Making Personalized Cancer Care Routine
A small group of oncologists and pathologists from five medical centers gathered last fall to talk about the nuts and bolts of personalizing cancer care. On the table were a host of practical issues related to one big question: Can hospitals routinely use genetic and molecular information from tumors to match patients with the most appropriate drugs in an affordable and timely manner?
The answer to this question may not come for years. But some lessons about what works and what doesn’t could emerge much sooner. Massachusetts General Hospital and Memorial Sloan-Kettering Cancer Center (MSKCC) have begun to screen all lung tumors for genetic changes that could reveal whether a particular treatment is likely to work or should be avoided.
“We believe the profiling of tumors will become more and more integrated with clinical practice in the future, and we want to see that happen sooner rather than later,” said Dr. Leif Ellisen, an oncologist at Mass General and co-director of a new molecular pathology lab that profiles the tumors. “Most centers realize that this is where the field of oncology is going in terms of directed therapies.”
He noted that interest in tumor profiling extends well beyond the centers that met last fall (which also included Dana-Farber Cancer Institute, University of Texas M.D. Anderson Cancer Center, and Vanderbilt Medical Center). In fact, personalizing cancer care is the theme of the American Society of Clinical Oncology (ASCO) Annual Meeting this week in Orlando.
At this stage, however, the approach has some important limitations. For starters, only a fraction of the molecular changes involved in cancer have been identified, and more drugs that target these changes are needed. At MSKCC, nearly half the lung tumors tested do not harbor one of the known gene mutations associated with the disease.
Lung Cancer: A Test Case
Despite the limitations, the current understanding of lung cancer is vastly different from a decade ago, when most tumors were thought to be essentially the same and patients received the same drugs. Today, it’s clear that subsets of tumors are driven by gene mutations that activate cancer-promoting signals in cells and, in some cases, drugs are available to block these signals.
“We’re nearing a point where patients need not only a diagnosis of lung cancer but also to know the molecular subtype of the tumor,” said Dr. Lecia Sequist, who treats patients with lung cancer at Massachusetts General Hospital Cancer Center.
Mutations in the gene EGFR, for instance, tend to make tumors respond to gefitinib (Iressa) or erlotinib (Tarceva). These drugs are pills, taken once a day, that block critical signals in tumors and usually have fewer side effects than chemotherapy. While less than 30 percent of lung cancers in the United States carry the mutations, those that do have a 70 percent chance of responding to the drugs.
The Mass General test profiles 13 genes, including EGFR, that are altered in a variety of cancers. A team led by pathologist Dr. John Iafrate developed a process for automatically extracting DNA from standard tumor specimens and screening the DNA for 120 cancer-related changes. The pathology lab tests about 20 lung tumors per week, a number that will rise as the program is gradually expanded to include all cancer patients.
By making the test broad rather than focused on a single cancer, the researchers hope to pick up mutations that may be rare in one tumor type, but for which a treatment already exists. Some lung tumors have alterations in the gene HER2, for example, and these tumors may respond to the breast cancer drug trastuzumab (Herceptin).
“In our view,” said Dr. Ellisen, “medicine isn’t personalized if you’re only testing patients for the common mutations.”
A shift toward personalized care may be happening now because of technologies that can test for multiple genetic changes simultaneously, and also because of growing evidence that patients benefit. For instance, many colorectal cancer patients undergo gene testing before starting on cetuximab (Erbitux) to determine whether they are candidates for the treatment or should be spared the costs and side effects.
“This approach is exactly what the patients want,” said Dr. Mark Kris, chief of the Thoracic Oncology Service at MSKCC. “They want to know that we’ve used all of our resources to analyze their cancers. It’s what clinicians want as well—to give patients treatments that are targeted to their particular disease.”
Interim results from the IPASS lung cancer trial, presented at the ASCO meeting, underscored the need for tumor testing. The randomized trial compared gefitinib and chemotherapy as a first-line therapy and found that patients with EGFR gene mutations tended to respond better to gefitinib. Other patients fared better with chemotherapy.
The study is relevant to personalized medicine because nearly all the participants fit the profile of someone who may benefit from gefitinib or erlotinib. That is, they were Asian nonsmokers or light smokers. Yet only some of these individuals—those with EGFR mutations—actually benefited from gefitinib.
This finding, Dr. Sequist noted, suggests that patients may need to have their genes tested rather than simply relying on doctors to make an educated guess about who will benefit most from these drugs.
The need to collect tissue samples from patients for testing and the fact that many tumors eventually develop resistance to targeted drugs are among the many challenges facing the new field. Another complication, the researchers said, is that patents on gene mutations in the future could narrow the scope of testing at some institutions.
Nonetheless, valuable lessons may come from the current programs, including how to make personalized cancer care work within the current health care system. The investigators have been sharing their experiences with colleagues, and later this year they plan to publish a summary of the meeting last fall.
“Doing this within the current health care system is unbelievably complicated,” said Dr. Kris. “This is not how hospitals work right now, and it is not how oncology is practiced.” The investigators need to both “work out the bugs” in the current systems and demonstrate the benefits of this approach to the medical establishment, he added.
“It’s not easy,” Dr. Kris continued, “but we and the other institutions doing this are all committed to taking this forward and making it the standard of care.”
—Edward R. Winstead