Drugs in the pipeline: new therapies that could change treatment strategies

Adding bevacizumab to standard chemotherapy and radiation in patients with rectal cancer fully prevented tumor spread and “normalized” tumor blood vessels enough to enable effective therapy, researchers report.

“I know of no other therapy in this patient population where we can even get close to 100 percent tumor control. Although this needs to be confirmed in a randomized trial against a placebo group, these are very impressive numbers,” said Rakesh Jain, Ph.D., Andrew Werk Professor of Tumor Biology at Harvard Medical School.

Bevacizumab is currently approved for colorectal cancer, and works by destroying the blood vessels that tumors need to grow.

“This mechanism of action was a conundrum for scientists because in order for radiation and chemotherapy to work, you need blood vessels,” Jain said. “However, the current study adds evidence to a concept called normalization whereby restoring order to blood vessels inside a tumor opens up a window of opportunity for treatment.”

Blood vessel normalization allows the vessels that remain to perform more efficiently. “With a drug like bevacizumab, some of the tumor vasculature is pruned away immediately, but the vessels that remain become less abnormal,” Jain said. “These normalized vessels make the surviving cancer cells more vulnerable to the treatments that can now be delivered more efficiently. Cancer therapies in this environment should be maximally effective.”

In the current study, researchers enrolled 24 patients with late-stage rectal cancer. All patients completed four cycles of therapy including bevacizumab, additional standard chemotherapy, radiation and surgery.

At four years, local control, or the absence of cancer spread beyond the original tumor site, was observed in 100 percent of patients and disease-free survival in 88 percent.

Of the 24 patients treated, five had no residual cancer. Of the 19 patients with residual disease, 12 displayed severe disease. Downstaging of the tumor was observed in 12 out of 22 observable tumors.

“We had shown in previous mouse studies that normalizing blood vessels would decrease tumor activity, but the question with mouse studies is whether it will work in humans,” Jain said. “This is the first study to confirm the idea of the effect of normalization in patients.”

Preliminary results of a Phase I study of AME-133v, an Fc-engineered humanized monoclonal antibody, in low-affinity Fc?RIIIa patients with previously-treated follicular lymphoma: LB-70

A second generation, highly targeted monoclonal antibody appears to provide benefit for some patients with follicular lymphoma for whom other treatments have failed, according to results of a phase I clinical trial.

In the 16 patients evaluated so far, four have achieved either a partial or complete response with use of the novel agent AME-133v, said the study’s lead investigator, Andres Forero, M.D., associate scientist at the University of Alabama, Birmingham, Comprehensive Cancer Center.