Findings by researchers from the University of Pennsylvania should reassure patients and clinicians that stopping immunotherapy for advanced non-small-cell lung cancer (NSCLC) after two years is not detrimental to survival when compared with continuing indefinitely.
“Our study found that for patients who stopped immunotherapy at two years, their survival was not significantly worse than patients who continued immunotherapy beyond two years,” Lova Sun, MD, an assistant professor of Hematology-Oncology at the Perelman School of Medicine at the University of Pennsylvania told Inside Precision Medicine.
“These findings do not imply that everyone should stop immunotherapy at two years, but rather provide reassurance that for patients and providers who are considering stopping at two years, this strategy does not appear to compromise outcomes.”
The retrospective study included data for 706 patients diagnosed with advanced NSCLC between 2016 and 2020 who had no disease progression during their first two years of treatment with frontline immunotherapy.
Notably, at two years fewer than one in five patients eligible for immunotherapy discontinuation stopped treatment, even though patients in key pivotal studies informing the use of first-line immunotherapy use were only treated for up to two years.
“This likely reflects provider and patient uncertainty and anxiety about stopping a treatment that is still working, in a country where the treatment continues to be covered by insurance beyond two years,” said Sun. She continued: “A motivation for our study was to investigate whether this worry was justified, or if stopping at two years is actually a safe approach that does not compromise survival.”
Sun and colleagues report in JAMA Oncology that for the 113 patients who stopped immunotherapy after two years of treatment (fixed duration group), the subsequent two-year overall survival rate was 79%.
By comparison, the two-year OS rate, also measured from two years after treatment initiation, was 81% in the 593 patients who continued treatment beyond two years (indefinite duration group).
There was no significant difference between the two groups in age, sex, race, and tumor characteristics, but patients in the fixed-duration group were significantly more likely to have a history of smoking (99 vs 93%) and be treated at an academic center (22 vs 11%) than those in the indefinite duration group.
Nonetheless, after adjustment for patient- and cancer-specific factors, there was no statistically significant difference in OS between the two groups.
The benefits of stopping immunotherapy at two years include a reduced risk for medical and financial toxicity.
“As with any cancer-directed treatment, long-term treatment with immunotherapy carries significant risk for toxicity [and] prices of these agents, which are dosed every few weeks, remain high,” Sun remarked.
She also stressed that the data do not mean that the clinical benefit of immunotherapy is limited to two years, explaining that the nature of immunotherapy to “reprogram” the immune system to carry out better surveillance and killing of tumor cells, which is sometimes described as creating an “on/off” switch. Immunotherapy can, in some cases, lead to lasting remissions after just a few doses, and for many patients who have not progressed after two years, the clinical benefit may be durable and possibly indefinite, even after stopping treatment.
Sun believes the challenge is now to identify “which patients doing well with long-term immunotherapy are effectively ‘cured’ and can safely stop at any duration, and which really need to continue treatment.”
The study findings were also presented at the 2023 ASCO Annual Meeting in Chicago.