in Oncology Symposium for advocate members of the NCI Steering Committees at the National Clinical Trials Network Advocates in November 2017. The purpose was to help patient advocates in decision-making roles learn more about the current state of precision medicine in oncology, and to gather input on the design of future precision medicine trials.

According to RAN co-founder Mary Lou Smith, JD, MBA, “We were trying to get a feel for what precision medicine meant to patients. One issue is managing expectations. The thought is that in individualized treatment, if I have this mutation or alteration and you give me a drug targeted at it, I’m going to benefit.” This is not always the case.

Access to molecular tumor profiling and reimbursement for those tests varies. A major problem for patients is being off treatment during the wait time from biopsy to receipt of test results. Ms. Smith pointed out that patients may be very excited about the possibility of receiving a specific, targeted treatment rather than chemotherapy, but what happens when there isn’t a match? Even if specific genetic alterations or mutations are identified, they may not be actionable.

Being told “there’s nothing for you is very hard to accept as a patient,” Ms. Smith reminds us. “What are you going to do then? You now have a person who was willing to go into a clinical trial, so do you find another trial for that individual to give them hope, or do you tell them to get their affairs in order? It’s a difficult situation.”

Ms. Smith said, “I think the focus on having the patient understand what it is they are getting into and how it might help their particular case would be good.” This would include what kind of information will be obtained from testing and how that information realistically could affect the outcome of their care.

“We talk about individualization, but how individualized is it and how much are they asked about their quality of life, the toxicities they may experience?” Patients don’t always know what to ask, so designing some questions for the patients to ask their physicians might go a long way in increasing their understanding.

Additional Resources

Powell SF, Dib EG, Bleeker JS, et al. Delivering precision oncology in a community cancer program: results from a prospective observational study. JCO Precis Oncol. DOI: https://doi.org/10.1200/PO.17.00220 Published online on ascopubs.org/journal/po on May 11, 2018.

The Precision Medicine Clinical Trials in Oncology Symposium proceedings: http://www.researchadvocacy.org/sites/default/files/docs/PrecisionMedicineSymposiumProceedingsFinal-2.pdf and videos of sessions: http://www.researchadvocacy.org/precision-medicine-symposium

ASCO’s Research Community Forum: Annual meeting, tools, and other resources https://www.asco.org/research-progress/research-community-forum

The Quality Oncology Practice Initiative (QOPI https://practice.asco.org/quality-improvement/quality-programs/quality-oncology-practice-initiative

Proposed Decision Memo for Next Generation Sequencing (NGS) for Medicare Beneficiaries with Advanced Cancer (CAG-00450N) https://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=290&bc=AAAAAAAAAAQAAA%3D%3D

Post a Comment

OBR Archives

To view previous issues of OBR green contact you can visit our archives. The entire library of OBR green articles is searchable.