John L. Marshall, MD
Cancer care is shifting from a consumption to a value-based model, and precision oncology should play a vital role in that process by helping to deliver more effective therapies with more manageable pricing profiles, according to an internationally prominent leader in the colon and gastrointestinal (GI) cancer fields.
John L. Marshall, MD, chief of the Division of Hematology/Oncology at Georgetown University Hospital, described a broad vision for developing new therapies and providing improved care as part of a value-based equation in an opening address at the 1st Annual School of Gastrointestinal Oncology™ that Physicians’ Education Resource (PER) hosted in New York City on April 23.
Marshall, who co-chaired the meeting, said medical centers are marketing precision medicine oncology offerings but they are not truly practicing it. “Nobody really is,” he said. “We have a few bits and pieces.”
“To move the bar, we have to get away from trial-and-error empirical medicine and we have to embrace the idea that cancers are complex and different, and begin using this concept of precision medicine,” Marshall said.
Prevalence of GI Cancers
In putting the need for change into context, Marshall struck a note of urgency. He said GI cancers collectively are the most common and most fatal malignancies worldwide and constitute “a major health problem.”
He said the worldwide incidence and mortality rates from GI cancers are projected to rise from nearly 4 million cases and less than 3 million deaths in 2008 to more than 6 million cases and more than 4 million deaths by 2030.1,2 These projections include statistics for cancers of the pancreas, liver, esophagus, and stomach, as well as colorectal cancer.
However, just as patients in the United States struggle with the costs of cancer care, people throughout the world are in worse straits. Marshall said only about 1 in 7 people worldwide has access to cancer care.
“Cancer care is a luxury item—it requires multidisciplinary care, it requires pathology, MRI scanners, CyberKnives—we need a proton beam center,” he said. “We need high-tech surgery, we need drugs, we need supportive care.”
Molecular Testing in GI Cancers
Although researchers and clinicians have made progress against GI cancers, Marshall said fundamental changes are needed in the process for testing molecularly targeted therapies in clinical trials and in approaches to treating patients in daily practice.
“Over 95% of the patients today are treated on pathway, on guidelines,” said Marshall. “That’s good, but that also means those patients are not contributing to the future. They’re getting today’s standard, and so we’re accepting today’s standard as an OK place to be.”
Using colon cancer as an example, Marshall said there are no clear answers as to why therapies that help patients with metastatic disease do not work well in adjuvant settings. “I think these are actually different biologic diseases,” he said, referring to stage III and IV cancers. “We’ve begun to reshape our thinking about colorectal cancer.”
Notably, he said that the clinical utility of microsatellite instability (MSI) status was correlated with patient responses to fluorouracil-based adjuvant chemotherapy for patients with stage II or III colon cancer in 2003, but that it took more than a decade to become more widely integrated in clinical practice.3
As it stands now, molecular testing in colorectal cancer consists of determining whether a tumor sample contains mutations in RAS family (KRAS or NRAS); BRAF mutation testing if the tumor is RAS wild-type; and MSI, a molecular signature commonly caused by the loss of DNA mismatch-repair function.3
Several gene profiling assays also are commercially available but these are helpful for classifying patients into risk levels and do not help clinicians sort out which patients would benefit from chemotherapy and which patients would not, Marshall said.
Looking forward, Marshall believes the future lies in broad molecular tumor profiling, which offers the potential to analyze patients individually on a more detailed level. For instance, Marshall said that clinicians could determine not only which cell-signaling pathway was activated in a given cancer, but also which components of that circuit were operative for a particular patient.
“It’s this level of granularity that we may need to get to in order to really understand precision medicine,” he said.