Population-level effect of molecular testing and targeted therapy in patients with advanced pulmonary adenocarcinoma: a prospective cohort study

Abstract

Large cancer centres in the USA demonstrated that molecular diagnosis and targeted therapy improved overall survival of patients with advanced pulmonary adenocarcinoma. We validated this finding in a rural area of Switzerland, served by private practices, community hospitals and a tertiary referral centre. We conducted a prospective cohort study with the Cancer Registry of Central Switzerland, covering 4 cantons and 517,000 inhabitants. All residents newly diagnosed with stage IV pulmonary adenocarcinoma from 2010 to 2014 were enrolled. We obtained information on patients, tumour, molecular testing, therapy and survival. Three hundred forty-eight patients were included in the study. Molecular testing was performed in 279 (80%); 132 (38%) had oncogenic driver mutations: Kirsten rat sarcoma (KRAS, 16%), epidermal growth factor receptor (EGFR, 11%), anaplastic lymphoma kinase (ALK, 5%), human epidermal growth factor receptor 2 (HER2, 2%), B rapidly accelerated fibrosarcoma (BRAF, 1%), rearranged during transfection (RET, 0.5%), MET proto-oncogene (0.5%) and multiple mutations (2%). Fifty-six patients with an oncogenic driver mutation, mostly epidermal growth factor receptor (34) and anaplastic lymphoma kinase (12), received genotype-matched targeted therapy, at least 25 (45%) of whom in a clinical trial or named patient programme. Median overall survival was 18 months for patients with driver mutations and targeted therapy, 8 months for patients with driver mutations and conventional therapy and 10 months for patients with no driver mutation and conventional therapy. For patients with driver mutations and targeted therapy, overall survival was significantly better than that for patients with driver mutations and conventional therapy (HR 0.64, p = 0.04). Rigorous testing combined with optimal access to targeted therapy in clinical trials improved the prognosis of patients with advanced pulmonary adenocarcinoma in Central Switzerland. This effect was mainly driven by therapies targeting epidermal growth factor receptor and anaplastic lymphoma kinase.

Keywords: Chemotherapy; Molecular diagnosis; Population study; Targeted therapy.