‘Paradigm shift’ in lung cancer care

April 17, 2018 GMT

Lung cancer patients live longer when treated as early as possible with drugs that enlist the immune system, according to new research expected to extend the therapy pioneered by a Houston scientist to tens of thousands more people with the usually fatal disease.

The research, presented Monday at a cancer conference in Chicago, represents another step forward for a type of immunotherapy that removes an immune system brake to unleash the body’s defenses to attack tumors. MD Anderson Cancer Center immunologist Jim Allison identified the brake and developed the first drug based on its release.

“Based on this research, I expect 90 percent of lung cancer patients will start treatment with immunotherapy within the next year,” Dr. John Heymach, chairman of thoracic/head and neck medical oncology at MD Anderson and a conference panelist, said about the studies. “It’s a watershed moment in the history of lung cancer treatment.”

Heymach said the positive data presented in studies at the conference represents the greatest set of advances ever made in a single period of time in the fight against lung cancer, and Allison added that it suggests that chemotherapy as “a lone treatment for the disease is on its way out.”

Lung cancer is the nation’s No. 1 killer, claiming more than 150,000 lives annually, 11,000 of them in Texas. More than 230,000 new cases are diagnosed every year, the vast majority after cancer cells have already spread to other organs. In such cases historically, the vast majority of patients rarely lived more than a few years.

Studies presented at the American Association for Cancer Research conference found that front-line immunotherapy, either in combination with chemotherapy or a second immunotherapy drug, benefited patients more than chemotherapy alone, the current standard of care. Currently, most patients don’t get immunotherapy until after they’ve already taken chemotherapy and some never do because they die before they can go on such drugs.

Great success story

Immunotherapy has become cancer treatment’s great success story this decade, producing lasting benefits in a number of metastatic cancers historically considered death sentences. But such successes have come in a minority of patients. The new data is the first to show it can benefit a majority of patients with a particular cancer and work best as front-line therapy.

The most impressive results came in a study that paired chemotherapy and a “checkpoint inhibitor,” the class of brake-releasing drugs originated by Allison. At one year, the combination cut in half patients’ risk of dying or having the cancer worsen, compared to those who received chemotherapy alone.

A second study found two checkpoint inhibitors taken together, one Allison’s drug, worked better than chemotherapy alone for delaying the time until cancer worsened in a subset of advanced lung cancer patients with particular genetic mutations. Such patients’ cancer was 42 percent less likely to progress than those on chemo.

A first option

Among patients who received combination immunotherapy is Cecil Joiner, a 76-year-old Conroe insurance agent only diagnosed after X-rays taken after he fell from his golf cart last autumn showed no broken bones but a tumor in his lung. At MD Anderson, he was offered three front-line options: chemotherapy, surgery or immunotherapy.

“I wasn’t crazy about chemotherapy, given the debilitating effects I’d seen in others, and I liked the idea of providing drugs that enlist the immune system to work,” said Joiner. “I opted for the immunotherapy, which involved three infusions of the two drugs, then follow-up surgery two months later.”

Joiner, who suffered neither cancer symptoms nor treatment side effects and is back to playing golf, said he’s “very pleased” with his decision.

His treatment is part of an MD Anderson study, not presented at the AACR meeting but mentioned by Heymach as one of a number of ongoing efforts to investigate numerous possible combinations of immunotherapy and other treatments for lung cancer. He said the goal one day will be to eliminate the need for chemotherapy, though researchers still have work to do to reach that point.

Heymach estimated that between 50 percent and 60 percent of lung cancer patients currently get immunotherapy at some point and that 30 percent to 40 percent get it as front-line therapy. He said that number has been rising very sharply recently.

Definitive evidence

Keytruda, the drug used with chemotherapy in the study presented Monday, was approved last year for such front-line combination treatment against the most common form of advanced lung cancer. But many doctors have been slow to use it because the study that led to its approval was small and didn’t show whether the treatment prolonged survival.

The new study, which included 616 randomly chosen patients with advanced lung cancer and lacking the mutations that would have made them candidates for more targeted treatments, provides more definitive evidence. At one year, nearly 70 percent of those who received Keytruda and chemotherapy were alive, compared to 49 percent of those who received only chemo. That difference came even though the latter group’s number was improved because half ultimately ended up switching.

“In my 25 years of treating lung cancer, I have never seen such a paradigm shift as we’re seeing with immunotherapy,” Dr. Roy Herbst, chief of medical oncology at Yale Cancer Center and a former MD Anderson administrator, said during the panel discussion Monday. “If you want to see long-term survival, you’ve got to give immunotherapy as soon as possible.”