Canadian Cancer Trials Group Bulletins


Lung Cancer and Erlotinib: Which Patients Benefit?

The NCI is highlighting BRC.4 -- A Phase III biomarker validation study of second-line therapy in patients with advanced NSCLC randomized to pemetrexed versus erlotinib -- in its current Bulletin. Although not an Canadian Cancer Trials Group-led trial, Canadian Cancer Trials Group was one of the leads in developing BRC.4 and it is based on BR.21.

Canadian Cancer Trials Group BR.21 was the first study to show benefit of the EGFR-molecularly targeted agent, erlotinib, in patients with advanced non-small cell lung cancer who had failed standard chemotherapy regimens (PMID: 16014882). This registration study led to the approval of erlotinib in multiple countries. Canadian Cancer Trials Group BR.21 also evaluated a series of clinical and molecular biomarker predictors of outcome (PMID: 16014883).

Partly as a result of these secondary biomarker analyses, the US NCI recently launched a first-ever Intergroup study, known as MARVEL (aka BRC.4), to prospectively determine if biomarkers can help guide treatment for non-small lung cancer. Although the main goal of MARVEL, to validate the role of EGFR copy number changes as predictive of outcome, will be evaluated by the NCCTG, each of the other cooperative groups will evaluate a secondary set of biomarkers. SWOG will evaluate the role of EGFR activating mutations [Liu, Geoffrey] and measure EGFR gene copy number; ECOG will evaluate proteomic markers. CALGB will evaluate pemetrexed pharmacogenetics. Canadian Cancer Trials Group has been tasked with the evaluation of erlotinib pharmacogenetics.

MARVEL is unique in its primary objective of validating biomarkers as predictors of outcome, and also in its sharing of scientific objectives across multiple cooperative oncology clinical trials groups.

To view the article in the NCI Bulletin, use this link:

The Canadian Cancer Trials Group is currently working towards centrally activating BRC.4.