For people with advanced cancer, making sense of the complexities of cancer treatment can be truly daunting. Enter the oncology nurse navigator (ONN), a nurse with specialized training to help patients overcome any barriers they may face in accessing high-quality cancer care. At Cancer Commons, our Director of Patient Services Deb Christensen, MSN, APRN, AOCNS, OCN, applies her ONN training to ensure that every patient receives the guidance they need. Here, our Curious Dr. George asks her about her work.

Curious Dr. George: You are in charge of patient services at Cancer Commons. How would you describe how you use your ONN skills every day to assist patients with advanced cancer who seek help at Cancer Commons?

Deb Christensen, MSN, APRN, AOCNS, OCN: My first real exposure to oncology was as a nurse navigator in a large healthcare organization. Care coordination is one of the main roles of the ONN. Networking and forming partnerships with other departments and physician offices was key to successfully helping people navigate the complex landscape of oncology care. I had the opportunity to participate on a committee of nurses who updated the Oncology Nursing Association Nurse Navigator Competencies in 2017 and was coeditor of Oncology Nurse Navigation: Delivering Patient-Centered Care Across the Continuum (second edition).

These experiences allowed me to share my passion for the role of the ONN and grow in the profession. After working as an ONN, and then serving as the system lead for the navigation program, I retired from the organization and joined Cancer Commons as a nurse navigator.

I am peoples’ first point of contact at Cancer Commons. I assist people through the registration process and then contact them to learn more about their cancer history and assess their needs, goals, and expectations. An essential ONN skill that I use consistently is the ability to communicate in a way people can understand and follow. Our patient navigation specialist, Lauren Levine, and I assist the patients and their families with retrieving medical records, collaborating with our Scientists, and checking in at key points in the cancer journey. Our goal is to make the entire process personalized and as simple as possible. The entire Cancer Commons team collaborates to help clients create a plan to discuss with their local oncology team. This action plan is complimentary, informed by the latest scientific research, and curated by PhD scientists.

My new role as Director of Patient Services evolved out of the Cancer Commons team’s desire to provide a more personalized experience to clients and offer new services. Our team helps clients understand their treatment options and take potential next steps. Additional services being implemented include a Cancer Commons Plus subscription for ongoing follow up and communication with the science team, clinical trial enrollment assistance, and other assistance offered by the hour. The ability to put clients first by providing non-biased treatment options and timely compassionate care is at the heart of everything we do at Cancer Commons.

Deb can be reached at deb.christensen@cancercommons.org.

The existing drug development system “has failed miserably” for people with glioblastoma brain tumors, according to Al Musella, DPM, President of the Musella Foundation for Brain Tumor Research & Information, Inc. In partnership with Cancer Commons, his organization’s Brain Tumor Virtual Trial aims to speed discovery of promising new glioblastoma treatments.

Curious Dr. George: How might your Virtual Trial approach speed the process toward either validating or invalidating potential therapies for glioblastoma?

Al Musella, DPM: I have watched how the current drug development system works since 1992, and think we could do much better. There are many problems but the top ones, as they relate to malignant brain tumors, are:

1. The current system is set up to try to find one magic bullet that will successfully treat the disease. This concept has worked reasonably well for some diseases, but for brain tumors it has failed miserably. I feel that the ultimate cure for brain tumors will be a combination approach, and under the current system, it is very difficult to get the individual components of that ultimate cocktail approved by the U.S. Food and Drug administration (FDA).
2. There are not enough patients for the number of trials needed. About 10% of adult glioblastoma patients—about 2,000 per year—enter clinical trials. There are currently 318 glioblastoma trials open for enrollment, which means only six patients are available per trial per year. And some trials require large numbers; it takes years to accrue enough patients, and many trials never do.
3. Phase 3 trials are too long and inflexible. In the last 25 years, only one phase 3 glioblastoma study showed a statistically significant improvement in survival, adding only 3 months to median survival. As patients are treated, we learn how to use the treatments better, but the rigid structure of a phase 3 trial doesn’t allow for modifications midstream. Rather than stop a trial, discard the results and start over, researchers complete a trial anyway, knowing that there may be a better way to use the drug.

I propose an alternative approach:

1. All patients must be watched in a regulatory-grade registry so we learn from every patient—not just the 10% who may not even represent the typical patient.
2. A formal randomized trial is perfect to prove that a combination works, but we are not yet at the point where we have a combination worthy of a full-scale phase 3 trial. So, if a patient desires entry into a formal trial, I propose they be given access to the registry to pick the most promising trials.
3. We need a system in which experimental treatments get fast conditional approvals when they are shown to be relatively safe, with early evidence that they have the intended effect—even if that effect doesn’t result by itself in prolonged life. This allows us to use them in combinations and figure out how best to use them.
4. Paying for medical drugs is a problem. The only way this can work is if patients do not have to pay high costs for their treatments, and if drug companies get paid for the treatments. This will allow access to the drug. The Virtual Trial system should keep drug costs down, as it will take the vast majority of time and money out of the drug development process and break the monopolies currently preventing many new drugs from being developed. In fact, I have proposed a bill (see below) that basically requires Medicare and Medicaid to pay for them and encourages private insurance to pay. We are working out the exact wording and are considering a “pay for performance” model, or a compromise in which costs for non-standard treatments cannot exceed what the standard of care would have cost.
5. Doctors, or teams of researchers, can then think up the best combinations for each individual patient, and test them in small, fast, inexpensive (or free) virtual trials. They can see the ongoing results in all patients and quickly determine if a conditionally approved drug is worthy of continued usage—perhaps tweaking how it is given or the combinations used, or if it should be dropped. Once the ultimate cocktail is found, it can then be tested in a formal phase 3 trial.

I have been working on the components of this plan. We already have “right-to-try” laws passed in the U.S., but these did not work out as intended, mainly because of cost issues and fear that the FDA would hold usage of this pathway against a drug company. So, I am now working on a much-improved version of early access called the “Promising Pathway Act,” which was recently introduced into Congress. It fixed most of the problems with right-to-try laws and the FDA’s Accelerated Approval Program. It provides for conditional approval of treatments and requires all patients who use any conditionally approved drug to participate in a registry.

My organization, in partnership with Cancer Commons and its for-profit spinoff xCures, has set up a patient-navigation program that should be the model for how we approach all serious diseases. Our team of neuro-oncologists, PhD researchers, and nurse navigators—aided by an artificial intelligence engine—can look at our rapidly growing patient registry (we now have over 1,250 patients) and evaluate medical research, the rationales presented in tumor board meetings, and patients’ medical histories in order to come up with a list of treatment plan options that may be best for any given patient. The patient and their own doctor can select a treatment from our list, or they can elect to try whatever other treatments they want. Whatever they choose, our team then follows up on every patient to see the outcome of their chosen treatment. This way we learn from every patient.

We try to help patients get access to their chosen treatments, but the most promising options are usually impossible to access because the components are not yet approved, and either they are unavailable under expanded access or the drug companies won’t allow us to combine the experimental drugs.

Nonetheless, any doctor or researcher who is using a new combination of FDA-approved drugs for a patient can submit that treatment plan option to our system to be run as a virtual trial, allowing the doctor or researcher to quickly test the theory in their patient and use our system as a screening tool. They can try many combinations quickly, and if a particular combination shows a lot of promise, it can then be promoted to a traditional phase 3 trial to validate the findings.

Any treatment plan options validated in this way would be made up of FDA-approved treatments, so any doctor could prescribe them, allowing every brain tumor patient to have access—not just those perfect patients that fit into existing clinical trials.

In summary, our Virtual Trials could be used as a screening tool to figure out the best combinations, and how best to use treatments, which then can be tested in formal trials. Conversely, this approach could be used to quickly eliminate bad combinations. Having all results available in a central registry would help doctors from around the country avoid trying the same ineffective combinations.

Dr. Musella can be reached at musella@virtualtrials.org.

Curious Dr. George
Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column.

Richard B. Schwab, MD

Professor of Medicine – Division of Hematology/Oncology; Medical Director, Koman Family Outpatient Pavilion Infusion Center – UC San Diego Moores Cancer Center

For most people with breast cancer, a lump is the first sign that leads to diagnosis. But some cases are not detected until after spread has already occurred. Here, our Curious Dr. George asks Richard B. Schwab, MD, how he would approach such a case if his own wife were the patient. Dr. Schwab is Professor of Medicine in the Division of Hematology/Oncology and Medical Director of the Koman Family Outpatient Pavilion Infusion Center at U.C. San Diego Moores Cancer Center.

Curious Dr. George: How would you, as a breast cancer expert, manage your wife’s cancer if it were to present as shortness of breath or back pain, with a breast mass only then detected?

Richard B. Schwab, MD: Doctors frequently take care of their family members for minor problems; cancer is not one of them. Even caring for patients, managing one’s own anxiety about the normal uncertainties of medicine is not easy. Managing of my wife’s cancer would not be possible, so I would have one of my excellent colleagues be her oncologist.

That said, I would be answering my wife’s questions about this frightening situation and trying to guide her. She gets her screening mammogram every year, so presenting with metastatic breast cancer would be very unusual. Only 5% of breast cancer is de novo metastatic, and many of these patients did not have recommended screening before diagnosis. However, screening mammograms are not perfect, so your hypothetical scenario is possible.

If she was short of breath, I think we would utilize the emergency department. Although cancer is usually a relatively slow process, there are rare times when patients can become very ill during the normal time required for diagnosis and treatment initiation. CT scans can be done quickly and could identify a pulmonary embolism, pleural effusion, or lymphangitic spread. Starting appropriate therapy quickly (anti-coagulation, thoracentesis, or chemotherapy respectively) could be critically important.

Making a pathologic diagnosis would be the next step, and would radically alter treatment (and life) plans. Breast cancer is not one disease. Oddly we would be hoping for an aggressive estrogen receptor-negative and HER2-positive cancer. These cancers are highly responsive to numerous treatments, and cures—even with metastatic disease—are becoming more and more common. A triple-negative cancer would be complicated. Some patients with triple-negative breast cancer, particularly limited to the lungs, do end up cured, but these cases are rare and overall this type of breast cancer has the fewest treatment options. Last but most common, particularly if her cancer had spread to the bones, would be estrogen receptor-positive disease. These cancers generally grow more slowly and on average patients survive longer with this type of disease. However, these cancers are never truly cured, although for older patients lifelong disease control can sometimes be obtained. For a patient as young as my wife new therapies would be needed to have any reasonable hope of lifelong disease control.

Which location to biopsy is a common challenge we would need to address. Biopsy of the breast is the easiest, but may not reflect the more dangerous disease that has spread to other organs. Lung biopsy has some additional risk, it is anxiety provoking, and sample quantity (or even successful sampling) can be challenging. Biopsy of the bone, while very safe, can give unreliable results due to the need to decalcify the sample prior to testing. The details of the patient’s case and the expertise of the doctor performing the biopsy matter. Having expert trusted colleagues in radiology and pulmonology would be a significant advantage for my wife.

I mentioned the idea of truly curing my wife. I define true cure as a lack of cancer progression for at least 5 years after stopping therapy. I have cared for many patients with metastatic disease that has been cured, and that knowledge would help my family get through what is fortunately only a hypothetical situation.

Dr. Schwab can be reached at rschwab@health.ucsd.edu.

Curious Dr. George
Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column.

Pauline Funchain, MD

Director of the Melanoma Medical Oncology and Genomics Programs at Taussig Cancer Institute, Cleveland Clinic

Cancer patients often ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Cleveland Clinic oncologist Pauline Funchain, MD, how she would handle her own diagnosis of advanced melanoma.

Curious Dr. George: What would you do if you personally were discovered on a routine exam to have abnormal liver function tests that led to scans and the finding of several liver masses? Remembering back some 15 years, you had surgery to remove a 7-mm-diameter, 2-mm-thick melanoma from the skin of your lower leg, treated by wide excision with clear margins. No spread detected at that time. No tumor testing then, aside from light microscopy. How would you proceed?

Pauline Funchain, MD:

Starting line: First, I would take a deep breath. I would remind myself that stage IV melanoma of the skin has become a disease state that can have durable remissions well over 5 years, and that such remissions are not rare. I would be heartened knowing that results approaching cure are possible for some stage IV melanomas.

Next, I would contact my nearest academic medical center. I would carefully research teams known to have good bedside manners, clear communication, and melanoma expertise. The field of melanoma is rapidly changing for the better, and I would want a team that is not only well aware of these developments, but also would be able to clearly explain the multiple therapy options available to me in the context of a briskly moving field. Lastly, I would prefer a medical center where medical subspecialists were readily available and accustomed to timely multidisciplinary communication, as immune-mediated adverse events (irAEs) are commonly elicited during the course of systemic therapy for melanoma.

Workup: At this center, I would first undergo a biopsy of a liver mass. I would ensure BRAF mutation screening was performed by immunohistochemistry (IHC), the most rapid of available BRAF testing modalities. If enough tissue was available, I would send for next generation sequencing (NGS) of the tumor specimen, to prepare for possible second- or third-line therapies. If I had a family history of cancer, personal history of multiple cancers, or was relatively young, I would see a genetic counselor to discuss germline genetic testing. For staging I would get either a CT chest/abdomen/pelvis or PET CT. MRI brain is absolutely essential, as brain metastases are common, often asymptomatic, and may influence first-line therapy choices.

First-line therapy: With staging complete, I would inquire about first-line immunotherapy-based trials. While the best outcomes for stage IV disease, particularly involving liver and/or brain, have been seen with combination ipilimumab/nivolumab, I would welcome the opportunity to try something new in a rapidly evolving melanoma treatment landscape. I would be reassured knowing that all gold standard therapies would still be available to me should a first-line clinical trial fail. If I was not eligible or did not like available clinical trials, I would proceed to first-line treatment with ipilimumab/nivolumab. If I had a personal history of autoimmune disease, I would request a consultation with the appropriate medical subspecialty prior to starting immunotherapy. Other medical conditions might influence me to prefer single-agent immunotherapy, and it is these situations that highlight the importance of having a medical team who is able to have a careful discussion with me to understand my individual needs.

While on therapy I would undergo systemic imaging every three months to assess response to therapy. If my original staging did not demonstrate brain metastases, I would undergo MRI brain every 6 months in the stage IV setting. If I had fast-growing disease, was rapidly losing weight, had a very large burden of disease, or some combination of these factors, I may prefer to invoke the rapid response typically seen with targeted BRAF/MEK therapy. On targeted therapy, I would consider imaging every 2 months, given a higher likelihood of developing therapeutic resistance with the combination of factors that led me to start targeted therapy. I would follow my status closely with serial LDH levels, which correlate well with BRAF-mutant disease burden.

Closing thoughts: In the landmark trial of first-line combination immunotherapy for stage IV melanoma, median melanoma-specific survival has not yet been reached after 6.5 years of follow-up. In plain English, more than half of those who underwent combination immunotherapy have survived stage IV melanoma at the 6.5-year mark. Because not everyone experiences prolonged survival, I would be realistic about having a stage IV cancer diagnosis that might be fatal, yet remain optimistic given the pace of new drug development that immunotherapy and targeted therapy have precipitated in the last decade.

Requests for Dr. Funchain’s email address can be sent to Curious Dr. George at gdlundberg@gmail.com.

Curious Dr. George
Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column.

Lea Ann Browning-McNeeDirector of Communications & Stakeholder Engagement at the Reagan-Udall Foundation for the FDA

 

Susan C. Winckler, RPh, Esq. CEO at the Reagan-Udall Foundation for the FDA

 

For some advanced cancer patients, the best course of action may lie beyond standard treatment options. Some of these patients can enroll in clinical trials that investigate promising new treatments. But others may find their best option is to apply for individual “expanded access” to an investigational treatment.

Here, our Curious Dr. George asks two leaders from the Reagan-Udall Foundation for the Food and Drug Administration (FDA) how their organization supports the FDA by striving to facilitate patient access to investigational products:

Curious Dr. George: The goals and process of “Right to Try” legislation have blended with existing policies and practices of expanded access to investigational treatments for patients beyond standard of curative care—especially for those with cancer. How does the Reagan-Udall Foundation for the FDA help physicians better serve their patients’ needs by more easily navigating expanded access, including use of institutional review boards (IRBs) for Investigational New Drugs (IND) for individual patients?

Susan C. Winckler, RPh, Esq. and Lea Ann Browning-McNee, MS, of the Reagan-Udall Foundation for the FDA: Expanded access, sometimes called compassionate use, provides a pathway to investigational treatments not approved by the FDA for patients who have serious or life-threatening illnesses and cannot participate in clinical trials. Single-patient expanded access allows a treating physician to request an investigational product from a pharmaceutical company on behalf of an individual patient. Typically, FDA approves close to 99% of single-patient expanded access requests.

FDA and its Foundation, the Reagan-Udall Foundation for the FDA, are working to make it easier for physicians to navigate the process and better serve their patients by creating new tools to simplify and de-mystify the process.

One such tool is Project Facilitate, created by FDA’s Oncology Center of Excellence as a single point of contact for physicians (and their healthcare teams) who have questions or simply want help submitting a request for their patient. Project Facilitate staff answer questions via phone or email and walk the physician through every step of the process.

Another new tool, Expanded Access eRequest, launched last year by the FDA Foundation and experts at FDA, moves the request from paper or fax to an online app. eRequest takes physicians screen-by-screen through the expanded access application process — from determining if expanded access is appropriate for their patient to submitting the request to FDA. It even sends reminders to let physicians know when follow up reports should be submitted. And the app’s home on the FDA Foundation’s Expanded Access Navigator website means physicians can identify potential investigational therapies; access sponsor (pharmaceutical) information; complete, sign, and submit the request form (FDA form 3926); and upload supporting documentation all in one place.

There are important considerations to bear in mind before pursuing any investigational treatment—whether through a clinical trial or expanded access. In addition to practical considerations like travel and treatment costs, there are medical considerations, including potential risks and unknowns of the investigational treatment, the severity or stage of illness, comorbid conditions, and the likelihood that the treatment will be effective. That’s where the Institutional Review Board (IRB) Curious Dr. George references comes in. The IRB is a committee of medical and ethics experts along with community or legal representatives who review and approve biomedical research involving patients. Even though expanded access is considered a treatment and not formal research, the IRB wants to be sure all patient safeguards are adhered to because an investigational product is involved. One such safeguard is informed consent, which helps ensure patients have details about the treatment protocol that clearly defines expectations, foreseeable outcomes and risks, and patient rights.

The patient, physician, IRB, FDA, and sponsor all need to agree that expanded access to a particular product is right for the patient. Each of these voices and perspectives is important. The company, for example, may not approve a request for a variety of reasons, such as simply not having enough of the investigational product available. A patient might, after considering all the information, choose not to pursue it. The overall expanded access process is intended to help each party understand the situation, and then decide about going forward.

FDA continues to simplify the expanded access journey for physicians and, ultimately, their patients. You can learn more on the Expanded Access Navigator.

Ms. Winckler can be reached at swinckler@reaganudall.org and Ms. Browning-McNee at lmcnee@reaganudall.org.