Immune checkpoint inhibitors in non-small cell lung cancer – When should we dare to stop treatment?

•Currently, immune checkpoint inhibitors (ICI) are administered until progress.•In clinical trials appr. 25% of NSCLC patients complete a two-year ICI treatment.•Persistent response after fixed ICI period is observed in most patients.•Efficacy of ICI rechallenge needs to be determined.•In case of tumor response, fixed ICI therapy duration should be considered. Over the last years, the emergence of immune checkpoint inhibitors (ICI) has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients in a palliative setting with previously very poor prognosis may now show remarkable responses over years. Yet, ICI therapy is very cost-intensive and involves frequent contacts with healthcare resources. Some of the early trial protocols restricted ICI treatment duration to two years. Now follow-up data of these studies is available and reveal the possibility of a persistent response after two or more years without further treatment for patients having successfully completed two years of therapy. May we now dare to think (and speak) of cure in the palliative setting? Does it mean we can stop ICI therapy after an initial two-year treatment? In this review, we try to improve confidence in clinical decision-making for this patient group. To this end, trials with a restricted treatment duration of two years and other data considering potential ICI discontinuation in responding patients were evaluated. Up to 25% of patients successfully complete an initial two-year course of ICI. Within this group about 40–46% of patients are alive at five years without further treatment with five-year survival rates of up to 83%. Data on ICI rechallenge are scarce, yet it does not seem to provide the same level of efficacy as at first exposure. At present there are no established biomarkers to help with decision-making. Possible future (bio-)markers, such as PD-L1, mutations, circulating tumor DNA (ctDNA) or Positron emission tomography (PET) need to be evaluated further in a prospective setting. In conclusion, we propose that the concept of discontinuing ICI therapy in patients with tumor response has to be seriously taken into consideration as it may be of benefit to our patients and health care systems.