Lynn Nye, PhD
December 2019—Presentations at the recent Cancer Biomarkers Conference IV, sponsored by the University of Mississippi Medical Center, prompt reflection on how far we have come since the introduction of Rituxan, the first monoclonal antibody to be approved by the Food and Drug Administration for the treatment of cancer in 1996. Before the launch of Rituxan, physicians were skeptical about the efficacy and safety of monoclonal antibody therapy because of the history of failures. In the early days, nurses had to learn how to manage the short-term side effects related to the IV infusion. But patients, many of whom I met, had exhausted all of their treatment options for non-Hodgkin lymphoma, and Rituxan gave them a new lease on life. At the time, because of the skepticism, it was hard to see the big opportunities for monoclonal antibody therapy and for Rituxan in the multiple indications for which it was subsequently approved.
Commentary
Dr. Nye
Today, almost a quarter of a century later, targeted monoclonal antibodies as well as small molecules are standard therapy, extending overall survival for many cancer survivors. At Cancer Biomarkers Conference IV in October, researchers from most of the major academic centers in the United States presented the latest findings in biomarkers and advances in targeted therapy. Many of the presentations focused on targeted therapy, using small-molecule tyrosine kinase inhibitors, immunotherapy by means of treatment with the checkpoint inhibitors PD-1 and PD-L1 monoclonal antibodies, and drugs that target the genetic abnormalities ALK, EGFR, BRAF, ROS1, and, most recently, NTRK. It was evident from discussions with the audience of pathologists, oncologists, and patient advocates that our understanding of disease mechanisms and associated biomarkers is advancing at an exponential pace that is making it difficult for the oncology community to keep up.
Although some patients are benefiting from these new discoveries, many challenges remain, as with the introduction of Rituxan. How do we make sure every patient receives biomarker testing and the appropriate first-line and subsequent therapy? Is there a way to predict which patients are likely to have severe and possibly fatal side effects from immunotherapy, and how can we mitigate the side effects? Should we perform next-generation sequencing on every patient to better understand the treatment options when a patient relapses on a specific targeted therapy?
In the late 1990s, Genentech funded the National Coalition for Cancer Survivorship’s development of the Cancer Survival Toolbox, a unique self-advocacy program for cancer survivors. We have worked on this program for more than 20 years, and over the years almost every major pharma company has supported its production and distribution. That the Cancer Survival Toolbox has been accessed by more than a million cancer survivors and is still available today is evidence of the importance of self-advocacy.
At the boot camp that preceded the biomarkers conference, the continuing need for education and patient advocacy was made clear in the moving story told to us by a young woman who has two young children. She is a nonsmoker who after several months of severe illness was diagnosed with non-small cell lung cancer. Once diagnosed, her oncologist was so concerned about her failing health that he wanted to start chemotherapy immediately, but her husband, who is not a medical professional, searched the Internet for information and made sure that her health care team tested her biomarker profile. Fortunately, she is with us today in good health because the tests revealed that her tumor was positive for ALK and she was able to receive targeted therapy. Every cancer patient needs an advocate, even those of us familiar with oncology, because a cancer diagnosis is scary and it’s hard to find the right information and make the right decisions under stress.
Conference keynote speaker John C. Ruckdeschel, MD, a University of Mississippi Medical Center oncologist, reviewed the proliferation of tumor markers that can identify actionable mutations. The guidelines (CAP/IASLC/AMP) are inevitably lagging behind the pace of research developments. For example, standard panels of single-gene tests—EGFR, ALK, ROS1, and others such as BRAF—are proving to be insufficient to diagnose and successfully treat all NSCLC. Dr. Ruckdeschel and other speakers insisted that NGS has to be embraced in order for the best available treatment to be selected, particularly for tumors amenable to immune therapy. Reflex testing, even though performed in accordance with guidelines and standard practice, is proving inadequate in many cases.
Single-gene assays are well established, the data are easier to report and interpret, and the assays are less costly than NGS. Therefore, the NGS approach has to be justified by the requester and, in particular, how extensive the NGS testing (sequence limitation) is to be for a particular case. However, selecting the wrong treatment by failing to identify the chief tumor driver causes a delay in implementing the optimum treatment and may introduce complications. For example, the incidence of the rare but serious complication of interstitial pneumonitis following immune checkpoint inhibition therapy varies with tumor type. Also, recently published data suggest that patients treated with immune checkpoint inhibitors who are concomitantly or sequentially treated with TKIs are at greater risk for developing pneumonitis.
As was clear from the presentation on regulation and billing for molecular testing by Timothy C. Allen, MD, JD, professor and chair of the Department of Pathology at the University of Mississippi Medical Center, the new paradigm for cancer therapy is not only presenting major challenges for diagnostic and treatment guidelines but also revealing serious deficiencies in current health care regulations, systems, and procedures for reimbursement. Failure to conform to current treatment guidelines and up-to-date standards of care exposes the medical practitioner to potential tort litigation for negligence or malpractice.
All of which contributes to a growing need for rapid and effective communication between pathologists, oncologists, and patients. Pathology is the foundation for targeted therapy and patient-centered care in oncology. As Dr. Allen wrote recently in The Pathologist, it is important for pathologists to become better communicators to meet new responsibilities as more engaged medical team players, advocating for adoption of new biomarker tests and supporting oncologists in delivering optimal outcomes for patients. As the late Ellen Stovall of the National Coalition for Cancer Survivorship said often, our vision is “to transform each and every person’s experience of living with, through, and beyond the diagnosis of cancer.”
Dr. Nye, whose doctoral degree is in immunology, began her career developing immunodiagnostic tests in London, England. She and her team at Medical Minds specialize in physician and patient education and have developed medical communications in almost every disease category, including oncology diagnostics and therapeutics, during the past 25 years. She led the launch of Rituxan at the BioGenesis Group/Torre Lazur, the agency of record. She is a cancer survivor.