Navigation Links
With early, obvious benefit of a targeted cancer drug, should expensive clinical testing continue?
Date:8/8/2013

Generally, FDA-approved clinical trials progress through three phases: the first shows safety, the second starts to explore effects and the third seeks to prove a drug's superiority over existing treatments. But when a drug's benefit is obvious in the first or second phase, is the third, costly phase needed? The question is posed in a recent edition of the journal Nature Reviews: Clinical Oncology by Robert C. Doebele, MD, PhD, investigator at the University of Colorado Cancer Center and assistant professor of medical oncology at the CU School of Medicine.

Doebele points out the example of the drug crizotinib, which is used to treat a subset of lung cancer patients with a specific gene mutation known as an ALK-EML4 rearrangement. For these "ALK+" patients, crizotinib can be extremely beneficial both the phase I and phase II clinical trials of the drug showed dramatic response in the majority of ALK+ patients treated, even in those with advanced disease who had received prior chemotherapy. In light of these results, the FDA approved the drug in 2011.

But testing continued. Specifically, a phase III trial of crizotinib known as PROFILE 1007 screened 5,000 lung cancer patients and randomly assigned 347 ALK+ patients to treatment with crizotinib or chemotherapy. As everyone expected, crizotinib proved superior in this subset of ALK+ patients, with a progression-free survival of 7.7 months on crizotinib compared to 3 months on chemotherapy, and an overall response rate of 65 percent on crizotinib compared to 20 percent for chemotherapy.

"The question is whether the phase III trial was needed at all," says Doebele.

In addition to continued testing requiring that some patients be randomly assigned to a treatment that most involved expect to be less effective, a phase III clinical test is hugely expensive. "This expense can deter some manufacturers from pursuing promising drugs," Doebele says. For example, imagine a strong candidate drug existed that targeted only 1-2 percent of lung cancer patients knowing the expense of a phase III clinical trial, a drug sponsor may be unlikely to push for approval because the small, eventual market may not justify the cost of testing.

Such is the case for the gene ROS1, which is mutated in 1-to-2 percent of lung cancers. In a phase I clinical trial, lung cancer patients positive for ROS1 fusion showed responses to crizotinib that are nearly identical to those of ALK+ patients. Doebele argues that with genetics showing similarities in the cancer-causing abilities of ALK and ROS1 and with phase I results for crizotinib in the treatment of ROS1 lung cancer so closely matching results in ALK+ lung cancer, the bar for drug approval should be lower. Perhaps a phase II or III trial of crizotinib for ROS1 lung cancer is unneeded?

"This would put some of the burden of monitoring a drug's long-term effects onto clinicians," Doebele says, pointing out that a colleague at the CU Cancer Center noticed the side-effect of low testosterone in some crizotinib patients only after using the drug in clinical practice. "But it streamlines the approval process and gets drugs that are all but proven into the lives of patients who desperately need them."

If the science behind a drug shows it to be rationally targeted at a cancer-causing genetic mutation, and if early clinical trials show the drug is safe and happens to be especially effective, should the drug be held to the same time-consuming and expensive testing standards of traditional chemotherapies? Or is the clinical trials process a relic from the time of earlier, highly toxic therapies? It's an open question.

Doebele writes that, "Targeted therapy for oncogene-positive lung cancer has been proven to induce remarkable tumor responses that are durable and have relatively few adverse effects. Therefore, it is imperative that we develop clinical trials that will accommodate this new paradigm and allow the expedient study and rapid approval of these therapies for patients with oncogene-positive lung cancer."


'/>"/>

Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related biology news :

1. Tumors evolve rapidly in a childhood cancer, leaving fewer obvious tumor targets
2. Natural pest control protein effective against hookworm: A billion could benefit
3. Despite health benefits, most children and adults have a nutrition gap in omega-3 fatty acids
4. Study finds surprising benefits about diary cow inflammation
5. Mapping the benefits of our ecosystems
6. UT Arlington research to benefit quality, flow in 150-mile Integrated Pipeline
7. Gene variants may predict who will benefit from breast cancer prevention drugs
8. First international collaboration to showcase latest body of evidence of dairy health benefits
9. Study finds taking probiotics has benefits for patients in hospitals
10. Sea turtles benefiting from protected areas
11. New research points to benefits of eggs, even for those at cardiovascular risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/28/2020)... , ... May 28, 2020 ... ... has announced a new enzyme solution for adjunct liquefaction: AMYLEX® 6T. The ... the ability to expand into new segments with locally-sourced raw materials, improve ...
(Date:5/21/2020)... ... May 19, 2020 , ... ... provider of operations management solutions, today introduced BioMed to their award-winning computerized ... platform for connecting the people and systems around biomedical engineering to better ...
(Date:5/14/2020)... ... May 12, 2020 , ... ... helps Life Science Manufacturers accurately and easily project contracted liabilities with payers, ... Gross-to-Net models by projecting discounts/rebates to Commercial and Government entities, Copay and ...
Breaking Biology News(10 mins):
(Date:5/5/2020)... ... 2020 , ... Red Nucleus, a leading provider of strategic ... Informa Training Partners, a life sciences training company acquired by Red Nucleus in ... , “The name change solidifies a stronger presence for Red Nucleus in one ...
(Date:4/26/2020)... , ... April 23, 2020 , ... ... Marketplace today, an online store providing applications and services for use on Microsoft ... well-defined business needs to sign up online for a built-for-purpose customer engagement capability ...
(Date:4/22/2020)... ... April 21, 2020 , ... Ripple Science today announced new ... teams are working remotely and have paused patient visits, forcing teams to do ... research during this uncertain time by giving research teams free access to Ripple ...
(Date:4/1/2020)... ... March 30, 2020 , ... Kinetic Vet, an animal ... EPA-approved spray-on antimicrobial solution. As a first-of-its-kind technology within the animal health industry, ... against microorganisms for up to 90 days. , In addition to reducing the ...
Breaking Biology Technology: