Immunotherapy in non-metastatic non-small cell lung cancer: Can the benefits of stage IV therapy be translated into earlier stages?

Abstract

Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC. Aside from chemotherapy and targeted therapy, immunotherapy has become the third pillar in the treatment armamentarium of advanced NSCLC. Antigen-specific immunotherapy (cancer vaccination) has been disappointing in large phase III clinical trials in stages I–III NSCLC. Based on the recent breakthroughs with immune checkpoint inhibitor immunotherapy in metastatic NSCLC, much hope currently rests on the use of this approach in patients with stage I–III NSCLC as well. Here we give a brief overview of how most new therapeutic approaches for advanced NSCLC failed in other stages, and then elaborate on the role of immunotherapy in patients with stage I–III NSCLC.

Immunotherapy-based combination strategies for treatment of gastrointestinal cancers: current status and future prospects

“…With the success of immune checkpoint blockade in the late stage of cancer, its possible application as front-line or even adjuvant therapy to mobilize host anti-tumor immunity at the early stage of disease in immunosuppressive microenvironment has not been induced by multiple therapies or tumor evolution and is preferred to be investigated [90]. Neoadjuvant immunotherapy was assessed in NSCLC.…”

Innovations in the treatment of non-small cell lung cancer

“…Grills et al 32 suggest incidental dose to the regional nodes, differences in follow-up and a higher non-cancer death rate after SABR to result in possible 'underestimation' of nodal failures. The theory of sterilisation of micrometastases through incidental mediastinal/hilar dose is supported by the observations of Lao et al 16 amongst others, however, it is still a matter for debate 46 .…”

“…Some treatment planning systems already allow the evaluation of plan robustness. Furthermore, consideration of robustness cannot only be included in the treatment plan evaluation step, but also in the plan optimisation (robust optimisation) [43][44][45][46] . Usually this will result in decreased quality of the nominal treatment plan in combination with smaller deviations between nominal and actual dose distribution under the influence of setup uncertainties and intra-and inter-fractional motion.…”

“…For patients with locally advanced NSCLC, only modest improvements in outcome have been reported over the last decade 46 . In a retrospective cohort study, we showed that metformin may be beneficial in this patient category as fewer distant metastases occurred and progression free survival was longer in patients using metformin during concurrent chemoradiotherapy.…”

“…The dose to the planning target volume (PTV) is most conformal in the modulated arc plan as less dose is deposited in healthy surrounding tissues. Abbreviations: 3D-RT= three-dimensional conformal radiation therapy, s-IMRT = static intensity modulated radiotherapy, mARC = modulated arc (figure adopted from Choi et al46 ).…”