Treatment of unresectable stage III non-small cell lung cancer for patients who are under-represented in clinical trials

• Published in: Cancer treatment reviews 2024-09, Vol.129, p.102797, Article 102797
• Main Authors: Bortolot, Martina, Cortiula, Francesco, Fasola, Gianpiero, De Ruysscher, Dirk, Naidoo, Jarushka, Hendriks, Lizza E.L.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; Chemoradiotherapy - methods; Clinical Trials as Topic; Comorbidities; Elderly; Frail; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Neoplasm Staging; NSCLC; Special populations; Unresectable stage III
• ISSN: 0305-7372; 1532-1967; 1532-1967
• DOI: 10.1016/j.ctrv.2024.102797

•Consolidation durvalumab after cCRT is the standard of care for stage III NSCLC.•This approach is debated in some patient populations excluded from clinical trial.•Age, PS 2 and comorbidities are not absolute contraindications for cCRT + durvalumab.•Baseline assessment of ‘fitness’ is mandatory in elderly and frail patients.•Evaluation of treatment’s benefits/risks is essential to avoid unnecessary TRAEs. Concurrent chemoradiotherapy (cCRT) followed by one year of consolidation durvalumab is the current standard-of-care for patients with unresectable stage III non-small cell lung cancer (NSCLC), of good functional status. However, cCRT and consolidation durvalumab may be challenging to administer for selected patient populations underrepresented or even excluded in clinical trials: older and/or frail patients; those with cardiovascular or respiratory comorbidities in which treatment-related adverse events may be higher, and patients with pre-existing autoimmune disorders for whom immunotherapy use is controversial. In this narrative review, we discuss the current evidence, challenges, ongoing clinical trials and potential future treatment scenarios in relevant subgroups of patients with locally advanced NSCLC, who are underrepresented in clinical trials.