New class of cancer drugs shows more promise

Studies have shown the checkpoint inhibitors can help some patients with kidney, bladder, stomach and other cancers

Anew drug that unleashes the body's immune system to attack tumors can prolong the lives of people with the most common form of lung cancer, doctors reported on Friday, the latest example of the significant results being achieved by this new class of drugs. In a separate study, researchers said they had found that a particular genetic signature in the tumor can help predict which patients could benefit from the immune-boosting drugs.

The finding could potentially extend use of these drugs to some patients with colorectal cancer, prostate cancer and other tumors that have seemed almost impervious to the new drugs. Most of the substantial results so far with these expensive drugs have been in treating melanoma and lung cancer. "If you have the signature, you should treat with these checkpoint inhibitors," Luis A Diaz Jr., an associate professor of oncology at Johns Hopkins University and the senior author of the study on the genetic marker, said in an interview, referring to the new drugs.

Both studies were discussed at the annual meeting of the American Society of Clinical Oncology, which began Friday in Chicago. The study on the genetic signature was also published online by the New England Journal of Medicine. The checkpoint inhibitors work by releasing molecular brakes, or checkpoints, that prevent the body's immune system from attacking tumors. The products on the market so far are Keytruda, which is made by Merck, and Opdivo and Yervoy from Bristol-Myers Squibb. All three drugs are approved to treat melanoma, a deadly skin cancer. Opdivo was also approved in March to treat the so-called squamous-cell form of non-small cell lung cancer, which accounts for about one-quarter of the cases of lung cancer.

The new study shows that Opdivo also prolongs survival for patients with nonsquamous cell lung cancer, which accounts for most of the rest of the cases. Patients who received Opdivo lived a median of 12.2 months compared with 9.4 months for those treated with the chemotherapy drug docetaxel. Moreover, Opdivo had far fewer serious side effects.

The trial, paid for by Bristol-Myers, involved 582 patients with advanced cancer who had already had treatment with platinum-containing chemotherapy like carboplatin. In other studies discussed at the conference, Opdivo significantly shrank tumors in 19 percent of patients with advanced liver cancer and Keytruda in 25 percent of patients with head and neck cancer. There is now only one drug approved for liver cancer, Nexavar from Bayer and Amgen.

Other studies have shown the checkpoint inhibitors can help some patients with kidney, bladder, stomach and other forms of cancer. But there have been few signs of effectiveness with colorectal, prostate or pancreatic cancers.

Why do the drugs work so well for some cancers and barely at all for others? One thought is that lung cancer and melanoma are often caused by things that damage DNA - tobacco smoke and ultraviolet radiation. They thus "have tons of mutations, hundreds of mutations per tumor," said Diaz, more than most other tumors. That might make it easier for the immune system to recognise the cancer cells as something to be destroyed.

But some cancers have even more mutations - those with a genetic defect known as mismatch repair deficiency. This deficiency prevents the repair of changes in DNA that can arise as cells divide, allowing mutations to accumulate. The deficiency is found in Lynch syndrome, an inherited condition that puts people at a high risk of developing cancer, particularly colorectal. Lynch syndrome accounts for about 5 percent of colorectal cancers.

To test their hypothesis, the researchers tried Keytruda, in a small study on patients with advanced cancer who were no longer being helped by other treatments. Four of 10 colorectal cancer patients with the deficiency experienced a significant shrinkage of their tumors, according to the paper. That was seen in none of the 18 colorectal cancers without the deficiency. Tumors also shrank in five of seven, or 71 percent, of the patients with cancers other than colorectal that had the mismatch repair deficiency.

DNA sequencing revealed that tumors with the deficiency had an average of 1,782 mutations, compared with only 73 for the tumors without the defect. Genetic tests for mismatch repair deficiency are commercially available. But insurers might not pay for the drugs - Keytruda and Opdivo cost $150,000 a year - based on such a small study.

©2015 The New York Times News Service