Landmark study provides insight into chemotherapy treatment for lung cancer patients
13 January 2017
A research team, led by UCL, has published the results of a highly anticipated clinical trial comparing platinum and non-platinum chemotherapy in the Journal of Clinical Oncology. The aim of this trial was to see whether doctors could select the most effective chemotherapy treatment for advanced lung cancer patients.
The ERCC1 trial is the first and only randomised clinical trial to definitively evaluate whether chemotherapy without platinum drugs works better than platinum-based chemotherapy in patients with advanced lung cancer who have high levels of a body protein called ERCC1.
Platinum-based chemotherapy is widely used to treat advanced Non-Small-Cell Lung Cancer (NSCLC). However, only approximately 30-40% of patients responded to platinum chemotherapy treatment. One of the reasons for this may be to do with specific DNA repair proteins affecting how chemotherapy works - which is where ERCC1 comes into play.
ERCC1 is a protein that helps to repair DNA damage to cancer cells caused by platinum drugs. It is thought that high levels of this protein is associated with platinum resistance in NSCLC, and research several years ago suggested that ERCC1 is a ‘predictive biomarker’. As a consequence it has been used in clinical practice to determine which type of chemotherapy is selected.
But should ERCC1 be used in this way? According to the study results, the answer to this question is ‘no’. Professor Siow Ming Lee, Consultant Oncologist UCLH, Professor of Medical Oncology, UCL and lead author of the study explains: “To conduct the trial, we established first whether participants with advanced NSCLC were ERCC1-positive or ERCC1-negative (high or low levels of ERCC1 respectively). We then split everyone according to the type of lung cancer: in this case, squamous or non-squamous. Patients were then randomly given platinum or non-platinum chemotherapy and the outcomes (relapse and mortality) compared.”
“Given the association between ERCC1 and platinum resistance, we would expect the non-platinum therapy to be more effective than the platinum therapy in ERCC1-positive groups.” says Professor Lee, “However, this was not the case for both squamous and non-squamous NSCLC. In fact, what is very striking is that outcomes were significantly worse in the squamous histology group given non-platinum therapy regardless of their ERCC1 status. So much so, the trial had to be stopped early for the squamous patients, to allow them to be switched to platinum therapy.”
“To our knowledge, this is the first time any randomised trial has shown superior outcomes among squamous NSCLC treated with platinum versus non-platinum therapy, and these patients should continue to have this.” says Professor Lee.
The results have important implications for clinical practice, in that ERCC1 should not be used to determine who should get platinum or non-platinum chemotherapy, and to reinforce the importance of platinum drugs in treating lung cancer.
The research was funded by Eli Lilley, Cancer Research UK and NIHR UCLH Biomedical Research Centre.
- Research paper: Randomized Prospective Biomarker Trial of ERCC1 for Comparing Platinum and Nonplatinum Therapy in Advanced Non-Small-Cell Lung Cancer: ERCC1 Trial (ET) in the Journal of Clinical Oncology
- Professor Siow Ming Lee consultant profile
- Cancer Research UK-UCL Clinical Trials Centre
- NIHR UCLH Biomedical Research Centre
- Cancer Research UK Lung Cancer Centre of Excellence
- Image: Lung - cancerous and noncancerous cells. Steve Bagley, Cancer Research UK Manchester Institute