Genome-Based Diagnostics Demonstrating Clinical Utility in Oncology: Workshop Summary (2013) / Chapter Skim
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5 Advancing Molecular Diagnostics for Oncology
5 Advancing Molecular Diagnostics for Oncology
Pages 51-68
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From page 51... ...
Each of the five speakers emphasized that partnerships are an especially valuable way to accelerate evidence development. The availability of specimens and good quality clinical data, to name just one example, inevitably requires collaborative efforts among stakeholders.
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It also has a leukemia tissue bank that has collected frozen leukemia specimens and a lung cancer tissue bank that has collected frozen lung cancer specimens. All of the specimens, with the exception of those in the lung cancer bank, have been collected only from patients enrolled in clinical trials.
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A breast cancer study done in the 1990s established that Taxol is a useful component of adjuvant chemotherapy in women with node-positive breast cancer (Henderson et al., 2003)
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With regard to prospective marker validation studies, Schilsky mentioned a "perfectly designed biomarker study that fell flat on its face." A collaboration among several cooperative groups sought to validate the utility of fluorescence in situ hybridization (FISH) testing to select patients to receive erlotinib as part of their therapy for non-small-cell lung cancer.
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Therefore, the most important step to improve the generation of evidence for molecular diagnostics in oncology, according to Schilsky, is to determine what unmet medical needs require prospective randomized trials to develop the evidence base. Schilsky also noted, as did other people at the workshop, that most adult patients with cancer are not part of clinical trials.
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Wayne Calloway Chair in Urologic Oncology and chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, described the Prostate Cancer Clinical Trials Consortium (PCCTC)
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Food and Drug Administration; OBRR, FDA Office of Blood Research and Review; PCCTC, Prostate Cancer Clinical Trials Consortium. SOURCE: Howard Scher, workshop presentation, May 24, 2012.
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The objective is to establish a "Rosetta stone" resource of mutation profiles of advanced prostate cancer for researchers and patients. This effort will establish advanced prostate cancer as a model tumor type for the precision medicine paradigm and facilitate the use of clinical sequencing for cancer management, Scher said.
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• Identifying rare "actionable" mutations in advanced prostate can cer and providing rational clinical trial options to patients. The key to success, said Scher, will be the availability of analytically valid assays when the trials are ready to begin.
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Novel Partnership Strategies to Develop EVIDENCE OF Clinical Utility As Gabriela Lavezzari, director of development and diagnostics at Express Scripts, observed, the drug development pipeline is full of therapies accompanied by biomarkers (see Figure 5-3)
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Trastuzumab- Iniparib Bapineuzumab CFTR G551D emtansine BRCA ApoE4 Ridaforolimus HER2 Dacomitinib Pacritinib HER2 / EGFR Afatinib KRAS JAK2 V617F Pertuzumab EGFR CO-101 AEZS-108 HER2 mutations hENT1 LHRH receptor+ Tafamidis Ponatinib Elacytarabine Solanezumab V30M TTR mutation BCR-ABL hENT1 Amyloid beta variations Bosutinib T315I Darapladib Neratinib BCR-ABL Lp-PLA2 HER2 Mipomersen Midostaurin Rindopepimut ApoB-100 FLT3 receptor EGFRvIII Omacetaxine Dalcetrapib BCR-ABL CETP mutations Migalastat Alpha-Gal A mutations FIGURE 5-3 Many drugs with potential companion tests are in the development pipeline. NOTE: APO, apolipoprotein; BCR-ABL, breakpoint cluster region-abelson; BRCA, breast cancer susceptibility gene; CETP, 5-3 Figure cholesteryl ester transfer protein; CFTR, cystic fibrosis transmembrane conductance regulator; EGFR, epidermal growth factor receptor; FLT3, fms-related tyrosine kinase 3; Gal, galactosidase; hENT1, human solute carrier family 29 (nucleoside transporters)
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From page 62... ...
The payer, the physician, and the patient that ultimately has to take the medication all have to work together." Assessing Clinical Utility with Real-World Evidence Major changes in the development of drugs and companion diagnostics have been forcing pharmaceutical companies to adopt new models, said Greg Rossi, vice president, Payer and Real World Evidence, at AstraZeneca UK. Information about disease is rapidly increasing, providing more potential therapeutic targets and identification of biomarkers.
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There is a contract with patients to make sure that the appropriately rigorous methodology and analysis are being performed in clinical trials to ensure that benefits are being maximized. There is also a need to team up at various stages with academic researchers, companies, regulatory agencies, payers, and health care systems in order to make sure that the right type of evidence is being generated.
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The ACCE model process has defined clinical utility as "the balance of benefits and harms associated with the use of a test in practice, including improvement in relevant outcomes and the usefulness of added value in decision making compared with not using the test."3 Observational studies should suffice to achieve this outcome, Rossi said, but in cancer, separating the clinical difference from the noise of the assay remains very difficult. Studies of electronic medical records and claims databases could be useful in determinations of clinical utility, but these are currently hampered by such challenges as a lack of integrated data on important patient clinical characteristics, a lack of pathologic and diagnostic data, and difficulty collating all associated direct and consequential costs.
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All the stakeholders have recognized their roles in the process and are trying to clarify what their needs are for demonstrating clinical utility. Speakers made a number of recommendations (see Box 5-1)
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• tudies of clinical utility should be conducted in settings that are relevant S to more real-world clinical decisions. (Freedman)
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• biomarker study registry could aid in identifying relevant biomarker stud A ies for overviews and meta-analyses, make study protocols available, and help reduce nonpublication bias and selective reporting. (McShane)
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• more relevant term than "clinical utility" for most patients is "personal A utility" or "personal guidance." (Collyar) • atients need to get test results quickly and in clear language, and test P results need to be updated as the test or a person's condition changes.
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