Kellie Carey’s doctor finally stopped dodging questions about how long she had to live six weeks after he diagnosed her lung cancer.
“Maybe three months,” he told her in his office one sunny May morning in 2010, she recalls.
Yet she is still alive, a testament to the most extraordinary decade of progress ever in the long scientific struggle against lung cancer.
Tests found Ms. Carey’s lung cancer to be of a rare type that researchers had found just three years earlier by deciphering its genetic code. The 45-year-old businesswoman in 2010 went on a drug Pfizer Inc. PFE -0.79% was testing for that type. By pinpointing her cancer, the drug probably helped give her years more to live than chemotherapy would have, her doctors say.
Kellie Carey, who was given three months to live in 2010, discusses her lung-cancer treatment with her doctor, Roy Herbst, last month.
That is remarkable because lung cancer for decades defied efforts to find drugs that could extend an average patient’s life by even a few weeks.
But an explosion in knowledge about the genetic mutations that cause tumors is just now offering the first real promise of drugs that can control what is the most-common and most-deadly cancer.
Ms. Carey has one of at least 15 lung-cancer variations, almost all of which scientists didn’t know existed 10 years ago. Researchers have identified those variations, most of them in just the past four years, by decoding DNA in tumors—akin to how crime labs analyze DNA to genetically fingerprint suspects.
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Q&A: How Do Targeted Cancer Therapies Work?
The newfound variants have led major cancer centers to revamp their approach to treating cancer and have spurred a rush among drug companies to find medicines that narrowly target each one.
The drugs don’t cure cancer and face significant hurdles. But doctors now talk of a “precision medicine” approach in which those pinpoint drugs can treat tumors far more effectively than catchall chemotherapy.
“What we’re seeing is the beginning of a revolution in therapeutics,” says Janet Woodcock, director of the Food and Drug Administration’s Center for Drug Evaluation and Research. “We can only hope that this gets us to where cancer is managed or curable.”
Among signs that revolution really is afoot: A June 2013 study found that lung-cancer patients who were treated with drugs targeted at their genetically identified varieties lived 1.4 years longer than patients on chemotherapy whose cancers weren’t genetically identified.
In effect, lung cancer is no longer a few common diagnoses. Instead, it is a growing list of rare cancers, each a target for its own drug regimen.
“It’s likely that more than half of tumors have some alteration we can target with a drug,” says John V. Heymach, a lung-cancer specialist at MD Anderson Cancer Center, Houston. “They may not all have the same success, but we know that in many cases, a targeted agent will work very well.”
The same goes for other malignancies: Scientists have decoded tumor DNA from breast, colon, kidney, skin and other cancers in recent years to discover scores of variations they didn’t know existed before.
Research hospitals like MD Anderson, Vanderbilt University and Massachusetts General Hospital are among a growing number of cancer practices that routinely decode the tumor DNA of most patients with advanced cancer.
The lists of newfound variations have invigorated the drug industry, with companies like Pfizer, Roche Holding AG ROG.VX -1.49% and Merck MRK -1.24% & Co. racing to develop drugs that target each one.
Last year, nearly 1,000 cancer drugs were in clinical development, up 52% from 2006, says the Pharmaceutical Research and Manufacturers of America, a trade group. The “vast majority” of that growth is from drugs targeted at genetic mutations, says Bill Chin, the group’s head of science and regulatory affairs.
Three drugs are on the market for newly discovered lung-cancer mutations. Dozens more are in clinical trials. Some approved for other cancers appear effective for specific lung cancers. And drug companies are targeting other mutations of all cancer types.
At least half the 27 medicines on Novartis AG’s NOVN.VX -1.16% current list of oncology drugs in clinical development target cancer mutations. Precision medicine is “fundamentally changing the way we think about cancer drug development,” says Hervé Hoppenot, president of the company’s Novartis Oncology unit.
Just last year, the FDA established a “breakthrough therapy designation” to hasten approval of experimental drugs that show striking benefits in early trials, including those targeted at cancer mutations.
Ms. Carey’s diagnosis in 2010 came just as that thinking was starting to change. Her roller-coaster ride of cancer remission and recurrence over the next three years shows the promise and shortcomings of precision medicine.
Ms. Carey, who worked for a business selling private jets, suffered an apparent seizure at her gym. Doctors discovered a nodule in her lung of cancer that had spread to her brain. Surgery and radiation treated the brain tumor.
But when the New York City resident’s doctor said she probably had three months left, “I definitely felt like there were no options,” she says.
It wasn’t an unusual prognosis for lung cancer in 2010. Three decades of research starting in the 1970s into hundreds of potential lung-cancer drugs had produced dismal results, says MD Anderson’s Dr. Heymach: Over that time, a lung-cancer patient’s median survival improved by just one month, to eight months.
Ms. Carey found hope in news accounts of a drug Pfizer was testing against a cancer type researchers had identified in 2007. The type was caused by a mutation in the so-called ALK gene—it normally plays a role in brain development—and Ms. Carey wanted to know if that was her cancer.
In 2010, precision medicine was still so nascent that Ms. Carey had to show unusual persistence. Few doctors even considered testing tumors for mutations.
She says she had to demand the test. “Are you helping to save my life,” she recalls asking her doctor at the time, “or just waiting for me to die?”
That ALK-gene mutation was only the second mutation researchers had identified using advanced DNA-sequencing technology on lung-cancer tumors. The first was in 2004, a mutation in the so-called EGFR gene that responded well to an existing drug, Tarceva, now sold by Roche. (Another mutation, KRAS was discovered previously, with earlier technology.)
The discovery of the role of the EGFR mutation in 2004 sparked the search for more cancer-causing mutations.
Before that, a pathologist would identify a patient’s lung-cancer tumors through a microscope to see if they were of the “small-cell” or “non-small-cell” variety. The difference helped determine which regimen of chemotherapy to prescribe.
After finding the ALK-gene mutation, researchers in 2007 found another mutation. By 2010, for a few lucky patients whose tumors proved to be of the newly discovered varieties, there were a few drugs on the market or in trials.
Ms. Carey was among the fortunate: Her mutation proved to be of the ALK gene, which represents about 5% of lung-cancer cases.
The discovery of the ALK-gene mutation had prompted Pfizer to test a drug already in its portfolio, brand-named Xalkori and generically called crizotinib, to see if it worked on the mutation. Pfizer’s study of the first patients showed dramatic results, which Ms. Carey read about.
Again, Ms. Carey needed persistence, this time to get the drug. She visited different sites participating in Pfizer’s trials before finding a slot at the University of Chicago.
Within six weeks, two of three cancerous nodules in her lungs had disappeared, and the third had shrunk significantly.
The FDA approved the Pfizer drug in 2011 based on 250 patients, four years after the ALK-mutation link was discovered. That is