ELCC News: Biomarker analysis of the TORCH study shows that patients with advanced NSCLC should receive first-line erlotinib only if their tumour harbours EGFR mutations
Patients with unknown or negative EGFR mutation status should be treated with the standard chemotherapy first
- Date: 19 Apr 2012
- Topic: Lung and other thoracic tumours
Patients with advanced non-small cell lung cancer (NSCLC) should only receive treatment with erlotinib before receiving standard chemotherapy if their tumour is known to harbour EGFR mutations, researchers report at the 3rd European Lung Cancer Conference (ELCC) in Geneva, Switzerland (18-21 April, 2012).
The results of biomarker analyses of a the recently reported TORCH clinical trial confirm that patients with unknown or negative mutation status should be treated with the standard chemotherapy first.
Results of the TORCH-BIO study
The TORCH trial was a randomized phase III trial conducted in Italy and Canada, which compared the efficacy of treatment with erlotinib, followed at progression of disease by cisplatin and gemcitabine, against the standard reverse sequence. Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase.
The primary endpoint of the original TORCH study was overall survival and 900 patients were planned, however the study was stopped early as the first interim analysis showed that the erlotinib-first regimen was inferior to the standard approach.
In the new study, Dr Ming Tsao of the Princess Margaret Hospital and colleagues conducted an exploratory analysis on the TORCH patient tumour samples that were available for analysis, looking for molecular biomarkers known to be potential predictors of benefit from EGFR inhibitors.
The results of this secondary analysis show a significant interaction in progression-free survival favouring treatment with erlotinib first in EGFR-mutated patients, and favouring first treatment with chemotherapy in EGFR wild type patients.
However they did not observe a significant interaction between treatment efficacy and overall survival. According to Dr Tsao this shows that using erlotinib to treat patients with a mutated tumour is always effective, both in first and in second line; of course, it is much more convenient for these patients to receive it as first line, as shown also in other trials.
Patients with EGFR mutations benefit from the erlotinib-first regimen because their tumours are very sensitive to the antitumour activity of the drug.
The presenter’s take-home message from this study is that in patients with advanced NSCLC, treatment with erlotinib first should only be applied to patients whose tumour is known to harbour EGFR mutation. Patients with unknown or negative mutation status should be treated with the standard chemotherapy first.
Low tissue accrual rate
Commenting on the study which he was not involved in, Dr Tetsuya Mitsudomi from Aichi Cancer Centre Hospital in Nagoya, Japan said that many previous trials have already shown that EGFR mutation is the most reliable predictive marker for treatment with EGFR-thyrosine kinase inhibitors (TKI). The current analysis was able to confirm the importance of EGFR mutation testing when considering the use of erlotinib, especially in consideration of the far shorter progression-free survival obtained with erlotinib when the mutation was absent. Consequently, although it was thought that erlotinib is active even in lung cancer patients without EGFR mutation if compared with gefitinib, this study suggests that erlotinib should be avoided when treating patients without EGFR mutation, at least in the first-line setting.
This biomarker analysis was preplanned but actually only 36% of the samples could be analysed for EGFR mutation. This relatively low tissue accrual rate is precedented by many clinical trials in which the mutation analysis was performed retrospectively. According to Dr Mitsudomi doctors also have to consider prospective determination of oncogene mutation in order to raise rate such as in NEJ, WJTOG, OPTIMAL and EUROTAC trials.
In summary, the TORCH-BIO study adds important evidence to the research field of EGFR-TKI in advanced NSCLC and emphasizes the importance of biomarker study for improvement of clinical outcome.
The ELCC is organized by top experts in lung cancer and thoracic malignancies from ESMO and IASLC.
Proffered Paper session: Thursday, 19 April, 14:30-16:00, Room A&B