Chicago, IL—“Precision medicine” is the new catch phrase in oncology, and examples of it were evident across the vast halls of McCormick Place at the 2012 American Society of Clinical Oncology (ASCO) meeting.
Precision medicine is the next iteration of “personalized medicine,” a moniker perhaps meant to convey the increasing refinement of the molecular targets that underlie tumors. It has become evident that mutations that describe certain tumors—such as the epidermal growth factor receptor (EGFR) mutation in non–small-cell lung cancer (NSCLC)—may be present to some extent in a variety of apparently unrelated cancers. This means that drugs targeted to one tumor type may be useful in small subsets of other types of cancers. This has implications for drug development, clinical trials, and the treatment of patients.
“We now understand that it’s not sufficient to identify a tumor based on the histology or the organ of origin, as we did traditionally, but rather that tumors are heterogeneous. We need to understand the particular molecular driver of the tumor to select appropriate therapy,” said ASCO outgoing president Michael P. Link, MD, during a press briefing.
As medicine has become “president” in recent years, molecular profiling of the patient has become a standard practice, at least for many tumors and in academic centers. But this is an expensive process, and sessions at ASCO 2012 were devoted to best practices in this area, at least for lung cancer, colorectal cancer, and neuro-oncology.
In some instances, molecular profiling may be life-saving, said Nicholas J. Vogelzang, MD, Chair of ASCO’s Cancer Communications Committee and Chair and Medical Director, US Oncology Research, Houston, TX, and an oncologist at Comprehensive Cancer Centers of Nevada, Las Vegas. Dr Vogelzang pointed out that it is no longer uncommon for patients with disease refractory to established treatments to go hunting for unsuspected mutations that might be targeted by drugs that would otherwise never be considered. “It’s not intuitive,” he said. “Unusual tumors have these mutations, so you have to test them.”
Drugs that Are “Crossing Over”
For several drugs that were considered breakthroughs in one tumor type, treatment niches are emerging in other cancers. A striking example is crizotinib, the ALK inhibitor that elicits robust responses (70%-80%) in the 5% of patients with NSCLC who have ALK gene abnormalities. Investigators reported at ASCO that crizotinib is also an active treatment for a phenotypically unrelated set of aggressive pediatric cancers.
In a phase 1 study of 70 children, treatment with crizotinib led to complete responses in 88% of patients with anaplastic large-cell lymphoma and produced complete and partial responses in patients with other tumor types as well. Many of these young patients have maintained their responses to crizotinib for more than 2 years, reported Yael P. Mossé, MD, Assistant Professor, Perelman School of Medicine at the University of Pennsylvania, and an attending physician at the Children’s Hospital of Philadelphia.
“It’s remarkable that this targeted oral medication provided such a substantial benefit in these children with highly aggressive cancers, most of whom had already undergone every available therapy,” Dr Mossé said.
Dr Vogelzang, who commented on the results, said he had also witnessed a dramatic response to crizotinib in an adult with ALK-positive anaplastic large-cell lymphoma. “The patient was very, very ill. She achieved a complete response with crizotinib and was able to receive a transplant. So, this drug does have dramatic potential in older patients as well, and in patients with other tumors.”
BRAF inhibitors may also have crossover appeal, because colorectal and lung cancers also harbor BRAF mutations.
A “Blueprint” for Change
In keeping with the rapidly emerging molecular landscape, ASCO is pushing for an accompanying paradigm shift in cancer research and drug development. In November 2011, ASCO issued a report that lays out its vision for transforming clinical and translational research to deliver more effective and personalized cancer therapies faster.
“Advances in cancer prevention, detection, and treatment have already extended the lives of millions of adults and children living with cancer—but the critical question is, ‘Where do we go from here?’” said Dr Link. “This report aims to set us on a path to deliver the new therapies that patients urgently need.”