Over the past decade, immune checkpoint inhibitors have proven to be game changers for the treatment of stage 4 non-small cell lung cancer (NSCLC). Research published this February noted that many patients are living longer after receiving immunotherapy, which activates the body’s own immune system to recognize and kill cancer cells.
While a maximum of two years of immunotherapy has been a standard of treatment, many patients continue treatment beyond that time frame. A new study from scientists at Penn Medicine, however, indicates that it’s reasonable to stop immunotherapy treatment at two years as long as the cancer hasn’t progressed.
Published June 4 in JAMA Oncology and presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, the study indicates that researchers observed no statistically significant difference in overall survival between patients who ended the therapy at two years and those who continued treatment indefinitely.
“These results reinforce what clinical trials have shown us: that two years of immunotherapy may be enough,” says senior study author Charu Aggarwal, MD, an oncologist who specializes in lung cancer at Penn Medicine’s Abramson Cancer Center. “We have the data today to be able to say that physicians and patients should feel comfortable stopping immunotherapy at this point.”
Lung Cancer Survival Rates Similar Whether Immunotherapy Limited to 2 Years or Continued Indefinitely
For the analysis, Dr. Aggarwal and her colleagues reviewed a national electronic health database that included information on patients with advanced NSCLC from both academic and community settings. A total of 1,091 patients received an immune checkpoint inhibitor as part of their initial therapy — either alone or in combination with chemotherapy — and their cancer did not continue to grow.
The average age of participants was 69, about half were female, and about 7 out of 10 were white.
At the two-year mark, only about 1 in 5 patients discontinued immunotherapy, while the others continued the treatment “indefinitely.” Looking at the survival rates, the study authors concluded that participants in neither group were more likely to live longer. Four years after treatment initiation, the probability of survival was 79 percent for those who stopped at two years and 80 percent for those who continued indefinitely.
Why Stop at 2 Years if Outcomes Are the Same?
“A lot of immunotherapy patients say, ‘I'm tolerating this. This is going well. My cancer hasn’t come back. Why would I stop?’” says Aggarwal. “But we must keep in mind that there are financial issues and physical toxicities related to it.”
Aggarwal estimates that immunotherapy costs between $10,000 and $20,000 per month, and insurance may not cover all expenses.
Also, while immunotherapy revs up the immune system to act against the cancer, it can also lead the immune system to act against healthy cells and tissues, warns the Cancer Research Institute. The treatment may trigger flu-like symptoms like fatigue, fever, chills, nausea, muscle aches, and trouble breathing — as well as other symptoms including heart palpitations, sinus congestion, diarrhea, and organ inflammation.
Immunotherapy patients may also experience rash, arthritis, hypopituitarism (when the pituitary gland is not making enough hormones, per Johns Hopkins Medicine), and hypothyroidism (when the thyroid doesn't create and release enough thyroid hormone).
Andrea McKee, MD, a spokesperson for the American Lung Association and chief of the division of radiation oncology at the Lahey Hospital and Medical Center (LHMC) in Burlington, Massachusetts, expects that many immunotherapy patients will welcome the news that the survival benefit seems to remain after two years.
“These patients come once a month to an oncology clinic, infusion center, or hospital, so you can imagine after two years of doing this people are wiped out and have had enough,” says Dr. McKee, who was not involved in the study. “This study goes a long way to reassuring them that they can stop treatment after two years.”
A Revolutionary Treatment for a Leading Cause of Cancer Death
More adults in the United States die from lung cancer than any other type of cancer, according to the Centers for Disease Control and Prevention. About 80 to 85 percent of lung cancers are NSCLC, according to the American Cancer Society.
While immunotherapy has brought great promise to this population, McKee stresses that it doesn’t work for everyone. Johns Hopkins University calculates that 15 to 20 percent of patients achieve durable results with immunotherapy. Research published in the journal Nature puts the patient response rate at 20 to 40 percent.
For the portion of patients who do respond, however, immunotherapy can literally be a lifeline. “We always hate to use the word ‘cure,’ but some of these patients are being cured,” says McKee. “It's a select group of patients who actually have this phenomenal response, and when you do get it, it can be a home run. You can see no cancer growth — no active disease.”
Immunotherapies for NSCLC include Tecentriq (atezolizumab), Imfinzi (durvalumab), Libtayo (cemiplimab-rwlc), Opdivo (nivolumab), Keytruda (pembrolizumab), and Yervoy (ipilimumab).
The study authors noted that there were 11 patients who stopped therapy at two years but then subsequently saw their cancer progress. Eight of them went back on immunotherapy and experienced a median progression-free survival of 8.1 months, which McKee calls “a pretty good response.”
“Immunotherapy is still in its infancy,” she says. “We’re learning so much every few months as to how to use the treatment to better care for our patients and elongate their survival.”
