By RON WINSLOW

New research is signaling a major shift in how cancer drugs are developed and patients are treated

—offering the promise of personalized therapies that reach patients faster and are more effective than other medicines.

“A pattern is developing at an accelerated pace where we are able to match genetic information about a tumor to a new agent and get results,” says John Mendelsohn, president of Houston’s MD Anderson Cancer Center.

Despite the progress, researchers stress, most personalized treatments don’t necessarily offer a cure. Currently about 800 cancer drugs are in development, many of them designed to target specific mutations. It may take changes in regulatory policy and the development of new diagnostic tests in order for successful therapies to come onto the market. Another issue is cost. The targeted drugs already available run into the tens of thousands a year.

One study led by doctors at Memorial Sloan Kettering, for instance, found that among skin-cancer patients with a mutation in a gene called BRAF, 48% responded to a targeted treatment, compared with just 5% who responded to the current standard treatment.

The report was published online Sunday by the New England Journal of Medicine. Another study, from researchers at Massachusetts General Hospital, suggests that lung-cancer patients with a specific mutation lived significantly longer when treated with a targeted therapy from Pfizer Inc. than a matched group of similar patients who didn’t get the drug.

Both drugs are now on a fast-track review at the U.S. Food and Drug Administration, reaching in the agency in about half the time it takes more conventional medicines to get there.

“We’ve never had more insight into genetic pathways and the genetics of tumors than we do now,” says Gary Gilliland, head of cancer research and development at Merck & Co. These insights are driving “an end-to-end change in the way we develop new drugs for cancer patients and the way we do business.”

By targeting mutations, researchers say fewer patients will be needed to prove the efficacy of new drugs, hastening their path to the market. In addition, fewer people will be enrolled in trials of drugs that provide them little hope of benefit.

But the use in drug development of specific genetic traits in tumors, called biomarkers, poses a maze of challenges. Many tumors are complex organisms fueled by multiple pathways. When one is disrupted even by a potent single agent, others compensate to help tumors develop resistance to treatment. Target therapies will likely be more effective when given along with similar agents or as some are used now, with existing conventional drugs.

In addition, companies developing any drug that targets a specific mutation must also develop a valid companion diagnostic test to identify patients who would be candidates for the treatment. Diagnostic tests are reviewed by part of the Food and Drug Administration that is separate from drug approval, complicating the need to develop the test and drug in tandem, says Mace Rothenberg, senior vice president of clinical development for Pfizer’s oncology business unit.

Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, says the agency also sees the potential for targeted drugs and is working to change regulatory policies to help accommodate these scientific advances. At a recent cancer symposium in New York Dr. Woodcock said, “We are on the tipping point of a whole new game in how we develop drugs [for cancer].”

The targeted skin-cancer drug featured at the ASCO meeting is called vemurafenib and is being developed by Roche Holding AG and Daiichi Sankyo‘s Plexxikon unit. It inhibits a mutated form of a gene called BRAF found in more than half of patients with advanced melanoma and has been shown to have hardly any treatment effect on patients with a normal version of the gene.

Data from a 675-patient trial showed that those taking the drug were 63% less likely to die over a six-month period compared to those taking chemotherapy called dacarbazine. The median time before disease progressed for patients on the drug was 5.3 months compared with 1.6 months on chemotherapy. As a side-effect, the drug caused a benign form of skin cancer in nearly one-fifth of patients that researchers said was easily treated.

The Pfizer drug reported on at the meeting is called crizotinib and it blocks a mutated gene called ALK that is found in up to 7% of patients with a form of lung cancer called non-small-cell lung cancer. In the first report on survival rates benefit from the drug, Alice Shaw, a researcher at Massachusetts General, said 74% of 119 patients treated with the drug were alive after one year and 54% after two years. The study wasn’t randomized, but Dr. Shaw said survival for a comparable set of patients who weren’t treated with crizotinib was 44% after one year and 12% after two years.

Another report featured results from an initiative at MD Anderson Cancer Center involving several experimental drugs in initial, or phase I, testing. Typically, phase I studies of cancer drugs test a single agent in patients to determine a maximum tolerable dose with the hope that a treatment effect might be seen in a couple of patients.

The MD Anderson program pooled 1,144 patients in a phase I study after profiling their tumors for mutations that might be targets of the tested drugs. Apostolia Tsimberidou, the researcher who led the study, reported that 40% had mutations in 10 molecular pathways that were targeted by the experimental compounds.

Tumors in 27% of those given agents that targeted their mutations responded to treatment compared to 5% for those with unmatched therapies.

Other researchers said such a high response rate in a phase I study was highly unusual and could help prompt other academic and corporate researchers to change their protocols to help speed the early-phase trials.

Such testing of patients is also moving into clinical practice thanks to plummeting costs of performing DNA sequencing that researchers use to identify patients’ mutations.

Massachusetts General Hospital and MD Anderson Cancer Center are among institutions beginning to offer routine genetic profiling of tumors for every patient, moving into clinical practice a strategy reserved only for research just a year or two ago and unheard of a decade ago.