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

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.

Comparison of two ERCC1 antibodies as prognostic and predictive biomarkers for early non-small cell lung cancer.

AIM: Expression of excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) was suggested to be of predictive value for selecting patients with clinical benefit from platinum-based chemotherapy. PATIENTS AND METHODS: In order to validate the prognostic and predictive value of ERCC1, we comparatively analyzed 298 patients with non-small cell lung cancer (NSCLC) treated with and without platinum-based adjuvant chemotherapy with two different antibodies against ERCC1 (clones 8F1 and SP68). RESULTS: We found that both antibodies have a different immunoreactivity, with SP68 showing a more distinct, predominantly nuclear staining pattern. There was no prognostic effect for patients with high compared to patients with low ERCC1 expression, regardless of the antibody applied. In contrast, patients with squamous cell carcinoma treated with adjuvant platinum-based chemotherapy who had a low ERCC1 expression had a survival benefit with respect to disease-free and overall survival. This was especially true for expression by the SP68 antibody. CONCLUSION: Oour data point to a potential predictive value of ERCC1 expression for the selection of adjuvant platinum-based chemotherapy for patients with pulmonary squamous cell carcinomas but not for those with adenocarcinomas. With more specific antibodies in hand, this should be substantiated in subsequent clinical studies.