7P - Population-level effect of targeted therapy in patients with advanced pulmonary adenocarcinoma: A Swiss prospective cohort study

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Christine Schwegler
Citation Annals of Oncology (2017) 28 (suppl_2): ii1-ii5. 10.1093/annonc/mdx090
Authors C. Schwegler1, D. Kaufmann2, O. Gautschi3, S. Aebi3, J. Diebold4, D. Pfeiffer4
  • 1Cancer Registry Of Central Switzerland, Cantonal Hospital Lucerne, 6000 - Lucerne/CH
  • 2Institute Of Computer Science, University of Basel, Basel/CH
  • 3Department Of Medical Oncology, Cantonal Hospital Lucerne, Lucerne/CH
  • 4Institute Of Pathology, Cantonal Hospital Lucerne, Lucerne/CH

Abstract

Background

Large cancer centres in the USA demonstrated that molecular diagnosis and targeted therapy improved overall survival (OS) of patients with advanced pulmonary adenocarcinoma (Kris, JAMA 2014). We validated this finding in a rural area of Switzerland, served by private practices, community hospitals, and a tertiary referral centre.

Methods

We conducted a prospective cohort study with the Cancer Registry of Central Switzerland, established in 2010, covering 4 cantons and 517'000 inhabitants. We enrolled all residents newly diagnosed with stage IV pulmonary adenocarcinoma from 2010 until 2014. From the registry, the central pathology and the residents’ offices, we obtained the date of diagnosis and death, gender, smoking, tumour histology and stage, molecular testing (on demand), and therapy. We used the Kaplan-Meier method and a log-rank test to compare OS, and Cox proportional hazards model for association with age, gender and smoking. The cutoff date was February 2016. No adjustment was made for multiple testing. The study was approved by the IRB.

Results

348 patients were included in the study. Median age at diagnosis was 66 years (range, 30-94), 190 (55%) patients were men, 197 (57%) were smokers or former smokers. Molecular testing (PCR, IHC and FISH) was performed in 279 (80%), 132 (38%) had oncogenic driver mutations (ODM): KRAS (17%), EGFR (12%), ALK (6%), HER2 (2%), BRAF (1%), RET (0,5%) or MET (0,5%). 56 patients with an ODM, mostly EGFR (34) and ALK (12), received genotype-matched targeted therapy, at least 25 (45%) of whom in a clinical trial or named patient program. Median OS was 18 months for patients with ODM and targeted therapy, 8 months for patients with ODM and conventional therapy, and 10 months for patients with no ODM and conventional therapy. For patients with ODM and targeted therapy, OS was significantly better than for patients with ODM and conventional therapy (HR 0.64, p = 0.04).

Conclusions

Rigorous testing combined with optimal access to targeted therapy in clinical trials, improved the prognosis of patients with advanced pulmonary adenocarcinoma and EGFR mutation or ALK rearrangement. For patients with tumours lacking actionable mutations, further advances are expected with immunotherapy.

Clinical trial identification

Legal entity responsible for the study

J. Diebold, Institute of Pathology, Cantonal Hospital Lucerne, Lucerne, Switzerland

Funding

Cancer League of Central Switzerland, Lucerne, Switzerland

Disclosure

All authors have declared no conflicts of interest.