In addition, official approvals have recently been granted for precision medical drug delivery, which is independent of the location of the cancer. Sensible use of the particular antineoplastic requires the documented presence of the specific molecular target. Examples include a host of mutations within tumor cells suggesting the potential benefits of checkpoint inhibitors and the presence of an unstable molecular signature from microsatellites, similarly pointing to the potential benefits of this class of immunotherapeutic drugs. While the current impact of the precision medicine revolution has been argued by some as being overly hyped,2 others have made strong arguments against this conclusion.3
However, it cannot be assumed that the promise of precision medicine will follow regulatory decisions at the individual patient and physician level. Rather, it is up to drug manufacturers to market the use of targeted therapeutics in specific clinical situations and molecular diagnostics companies to promote FDA approval of their platforms as options for tumor-diagnostic approaches in disease management.
There may be potential dissociation between clinical trial data, regulatory approvals, and recommendations from the medical or insurance company for obtaining the molecular information essential to deliver a targeted therapeutic, and the “real world” of outpatient oncology care in the United States. This was highlighted in a recently published report examining the medical records of women with ovarian cancer and the percentage of which was subject to a germline test for the presence of a. had undergone BRCA Mutation.4th The results of clinical germline tests for patients in Georgia and California were linked to surveillance, epidemiology, and end-result data for people diagnosed with breast or ovarian cancer between 2013 and 2017. Only 34.3% of 14,689 ovarian cancer patients had received a germline test.4th
This rather worrying finding came despite the fact that for several years several national medical organizations and widely recognized medical regimens have strongly recommended that this information be obtained in order to assess the potential risk of breast and ovarian cancer in family members of patients with a diagnosis of cancer. A low germline test rate is also increasingly observed in patients with prostate and pancreatic cancer. In addition, it has been shown that prophylactic surgical procedures (e.g. bilateral oophorectomy, mastectomy) can reduce the risk of later malignancies BRCA Mutation carrier.
Finally, recently published results from the Phase 3 study have shown the great benefits associated with the administration of PARP inhibitors as a maintenance treatment approach in women with ovarian cancer who BRCA Mutation positive. Despite the ample evidence of the clinical benefit associated with obtaining this specific germline (and somatic) mutation data, there is a clear discrepancy between what is clearly optimal care and the reality of clinical oncology in the real world.
A number of possible reasons for these disturbing results can be cited, beginning with the observation that the pace of change in our understanding of the biology of individual cancers and the corresponding modification of our therapeutic arsenal continues to accelerate. This condition makes it increasingly difficult for non-tumor specific oncologists to keep abreast of the spectrum of various modifications in disease management. The academic oncologist who specializes in understanding the biology and treatment of an individual cancer (e.g., breast cancer) or a group of malignancies (e.g., gynecological cancers), or a member of a large oncology group practice that may have a Has similar opportunity to affect a limited number of diseases will almost certainly be in a superior position to cope with these rapidly growing changes.
However, for the generalist routinely responsible for treating multiple cancers on a given day, keeping up with changes in treatment, especially with new molecular-based therapy options, can be daunting.
While oncologists will certainly never deliberately deny their patients the best possible care, the outcome may be the same if they are not informed of new developments, do not have time for regular updates, or have no accessible, robust decision-making aids that can help them understand best practices a specific clinical situation.
When deciding on a precision medicine approach, it must be emphasized that it increasingly requires next-generation sequencing rather than a single test for a specific molecular anomaly. There are other aspects to consider when implementing this extended molecular test strategy.
There are many questions that should be asked. Of the many available, which test platform is optimal in a particular practice? Does the insurance company pay for such tests? How easy are the reported results to interpret? What decision support tools does the company make available to the clinician? How realistic are clinical studies (e.g. geographical location, selection criteria) for an individual clinician and patient that can be suggested by the molecular results?
Complicating the test is a situation where the results suggest that off-label use of a commercially available antineoplastic might be useful. How does the doctor get insurance company approval or possible compassionate use of the drug by getting it from the manufacturer? If an oncology practice has little or no experience in this area, the learning curve and the time and effort required for a single agent can potentially be a significant barrier. Here, too, it is not the doctor’s lack of will to help the patient, but objectively pragmatic concerns in dealing with an often complex and unclear bureaucracy.
And when the doctor fails to find a potentially promising drug, it is easy to imagine how that disappointment will affect the patient and the patient’s care team.
- Shaw AT, Bauer ™, de Marinis F, et al .; Investigator of the CROWN study. First-line therapy with lorlatinib or crizotinib for advanced ALK-positive lung cancer. N Engl J Med. 2020; 383 (21): 2018-2029. doi: 10.1056 / NEJMoa2027187
- Prasad V. Perspective: the Precision Oncology Illusion. nature. 2016; 537 (7619): S63. doi: 10.1038 / 537S63a
- Subbiah V, Kurzrock R. Debunking the illusion that precision oncology is an illusion. oncologist. 2017; 22 (8): 881-882. doi: 10.1634 / theoncologist. 2017-0040
- Kurian AW, Ward KC, Abrahamse P, et al. Trends in time in receiving genetic germline tests and results in women diagnosed with breast or ovarian cancer. J Clin Oncol. 2021; 39 (15): 1631-1640. doi: 10.1200 / JCO.20.02785