for the number of patients who experienced tumor shrinkage of 50 percent or greater, as measured by an independent centralized radiology review. This study goal, known as overall response rate, is considered a fast and easily obtainable measurement that is often a leading indicator of whether a cancer drug is doing what’s most important—helping people live longer, and hopefully providing them with high-quality lives. The FDA often wants to see an independent central radiology review of medical images, which can help correct for the bias of physicians who treat the patient directly and want to see them do well on a new drug.
This study, as Siegall has said in the past, would have been considered good enough to seek FDA approval if Seattle Genetics had helped 30 percent of these patients get at least a partial (50 percent) response. Instead, the company is reporting today that 75 percent of patients did that well, and 34 percent went into a complete remission, in which radiologists couldn’t see any evidence of tumors left on their medical images.
Tumor shrinkage can sometimes be an unreliable indicator of success in cancer drug development, because cancer can sometimes bounce back very quickly and resist therapy, killing people just as if no treatment was given at all. Researchers in this study are continuing to follow patients to obtain the gold-standard measurement of overall survival time, but not enough time has passed for them to report with any statistical confidence on whether this drug is helping people live longer, and if so, by how long. That will take more follow up time, Siegall says.
Still, there are some more encouraging early indicators that that this drug will someday prove it can help extend lives. The independent central review found that the median duration of response was a little more than six months (29 weeks) when looking at the whole set of 102 patients. When researchers looked at the one-third who went into complete remission, they still haven’t seen enough relapses after a full year of follow-up to even calculate a median duration of response. That means it will take more follow-up time for researchers to find out just how long the remissions really last.
Side effects were mostly mild compared to conventional chemotherapy. Almost half (47 percent) of patients experienced some degree of peripheral neuropathy, which is nerve damage/tingling in the fingers and toes. Another 46 percent reported fatigue, 42 percent reported nausea, and 37 percent had upper respiratory tract infections during the study. Among the moderate to severe side effects, researchers reported that one-fifth (20 percent) had a depletion of their infection-fighting white blood cells, known as neutropenia. About 8 percent of the cases of peripheral neuropathy were considered moderate to severe. Another 8 percent of patients had significant depletion of clot-forming platelet cells in the blood (thrombocytopenia), and about 6 percent reported a significant knockdown of their oxygen-carrying red blood cells (anemia).
Because of the drug’s high degree of potency, and mild side effect profile, this study is really just the first step for brentuximab vedotin, Chen says. He predicted that “you’ll see the majority of clinicians using this drug,” almost right away for the sickest Hodgkin’s patients, if it is FDA approved. “These patients are really at the end of the line, and this drug really offers them a lot of benefit,” Chen says. “It’s buys them time, and gives them comfort.”
As for the side effects, he says, “they’re all manageable.”
Seattle Genetics is also testing the hypothesis of whether this drug—again because of the high potency and low side effects—has potential to become part of the standard of care
