By Martha E. “Meg” Gaines, JD, LLM
For oncologists and their patients on the journey to survival, precision medicine is the most promising development in decades. Yet, as with so many innovations, “the devil is in the details” and the road to precision medicine has significant hazards. There are important challenges along the road to targeted therapies for patient-provider teams to consider as we chart the course together.
Is precision medicine an option?
Availability of effective targeted therapies is sporadic, and changing as new agents are tested. So availability of a proven effective therapy is still unpredictable. Many will be sequenced, few will find value.
With the exception of a very few mutation-sensitive malignancies, providers will be required to try frontline therapy before considering a targeted therapy. Sometimes a targeted therapy can be given in combination with frontline therapy, but too frequently, the common practice is to give the guideline-approved therapy first and wait until it proves ineffective to recommend genomic testing.
The field of targeted therapies is expanding so rapidly that some oncologists are not fully familiar with the opportunities available for targeted therapies, and don’t raise the possibility of genetic sequencing of the tumor soon enough or at all. While patients are increasingly raising the question themselves, it is imperative that practicing oncologists know enough about precision medicine to make it effectively available to their patient partners from the start. While the process is improving, sequencing takes time and the sooner results can be evaluated, the better. Tussling with insurers about coverage can take valuable time as well, so patients and providers should work together to push this along as quickly as possible. At some point, this will become standard practice, but it isn’t yet in many places.
What if no targetable mutation is identified?
Precision medicine is relatively new science; clinicians are often learning alongside their patients about targeted therapies, including immunotherapy, vaccine therapy, etc. Clinician partners must stay true to their essential task: identifying, evaluating, and selecting treatments that best align with the patient’s goals and values. Effective targeted therapies are available for an increasing number of patients, but should not take center stage in treatment deliberations until they become a strong option. Patients don’t want to be a disappointment to our oncologists when our tumors don’t express themselves in an actionable way, and need their continued commitment to our struggle.
Is this affordable?
Testing a tumor sample (biopsy) isn’t always covered by insurance. While the cost is going down as DNA sequencing becomes more widespread, insurance coverage typically lags behind the discovery of new treatments and the associated diagnostic technologies.
The trend is toward insurance coverage, but when there is time, patient-provider teams should verify coverage before agreeing to testing, and explore other coverage options when insurance doesn’t cover these costs. For example, NCI clinical trials typically cover the cost of genetic sequencing, the trial drug and its administration, and travel and lodging once the patient enrolls in the trial.
Coverage varies so be sure to fully explore the cost of the trial to this patient. This may require a very specific conversation with the trial sponsor about what the insurer will cover, what the trial will cover, and what the patient’s responsibility will be. Get as specific as possible about dollars and cents, document the conversation, and send it to the trial administrator just to make sure everyone is on the same page.
What’s out there?
Because targeted therapies are still relatively new, they are not uniformly available in community oncology practices—where 85% of patients get their care—or even in academic medical centers. Clinicians and patients should look broadly at the options for targeted therapy that may be available after reviewing the genomic sequencing results. Understand that what a particular institution offers may not represent all that is available to treat this cancer, and encourage interested patients to focus on the nature and promise of the trial for their cancer over less important details, such as its location, where they are not a practical restriction. Clinicaltrials.gov is a good place to start the search.
It takes time to identify and be evaluated for participation in a clinical trial, and time is of the essence to most patients with cancer. Be an assertive team, call early and often, go get and send the medical records yourselves if that’s faster than the inter-institutional transfer process. Anticipate the need for records and have them ready to go at a moment’s notice. When precision medicine becomes a more paved road, more efficient systems will come along, but until then clinician-patient teams do well to advocate effectively for the most promising care.
Is this available to everyone?
Insurance coverage variability, access to high-quality care, and the need to self-advocate raise a serious issue, namely that many people—particularly those already marginalized by a lack of education and resources—will not be in a position to know about and advocate effectively for inclusion in this promising new treatment arena. The costs associated with finding opportunities, travel to be evaluated, and long stays in faraway cities for treatment effectively prohibit many from participating and exacerbate existing disparities.
Clinicians must commit to eliminating the profound injustice of disparities, and make access equity a cornerstone of continued research. This will require intentionality about offering new and innovative treatment options to all patients equally, a support infrastructure within their practices to facilitate access, and creativity and persistence from the navigators that staff them. Many manufacturers of targeted therapies have programs providing their drugs at no cost to patients whose insurers deny coverage and to those without insurance.
Finally, clinicians would do well to partner with patient advocates to secure legislative changes necessary to support equitable access to precision medicine.
Is this a miracle?
Targeted therapies offer some hope in some cancers that have been particularly resistant to treatment. Some are curative, but so far most are not. Targeted therapies, like other cancer treatments, often have significant side effects. Sometimes these are not yet well known or understood; long-term side effects are particularly difficult to predict this early. Patients who choose these therapies typically do so because other good options do not exist; there is a chance they will extend life significantly—sometimes by years—but not indefinitely.
Is this opening Pandora’s Box?
As genomic sequencing of tumors as well as genetic testing for inherited mutations gains popularity, an individual’s decision to learn more about predisposition to certain diseases and treatments may have a far broader impact than intended. Testing positive for an inherited mutation associated with elevated cancer risk means that others in the patient’s family may have it as well, and may not be particularly interested in knowing about it. As testing becomes more prevalent, we will need to develop better ways to help people navigate the complex waters of genetic information management. This will require, at the very least, effective educational materials to make the information comprehensible to the general population as well as the development of cultural norms and understandings to guide the decision to test and the process of sharing the results.
The mapping of the human genome spawned the development of precision medicine and ushered in an extraordinary new age in oncology care. With these developments comes an opportunity—a need—for patients and their clinicians to partner in previously unprecedented ways, to join together as learners in this brave new world.
Professor Gaines is a distinguished clinical professor of law at University of Wisconsin Law School and is the director of the University of Wisconsin Center for Patient Partnerships. Follow her on Twitter @MegGaines1.