The approval of immune checkpoint inhibitors has revolutionised treatment for patients with advanced lung cancer, helping many live longer lives and improving overall survival for the disease, but researchers have found no difference in overall survival if the immunotherapy is halted after two years.
An important question has always been how long a patient – with advanced non-small cell lung cancer (NSCLC) and who receives immunotherapy – should continue with treatment.
Now, a retrospective cohort study, presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting by researchers from Penn Medicine’s Abramson Cancer Centre and published in JAMA Oncology, suggests it’s reasonable to stop immunotherapy treatment at two years as long as the cancer hasn’t progressed.
The researchers found no statistically significant difference in overall survival between patients who stopped treatment at 24 months and those who continued treatment indefinitely.
Lead author Dr Lova Sun, an assistant professor of Haematology-Oncology at the Perelman School of Medicine at the University of Pennsylvania, said: “In the absence of definitive prospective data about the duration of therapy – which will take years to accumulate – our goal was to use real-world observational data to provide guidance on this important clinical question.”
The appropriate length of treatment remains an open question because pivotal clinical trials have used different treatment durations, and as therapies have been approved and become widely available, many patients have continued therapy beyond the one to two years tested in clinical trials.
The longer a patient continues treatment, the higher the health care costs become – both to the patient and to the healthcare system – and there is ongoing risk of immune-related side effects.
In the study, the researchers analysed de-identified data from a national electronic health record that included patients with advanced NSCLC who were treated in both academic and community settings.
Of the 1 091 patients who received an immune checkpoint inhibitor as part of their initial therapy (either alone or in combination with chemotherapy) and whose cancer had not continued to grow, only one in five stopped immunotherapy at two years and were considered the “fixed duration” group for this analysis.
The vast majority who continued treatment beyond two years were considered the “indefinite duration” group.
The team analysed the data and found similar overall survival probabilities between the two groups: 79% for fixed duration and 81% for indefinite duration.
“Ultimately, the field is still on the leading edge of determining the most appropriate duration for these immunotherapies that have been so effective for patients with advanced lung cancer,” said senior author Dr Charu Aggarwal, the Leslye M Heisler Associate Professor for Lung Cancer Excellence in Haematology-Oncology at Penn.
“This study provides important data that we hope will help patients feel less worried about potential risks of coming off therapy and more confident if they decide to discontinue treatment after two years.”
Study details
Association between duration of immunotherapy and overall survival in advanced non–small cell lung cancer
Lova Sun, Benjamin Bleiberg, Wei-Ting Hwang, et al.
Published in JAMA Oncology on 4 June 2023
Abstract
Importance
For patients with advanced non–small cell lung cancer (NSCLC) treated with frontline immunotherapy-based treatment, the optimal duration of immune checkpoint inhibitor (ICI) treatment is unknown.
Objective
To assess practice patterns surrounding ICI treatment discontinuation at two years and to evaluate the association of duration of therapy with overall survival in patients who received fixed-duration ICI therapy for two years vs those who continued therapy beyond two years.
Design, Setting, and Participants
This retrospective, population-based cohort study included adult patients in a clinical database diagnosed with advanced NSCLC from 2016 to 2020, who received frontline immunotherapy-based treatment. The data cut-off was August 31, 2022; data analysis was conducted from October 2022 to January 2023.
Exposures
Treatment discontinuation at two years (between 700 and 760 days, fixed duration) vs continued treatment beyond two years (greater than 760 days, indefinite duration).
Main Outcomes and Measures
Overall survival from 760 days was analysed using Kaplan-Meier methods. Multivariable Cox regression that adjusted for patient-specific and cancer-specific factors was used to compare survival beyond 760 days between the fixed-duration group and the indefinite-duration group.
Results
Of 1 091 patients in the analytic cohort who were still on ICI treatment at two years after exclusion criteria for death and progression were applied, 113 patients (median [IQR] age, 69 [62-75] years; 62 [54.9%] female; 86 [76.1%] White) were in the fixed-duration group, and 593 patients (median [IQR] age, 69 [62-76] years; 282 [47.6%] female; 414 [69.8%] White) were in the indefinite-duration group. Patients in the fixed-duration group were more likely to have a history of smoking (99% vs 93%; P = .01) and be treated at an academic centre (22% vs 11%; P = .001). Two-year overall survival from 760 days was 79% (95% CI, 66%-87%) in the fixed-duration group and 81% (95% CI, 77%-85%) in the indefinite-duration group. There was no statistically significant difference in overall survival between patients in the fixed-duration and indefinite-duration groups, either on univariate (hazard ratio [HR] 1.26; 95% CI, 0.77-2.08; P = .36) or multivariable (HR 1.33; 95% CI, 0.78-2.25; P = .29) Cox regression. Approximately 1 in 5 patients discontinued immunotherapy at two years in the absence of progression.
Conclusions and Relevance
In a retrospective clinical cohort of patients with advanced NSCLC who were treated with immunotherapy and were progression-free at two years, approximately only one in five discontinued treatment. The lack of statistically significant overall survival advantage for the indefinite-duration cohort on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at two years.
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