There is nothing like a story that tugs on the heart strings and forces reconsideration of an issue. Take the very sad tale of two close cousins from California who both developed melanoma - Tom McLaughlin landed in the experimental arm of a clinical trial for a Roche drug, PLX4032, while Brandon Ryan was chosen by computer lottery for the placebo. Their plight and the implications were detailed movingly inThe New York Times.
The central issue raised is whether a controlled trial for extending life is ethical. In this instance, PLX4032 was shown to shrink tumors in some patients, but only for a limited time, and the key question was whether those patients would live longer. The standard chemotherapy used in melanoma, dacarbazine, slowed tumor growth in 15 percent of patients for an average of two months, while the Roche drug halted tumor growth in 81 percent of patients for an average of eight months. As the paper notes, some meds may be so much more effective than existing drugs that some docs say putting patients into control groups, and delaying access to thousands of others, is unfair. And many docs believed that if the Roche drug provided relief by shrinking tumors, patient lives would improve.
“With chemotherapy, you’re subjecting patients to a toxic treatment, and the response rates are much lower, so it’s important to answer ‘Are you really helping the patient?’ ” Charles Sawyers, who chairs human oncology at Sloan-Kettering, tells the Times. “But with these drugs that have minimal side effects and dramatic response rates, where we understand the biology, I wonder, why do we have to be so rigorous? This could be one of those defining cases that says, ‘Look, our system has to change.’ ”
Here was the rub: Roche was urged last year to seek accelerated approval. The Times writes, however, that getting patients to join a trial for a drug already on the market was unlikely, since the odds were only 50-50 that a patient would receive the med and patients were already clamoring for the Roche treatment. And without the trial, obtaining "definitive" effectiveness data was also unlikely. Yet the trial would cost $100 million and FDA approval may have to wait two years, which some docs felt was a waste when the important issue was prolonging remissions, the paper adds.
Some docs suggested a combo treatment involving rival meds may be more effective, but Roche refused to give permission for testing. The drugmaker "feared that might lead to approval for only a narrow group of the sickest patients. The surest way to get the FDA’s endorsement for a broader market was a controlled trial. And with its competitors rushing to get similar drugs to market, the findings of such a trial might give Roche an advantage in marketing its version as the only one proven to prolong survival," the paper writes.
The FDA's Richard Pazdur, who heads the Office of Oncologic Drugs, calls the situation "unprecendented," and adds that "regulatory flexibilty" may be in order, according to the paper. Meanwhile, Ryan passed away. “What gives them the right to play God?” Ryan tells the Times. “It doesn’t make sense to say, ‘We want you for a statistic’ instead of giving them a chance at life.” But what do you think?
Are controlled trials for extending life the best way to evaluate cancer drugs?
- Yes (69%, 87 Votes)
- No (31%, 40 Votes)
Total Voters: 127