For patients battling late-stage lung cancer, prospects for survival have improved significantly since the advent of medications known as immune checkpoint inhibitors.
But exactly how long patients with advanced non-small cell lung cancer (NSCLC) need to be on immunotherapy has not been known. Until now.
According to new research involving more than 1,000 patients, those with stable disease can stop the treatment after two years without jeopardizing their survival odds. (“Stable” means their lung cancer shows no sign of progression.)
Investigators found that those who stopped at 24 months fared just as well as patients who continued to take the medication indefinitely.
Moreover, discontinuing immunotherapy at two years might diminish the risk for downsides that can accompany open-ended inhibitor treatment, the researchers said.
“Long-term treatment with immunotherapy carries significant risk for toxicity,” explained study lead author Dr. Lova Sun, an assistant professor of hematology-oncology with the University of Pennsylvania School of Medicine, in Philadelphia.
Sun pointed out that immunotherapy is also quite expensive, so the longer patients stay on the treatment, the higher their potential out-of-pocket cost, depending on insurance.
According to the U.S. National Cancer Institute, immune checkpoint inhibitors also pose a risk for a wide array of side effects, including rashes, diarrhea and fatigue. In rare cases, the treatment may also trigger widespread inflammation, which can interfere with proper organ function.
Targeted immunotherapy drugs include pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo) and atezolizumab (Tecentriq).
They work by preventing tumor cells from undermining a key weapon in the immune system: T-cells.
T-cells can be effective at killing off cancer cells. The problem is that when lung cancer develops, proteins found on tumor cells end up finding and binding with specific proteins found on T-cells. The result: T-cells get turned off.
But immune checkpoint inhibitors can stop that binding from happening in the first place. In so doing, the treatment preserves a T-cell’s cancer-fighting power.
For this work, investigators studied roughly 14,400 patients with advanced NSCLC, using information from a national U.S. electronic database.
All were aged 18 years or older when diagnosed with NSCLC between 2016 and 2020. And all had received immunotherapy, sometimes in conjunction with chemotherapy.
Two years after the start of immunotherapy, only about 1,100 patients were still alive, had not started any additional treatment, and had cancer that was stable.
Among this group, one-fifth had stopped taking immune checkpoint inhibitors precisely at the two-year mark. All who continued the treatment beyond that point were characterized as “indefinite” treatment patients.
After comparing survival rates among both groups, the study team found nearly identical results: 79% survival among those who stopped treatment versus 81% among the ongoing treatment group. The difference was deemed to be “statistically” insignificant.
The findings are “quite appealing,” said Sun.
Moreover, “for a small group of patients who stopped at two years and then progressed, many of them were able to restart the same medication with clinical benefit,” she added.
But that suggests patients taken off immune checkpoint inhibitors should continue to be monitored, and “immunotherapy re-challenge should certainly be considered,” Sun noted.
Dr. Thomas Marron is director of the early-phase trials unit at the Tisch Cancer Institute of Mount Sinai, in New York City.
For lung cancer patients, he said immune checkpoint inhibitors have essentially doubled life expectancy and likely cured cancer altogether among somewhere between 10% and 30% of patients.
In effect, “immunotherapy is curing what was previously incurable cancer,” said Marron, who was not part of the study team.
Still, he noted that the “financial toxicity to patients” on the treatment for years is significant, even for wealthy patients, depending on where they live and their insurance.
“Along with co-pays for therapy,” explained Marron, “you have to consider the co-pays for all the blood tests and imaging assessments, which can be high, as well as the transit to and from the cancer center every few weeks for years.”
Side effects from long-term treatment are also a legitimate concern, he added.
Also, some patients and their doctors “are nervous to stop therapy” when things appear to be going well, he acknowledged. But the preponderance of research suggests “that most patients who are in remission at two years stay in remission upon cessation,” Marron said.
The findings were published online June 4 in JAMA Oncology and presented at the annual meeting of the American Society of Clinical Oncology, in Chicago.
The U.S. National Cancer Institute has more on immune checkpoint inhibitors.
SOURCES: Lova Sun, MD, assistant professor, hematology-oncology, University of Pennsylvania School of Medicine, Philadelphia; Thomas Marron, MD, PhD, director, early-phase trials unit, Tisch Cancer Institute of Mount Sinai, New York City; JAMA Oncology, June 4, 2023, online