Precision Therapeutics Can Pave the Path to Curing Cancer
Surabhi Dangi-Garimella, PhD
“What are we paying for when we pay for cancer care, and how do we do so sustainably?” was the question Joseph Alvarnas, MD, asked the audience at the 4th annual meeting of Patient-Centered Oncology Care. Alvarnas is the director of value-based analytics at City of Hope, Duarte, California, and also serves as editor-in-chief of Evidence-Based Oncology.
The question is important, especially as we move towards higher cure rates, innovative technologies, and services— the reimbursement structure needs to be dynamic, he thinks, to accommodate today’s rapid changes in medicine. Alvarnas believes that the development of targeted immunotherapy agents has had a profound impact on patient outcomes and has brought “cure” into the picture.
Presenting data that painted an upbeat picture of cancer cure rates, he said, “As of January 2014, there were 14.5 million cancer survivors,” adding that analysis of the Surveillance, Epidemiology, and End Results program registry, between 2005 and 2011, saw the highest level, ever, of cancer survivorship across various cancer types, much of which he attributes to our greater understanding of the disease through genomic and proteomic advances. However, for some patients with advanced, refractory cancers, a cure might only be in the distant future.
HEMATOLOGICAL MALIGNANCIES AND PRECISION MEDICINE
Alvarnas then dug deeper, and provided a historic perspective of the field’s understanding of blood-based cancers. Using acute lymphoblastic leukemia (ALL) as an example, he said, “It’s only by moving forward from an early paradigm to a much more mature one, based upon understanding of the biology of cancer, that we’ve moved on.”
The discovery of mustard gas during World War I led to the development of alkylating agents as chemotherapy, and in combination with surgery and radiation therapy, the 3 modalities are still used in the clinic today, said Alvarnas. Explaining the importance of the discovery of the Philadelphia chromosome—which led to the development of the tyrosine kinase inhibitors (TKIs)—and the use of fluorescence in-situ hybridization or FISH technology to accurately detect low levels of residual disease, Alvarnas said that the 2 developments, together, have resulted in complete hematological and molecular remissions. He believes TKIs “turned this disease into a chronic illness like diabetes, rather than to something that we would normally think as being an imminently devastating disease.”
Precision medicine has radically altered the treatment landscape, according to Alvarnas; whether it be precision in diagnosis, guided by molecular diagnostic tests, or precision in treatment, with the various targeted therapeutics. The next step, he said, is “to fully leverage the information in therapeutic decision making.”
“So these advances lead to more effective risk stratification and as we move towards discussions of payment, I don’t think you could have a meaningful discussion of payment unless you include risk,” said Alvarnas. He then went on to describe the disconnect that emerges with the International Classification of Diseases, or ICD codes, falling way short of being able to capture the nuances of the various therapeutic classes.
Alvarnas then shared a variety of genomic cluster maps of ALL patients of different age groups. “This gives you a sense of how chromosomes inform risk, and subsequently risk informs therapeutics,” he said. Genome arrays, he explained, can provide significantly more detailed information on the genetic and genomic differences between different cancers, than would a microscopic slide with a tissue section. “Each one of these should be treated in a way that respects the molecular biology. These are the insights that are leading towards cancer cures.”
“So, the profound evolution in the therapeutic approach is that surgery, chemotherapy, and radiation therapy have in many ways been supplanted, and often replaced, by biological and targeted therapeutic technologies,” including the TKIs, such as Bruton’s tyrosine kinase inhibitors for chronic lymphocytic leukemia and non-Hodgkin lymphoma, immunomodulatory drugs or IMiDs and proteasomal inhibitors for myeloma and non-Hodgkin lymphoma, and ruxolitinib for myeloproliferative disorders.
THE NEXT FRONTIER: IMMUNOTHERAPEUTICS
“Harnessing the power of the immune system is becoming increasingly powerful in terms of its role in investigation and also translating into real therapeutics,” Alvaranas explained, adding that nonoverlapping toxicities with traditional chemotherapy, the ability to specifically target tumor cells, and the lasting memory of the immune system are all significant advantages of this new direction in cancer care.
The armamentarium of immune-based therapies include monoclonal antibodies, monoclonal antibody–drug conjugates, and T-cell based therapeutics, such as the chimeric antigen receptor T cells, or CAR-T cells.
Narrating the profound influence of immunotherapy on patients with ALL, Alvarnas explained that, blinatumomab (used to treat ALL patients who express the CD19 receptor), helps bridge a patient—who would otherwise have died of his disease—to undergo transplant and subsequent cure. “And, again, the complete responses are quite extraordinarily high with 80% of patients treated with this agent achieving a molecular complete response.” He also projected that CAR-T cells, which are currently being evaluated in phase 2 trials, would be an important addition to the cancer armamentarium.
“I think for the first time we have the tools necessary to find cures for many of our patients. For much of the duration of the war on cancer, we were unable to ask the right questions. We’re now poised, through advances in technology, to ask the right scientific questions that, in fact, can translate through research to the cures that can really change this equation for patients broadly,” said Alvarnas.
“For all of us who have had those uncomfortable discussions with patients in that we’ve not been able to offer meaningful therapy, we’re having those conversations less frequently. I think we’re better able to inform our conversations with a biological understanding, sometimes on a molecular level, of the diseases we treat and better match our patients to the therapeutic armamentarium that’s available. And I look upon this with extraordinary hope,” he concluded.