Much has changed in the last decade except overall survival: A Swiss single center analysis of treatment and survival in patients with stage IV non-small cell lung cancer

Abstract

BackgroundMolecular therapies for cancers with targetable driver mutations and immunotherapies have revolutionized treatment of non-small cell lung cancer (NSCLC) during the last decade. International treatment guidelines began integrating targeted therapies in 2009 and immunotherapies in 2015. The aim of this study was to examine whether the benefits described for these new therapies in pivotal phase III trials have been translated to a real world patient population. Patients and methodsData from all consecutive patients diagnosed with stage IV NSCLC diagnosed at a community hospital in Switzerland between 2007 and 2018 were analyzed. Three groups of patients were compared, namely patients diagnosed before 2009 (group 1), between 2009 and 2015 (introduction of targeted therapies, group 2) and after 2015 (introduction of immunotherapies, group 3). The primary outcome was overall survival (OS). Time to treatment failure was a secondary outcome. Both endpoints were estimated using the Kaplan Meyer method and compared by log-rank test. Results408 patients were included. Patient characteristics were similar in the three groups. Median OS in groups 1, 2, and 3 was 9.8 (95% CI, 6.2 to 13.4), 9.9 (95% CI, 7.6 to 12.1) and 8.6 (95% CI, 6.6 to 10.5) months, respectively (p = 0.5). Across groups patients treated with targeted-and immunotherapies had a significantly better outcome than those treated with chemotherapy or best supportive care (p<0.001). Nevertheless, OS remained unchanged between groups despite adequate molecular testing and integration of targeted-and immunotherapies. Over time, the patient population got more morbid with respect to tumor burden (p = 0.02) and co-morbidities (p = 0.02).

Overall survival and role of programmed death ligand 1 expression in patients with metastatic non-small-cell lung cancer and immunotherapy: an observational study from central Switzerland

“…Our findings of median overall survival with first-and second-line treatments with checkpoint inhibitors were generally consistent with reports of other national and international studies [48][49][50][51].…”

“…[23,28,64,65] Despite the introduction of targeted therapies and immunotherapy and their impact on overall survival, a significant proportion (29.9%) of the patients in our study received best supportive care and not tumour-directed systemic therapy. This proportion is in line with other studies [49,66] and with the results of our previous study on targeted therapies from the same region covering the years 2010-2014 [37]. The rate of best supportive care is consistent with the high proportion of patients with ECOG-PS ≥2 and with the age distribution of our population, which reflects the high proportion of patients with metastatic NSCLC who are elderly and frail and are therefore not considered by clinicians for active treatment of NSCLC [67,68].…”

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

“…This suggests a reduced ICI effect in patients with BM; however, more data from RCTs and larger RWS are warranted. The expected change in overall survival (OS) in patients with advanced NSCLC after the clinical implementation of ICIs has only been sparsely investigated [ 19 , 20 ].…”

“…This suggests a reduced ICI effect in patients with BM; however, more data from RCTs and larger RWS are warranted. The expected change in overall survival (OS) in patients with advanced NSCLC after the clinical implementation of ICIs has only been sparsely investigated [19,20]. This nationwide RWS aimed to compare the OS before and after the implementation of 1L ICI in patients with advanced NSCLC without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) molecular alterations.…”

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

“…These observations seem to suggest that a reduction in incidence coupled with treatment advances, in particular the rise of targeted therapies, is likely responsible for the reduced mortality in NSCLC subgroup. Despite strong evidence, this topic is still a matter of debate [ 125 , 126 ] and further confirmatory studies evaluating the effect of novel targeted therapies, subtype-specific mortality trends and screening, are needed.…”