Still the Right Decision

Gastrointestinal stromal cancer treatment with sutent approval controversy

(RxWiki News) Emotions run rampant and the stakes are high in the billion dollar world of new cancer treatments. Scientists make sure the correct procedures are followed, and no mistakes overlooked.

Recently published research analyzes the drug approval process of Sutent (sunitinib) in 2006, which had the peculiar development of having the phase III trial become unblinded halfway, which meant that patients assigned placebo could switch over to Sutent.

At the time, the researchers cited their analysis, which showed the drug was statistically effective in improving long term survival.

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New research from the Dana-Farber/Harvard Cancer Center, authored by George Demetri, MD, the senior vice president and director, concluded that the U. S. Food and Drug Administration made the correct choice in accelerating approval.

Sutent was approved on the controversial fast-track application process for cases of gastrointestinal stromal tumors that showed resistance to treatment with Gleevec (imatinib). Gleevec is still the only other approved therapy for this form of gastrointestinal cancer, which is most commonly found in the stomach.

"Approval of sunitinib for this indication was extremely rapid," Dr. Demetri stated. "The first [Gastrointestinal stromal tumor] (GIST) patient received sunitinib in 2002, and the interim results led to its approval in 2006. Our final analyses show that this rapid development was appropriate; it did not cut any corners."

"Faster, more reliable clinical trials are needed to enhance the drug development process, and I think that we have shown that these goals really are possible to achieve by designing studies around the best science and choosing diseases that are deeply understood at a molecular level, such as GIST," he added.

Since many patients enroll in drug trials on the assumption that they will be given the most advanced treatments for their cancers, unknowingly belonging in the control group is an unfortunate requirement for researchers to convincingly prove to regulators that the drug works.

The move to allow the patients in the trial to switch treatments was controversial, and reflects on the larger ethical issue which pits the immediate needs of the patients against the possible impact on the data needed for the drug's formal approval, which could affect far more cancer patients.

This was not the case with Sutent, according to the researchers examining the study. Once enough statistical data was banked, the choice was easy.

"We found that sunitinib conferred a clear statistical benefit on overall survival," Dr. Demetri added. "This really is key; it shows that we can design clinical trials that indicate a drug works and offer that active therapy to patients from the placebo arm of the trial — this protects the interests of patients and yet allows the study to provide rigorous proof of the safety and efficacy of the study drug, in this case sunitinib."

The study design followed 243 patients, with 118 in the placebo group.

While strict mathematical interpretation of survival differences between the two groups is impossible, since 103 of the 118 in the placebo switched to sunitinib, acceptable use of substituted mathematical modeling showed a survival increase from 39 weeks with no treatment to 73 weeks with Sutent.

Hard data on the 103 patients that switched treatments showed an average survival of 65 weeks.

Similar to how Gleevec works, Sutent targets a mutation in the cancer gene KIT, preventing it from causing further tumor growth. Sutent was given in a four week on, two week off regime.

Sutent was approved in 2006 by the FDA for both kidney cancer and for treating GIST tumors that do not respond to Gleevec, as a direct result of the phase III study analyzed in this research.

The analysis was published online in the journal Clinical Cancer Research on June 1, 2012.

No relevant financial relationships were made public by researchers.

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Review Date: 
June 14, 2012