Maurie Markman, MD
Editor-in-Chief of OncologyLive
Senior vice president for Clinical Affairs and National Director for Medical Oncology
Cancer Treatment Centers of America, Eastern Regional Medical Center
It is widely recognized that the paradigm associated with the management of the individual patient with cancer is undergoing major, even truly revolutionary changes. The days when only the results of randomized phase III trials informed rational decision making and all patients with a given tumor type are treated with an identical antineoplastic drug regimen are rapidly coming to a close.
Increasingly solid data reveal the clinical relevance of treatment approaches based on unique molecular targets present within the tumors of individual patients. For example, it is known today that the presence of HER2 overexpression is relevant in several tumor types where the administration of a HER2 inhibitor will favorably impact outcome, and documentation of a BRCA
mutation will define the patient population most likely to benefit from the delivery of PARP inhibitors (when at least one agent in this important class of drugs finally receives long-overdue regulatory approval).
Further, it is reasonable to anticipate that in the near future knowledge of unique normal polymorphisms present within the genetic makeup of individual patients will become highly clinically relevant in helping to reduce the risk of particular serious treatment-related toxicities, and will also be shown to impact cancer-related survival outcomes. Such information may substantially influence decisions related to the delivery of specific therapies.
Unfortunately, the sheer magnitude of the molecular data that clinicians will need to consider and the speed at which additional potentially highly actionable information is becoming available is simply staggering. How can a conscientious but very busy practitioner keep up with the massive quantity of data?
Consider, for instance the individual tumor-specific information being made available through an ever-increasing variety of molecular CLIA-certified testing services? Although these often quite detailed reports prepared for clinical use may be highly informative and well structured, the most important question from an oncologist receiving such a report is likely to be: How does the specific data provided in this report help me to select the best therapeutic approach/option for my patient?
Panel Includes Genomic Experts
A molecular tumor board is an increasingly popular and relevant concept designed to assist that inquiring clinician in precisely this situation. Like any other tumor board, the management of individual cases is discussed by a team of relevant specialists (ie, medical, surgical, radiation oncologists; pathologists; radiologists, etc), but in this setting the specific focus will be on the use of the data obtained from a genomic/molecular analysis (including tumor and germline abnormalities or normal polymorphisms) and how this knowledge can be optimally utilized to favorably influence outcomes. As a result, members of the group would include not only clinicians who routinely participate in traditional tumor boards, but also individuals with both a specific interest and expertise in the clinical evaluation of the molecular profiling.
An example of the basic organization of, and preliminary success with, a molecular tumor board was recently reported by a team at the Moores Cancer Center at the University of California, San Diego.1
As previously noted, this center’s tumor board was composed of individuals with both laboratory and clinical experience with such testing. A major goal of this specific effort was to provide a clinically relevant interpretation of reported molecular results obtained from the cancers of individual patients that would lead to the subsequent selection of an optimal management approach and hopefully a favorable clinical outcome.
Molecular Challenges in Moores Tumor Board Study1
Cases: 34 patients
Tumor types: 8
Molecular aberrations — defined as mutation, rearrangement, deletion, amplification, or insertion
Median 4 aberrations per patient (range, 1-14 abnormalities)
No 2 patients had identical abnormalities
74 genes with 123 distinct aberrations
107 distinct abnormalities seen only once
Highest rate of abnormalities in TP53, MYC, and PIK3CA genes
In this report, a total of 34 patients were discussed at the tumor board beginning in December 2012. Notably, these patients had previously been rather heavily pretreated (median of three prior therapeutic regimens) and their cancers were found to possess a number of molecular abnormalities (median four per tumor). These data emphasize the difficulty associated with attempting to define an objectively reasonable future therapeutic strategy in the presence of a multiple potential targets in patients with limited known therapeutic options.