By Karen Weintraub
Cancer immune therapy — an approach that harnesses the body’s own disease-fighting system — is saving more patients with more types of cancer, and scientists are getting better at predicting who will benefit, studies released over the last few days show.
Among the findings presented at the annual conference for the American Society Clinical Oncology’s annual meeting, ongoing in Chicago:
•Newer immune-therapy drugs appear to be as or more effective than the first-generation drug, with fewer side effects.
•Genetic fingerprints may help determine which patients will benefit the most from immune therapy.
•Immune therapy may be as or more effective than chemotherapy for some cancer types.
Three years ago this week, cancer immune therapy jumped to prominence when studies revealed that it could extend the lives of people with lung cancer, the biggest cancer killer.
This weekend, at the annual conference of the American Society of Clinical Oncology’s annual meeting – one of the biggest in cancer care – more studies will show the breadth and possibility of immune therapy.
For a century, researchers tried to unleash the power of the immune system against cancer. How could a system that fought off terrible viruses and bacteria be so useless in the face of the body’s own cells?
The potential promise the new wave of therapies is that once the immune system takes control of a tumor, it can search out cells throughout the body, and keep the cancer in check indefinitely.
In studies of melanoma, for instance, where this new approach to immune therapy research began, those patients who responded well to the treatment have survived a nearly universally fatal disease for more than a decade.
About 15% of patients with advanced lung cancer are still alive three years later, according to other research.
“The trajectory for some of these patients are that they’re going to be cured, which obviously is pretty incredible for someone with advanced stage cancer,” said Naiyer Rizvi, director of thoracic oncology and immunotherapeutics at Columbia University Medical Center.
Still, treatment with immune therapies remains largely experimental – “promising” rather than proven approaches.
Supercharging Immune Cells
It took the insight of a Texas researcher named James Allison, now at the MD Anderson Cancer Center in Houston, to make the difference. He realized that rather than supercharging immune cells to fight cancer – which had been tried in vain for decades – researchers needed to release the brakes cancer had placed on the immune system. Once this hold was lifted, the immune system could do its job.
That approach has proven successful across an ever-growing number of cancers – though only for a subset of patients. Three so-called checkpoint blockade drugs have been approved by the Food and Drug Administration for advanced melanoma, and one of those, Opdivo from Bristol-Myers Squibb received approval for treating advanced squamous non–small cell lung cancer.
“The indication we have so far is that these drugs are superior to the drugs that are already in standard use for these cancers,” said Dr. Suzanne L. Topalian, director of the Melanoma Program at Johns Hopkins Kimmel Cancer Center in Baltimore. More head-to-head comparisons are needed to confirm these results, she added.
Treatment with Opdivo on its own or combined with the first-generation checkpoint blockade Yervoy, also by Bristol-Myers, is more effective than Yervoy alone, a study released Sunday showed. The combination also helped more melanoma patients – 58% – compared to 44% of those taking Opdivo alone and 19% of those taking only Yervoy.
The research is so new, Topalian said, that it’s still unclear exactly how long patients should take Opdivo or a similar drug from Merck called Keytruda – which each cost as much as $150,000 a year. Right now, these drugs have been approved only for advanced cancers, but doctors are already beginning to to test them in clinical trials for patients who are earlier in the disease process, she said.
Studies have also shown these checkpoint blockade drugs can help some – but far from all – patients with breast, bladder, head and neck, liver, gastric, Hodgkin’s lymphoma and other cancers.
Researchers have worked to identify the subset of patients – sometimes as few as 10% of a cancer type – who are most likely to benefit from checkpoint blockade drugs, rather than subjecting every patient to expensive, potentially difficult therapy.
Another new study from researchers at Johns Hopkins University showed that genetic clues may be more important than cancer type in suggesting which patients are most likely to respond to checkpoint blockade therapy.
Scientists also hope to expand the pool of patients who will benefit from immune therapy. In research labs and clinical trials all over the world, researchers are testing these checkpoint blockade drugs in combination with other immune therapy approaches like vaccines, and with chemotherapy, radiation and targeted therapies, which they hope will help more patients live longer.
Topalian said she’s also hopeful that more types of cancers will become vulnerable to checkpoint blockades when given in combination with other therapies. Patients with prostate cancer, for instance, have not done well on checkpoint blockades, she said, but she hopes a combination can be found that will help them, too.
Checkpoint blockade seems to work best when immune cells have already found and congregated in a tumor – then, lifting the brake unleashes them against the cancer. In the majority of cancer patients and some cancer types, there aren’t enough immune cells in the tumor to win the war. A different type of treatment that drives immune cells into the tumor might make all the difference, Topalian said.
Advances are also happening in other types of immune therapy. In one small trial, which was the subject of a 60 Minutes eature, researchers used a reengineered polio virus to attack glioblastoma, the deadliest form of brain cancer. Other immunotherapy work, led by Dr. Carl June at the University of Pennsylvania, has shown tremendous progress against blood cancers, though it’s still being used in a small minority of patients.
Hype And Caution
And all this work remains far from a cure for cancer. Doctors are even afraid to use that word, having been burned so many times by promising therapies that failed to deliver.
But immune therapy has come farther than many of these other approaches, and the last three years has seen an explosion of attention – “a blaze in the world of pharma,” as Topalian puts it – with thousands of clinical trials and tens of thousands of patients.
“Patients are really clamoring to participate in these trials,” said Rizvi, of Columbia University. He’s using immune therapy regularly now; sometimes before chemotherapy.
Despite both the hype and caution, it is clear that immune therapy will increasingly become a pillar of cancer treatment, along with surgery, chemotherapy and radiation.
In one late-stage clinical trial presented this weekend, non-small cell lung cancer patients who received Opdivo had fewer side effects and were more likely to respond and live longer than those treated with chemotherapy.
“The results we have so far are really quite exciting,” Topalian said, “but we are still at the beginning of the story.”