ASCO Update: Personalized Cancer Care – Our Contributions

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As part of our ongoing blog postings we like to include recent presentations and publications. On July 9, I described our ASCO presentation exploring crizotinib, “Functional Profiling Leads to Identification of Accurate Genomic Findings.

To conclude the review of our other presentations from that meeting, here is a brief summary of our work.

The first of the two was our international collaboration in personalized medicine for the treatment of advanced and drug-refractory cancers: “Clinical application of human tumor primary culture analyses.” The study reviewed the results of 67 patients from institutions across Brazil.

Tumor samples were transported by overnight courier to California for drug response profiling. A broad array of tumors were included. The overall success rate provided actionable results in 62 of 67 patients (92 percent). More than 75 percent of the studies provided results for between 8 and 16 drugs and combinations with a median of 12 reported. Several strikingly good responses were observed, including novel combinations identified in the laboratory. This study confirms the feasibility of international collaboration and reflects the globalization of medical care delivery.

The final study published by ASCO was also a collaborative effort with SageMedic of Larkspur, CA, The Ludwig Maximilians University Munich, Germany and the Weisenthal Cancer Group. The study was a meta-analyses that examined the sensitivity and specificity of human tumor primary culture studies and the efficacy of drug therapies selected, based on laboratory findings. In aggregate there were 28 retrospective and 15 prospective trials included.

The overall sensitivity was 0.92 (95 percent C.I. 0.89 – 0.95), and specificity of 0.72 (95 percent C.I. 0.67 – 0.77) with an area under the curve for the ROC of 0.893 (SE = 0.023, p < 0.001). When clinical outcomes were examined, it revealed a two-fold improvement for assay-guided therapy for standard of care (odds ratio 2.04, 95 percent C.I. 1.62 – 2.57, p <  0.001). Finally, the one-year survival rate for assay-guided therapy proved superior (OR 1.44, 95% C.I. 1.06 – 1.95, p= 0.02).

As can be seen from this well conducted meta-analysis, there is a wealth of evidence to support the use of human tumor primary cultures for the selection of chemotherapy.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

2 Responses to ASCO Update: Personalized Cancer Care – Our Contributions

  1. Phil says:

    My son is Stage 4 ALK and was positive in FISH analysis. Crizotinib is working well but I want to know about resistance, brain mets, immunotherapy, and the most appropriate 2nd line drug or combo. Is the value of cytometric testing mostly moot now that we already know ALK+? I suspect there still is value to be captured and I want to know what it is. Thanks.

    • My presumption is that this is a Stage IV Non-small cell lung cancer. Alk gene rearrangements are found in 4 or 5% of patients and do respond very nicely to Crizotinib. Progression in the brain or other sites can occur and the drug generally provides responses measured in months up to one or more years. If progression is observed, we recommend consideration of one of the second generation ALK inhibitors of which there are several. Dr. Ou at UC Irvine, and Dr. Camidge at U of Colorado and other centers are engaged in Phase II studies of these small molecules.

      If these do not provide effective treatment, then options include chemotherapy or newer forms of immune therapy of which anti-PD1 and anti-PDL1 are options. If chemotherapy is to be considered, we could be very helpful in examining the options as well as exploring some of the newer small molecule inhibitors.

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