Immune boosters show promise against cancer

2012-06-02 10:01
Chicago - A pair of experimental treatments that fight cancer by boosting the immune system have shown promise in early studies and deserve testing in larger patient groups, said US research released on Saturday.

The drugs, both made by Bristol-Myers Squibb, work by breaking down the shield that protects tumour cells. Rather than try to kill the cancer directly, they allow the immune system to do its work against the invading cells.

In the trials which included just over 500 people, as many as one in four patients with non-small cell lung cancer, melanoma and kidney cancer, who had not responded to standard therapies, saw significant shrinkage of their tumours.

Results of the phase 1 clinical trials were published in the New England Journal of Medicine and released at the American Society of Clinical Oncology meeting in Chicago.

The drugs are known as BMS-936558, which blocks a protein PD-1 on the surface of immune cells; and BMS-936559, which blocks a protein PD-L1 expressed on cancer cells.

Scratched the surface

They are in the same class of treatments as other antibody therapies against cancer including Erbitux, Herceptin, and Rituxan.

"We have just scratched the surface of laboratory and clinical research on these drugs," said lead author of the PD-1 study, Suzanne Topalian, professor of surgery and oncology at Johns Hopkins University.

"Based on the positive response rates to these drugs and longevity of many of these responses, we believe that new clinical trials should move forward."

Among the 296 patients who tested in the PD-1 blocking drug, 18% of non-small cell lung cancer patients saw significant tumour shrinkage, as did 28% of melanoma patients and 27% of kidney cancer patients.

A small number of patients, 5% to 9%, saw their disease remain stable for six months or more, though more study is needed to determine the treatment's impact on survival, the researchers said.

"This level of response in patients with advanced lung cancer, which is typically not responsive to immune-based therapies, was unexpected and notable," said lead researcher on the PD-L1 study Julie Brahmer, associate professor of oncology at Johns Hopkins University.

Toxic effects

Among the 207 patients treated with the anti-PD-L1 therapy, 10% of non-small cell lung cancer patients, 17% of melanoma patients, and 12% of kidney cancer patients showed positive responses.

"The positive results from both drugs give us a good indication that the PD-L1/PD-1 pathway is an important target for cancer therapy," said Topalian.

Early analysis showed that among those who responded to the therapy, those responses were maintained for more than a year in half to two-thirds of patients.

However, the treatments also caused serious toxic effects in 14% of patients, including three deaths from lung inflammation, or pneumonitis.

Other significant side effects were colon inflammation and thyroid abnormalities. Some people reported fatigue, itching and rash.

"A major limitation of the various approaches to turning on an immune response to cancer is that the immune system exerts a major effort to avoid immune over activation, which could harm healthy tissues," said an accompanying editorial by doctor Antoni Ribas in the New England Journal of Medicine.

However, Ribas, a melanoma expert at the University of California Los Angeles, pointed out that the treatments may help extend the duration of tumour suppression and could open new doors in personalised treatment.

The research "predicts that these antibodies unleash a memory immune response to cancer", he wrote, adding the approach "may well have a major effect on cancer treatment".

The study authors said the therapies might be most useful if combined with other anti-cancer agents, including cancer vaccines.
Read more on:    cancer  |  health

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