Can a combination of targeted treatments work better than one in non-small cell lung cancer?

This study investigated the effect of erlotinib (Tarceva) with high dose celecoxib (Celebrex) in patients with advanced non-small cell lung cancer.

Some non-small cell lung cancers develop and grow due to a mutation (abnormality) in the epidermal growth factor receptor (EGFR) gene. EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, target and inhibit (block) EGFR. It is not clear how helpful EGFR TKIs are for patients who do not have an EGFR mutation.

Cyclooxygenase 2 (COX-2) is an enzyme that is also involved in the growth of some non-small cell lung cancers. COX-2 can be inhibited by treatments such as celecoxib. It is thought that treatment with celecoxib may increase the response to erlotinib.

The current study examined whether a combination of erlotinib and celecoxib was more beneficial than erlotinib alone in patients with non-small cell lung cancer. 109 patients were randomly assigned to receive either a combination of erlotinib and celecoxib (Group 1) or erlotinib and placebo (a substance with no effect on the body; Group 2). 57% of patients in Group 1 and 51% in Group 2 did not have an EGFR mutation. Patients were followed for an average of 12.1 months.

Patients without an EGFR mutation in Group 1 saw a significant improvement in progression free survival time (time from treatment until disease progression, 3.2 months) compared to those in Group 2 (1.8 months). There was no difference in progression free survival between the two groups in patients with an EGFR mutation.

High levels of PGEM (a substance that indicates inflammation and time to tumor progression) were found in some patients. Group 1 patients with high levels of PGEM before treatment had a longer progression-free survival time (5.4 months) compared to patients in Group 2 with high PGEM (2.2 months). No difference was found in patients with low levels of PGEM.

This study concluded that non-small cell lung cancer patients who do not have an EGFR mutation may benefit from treatment with both erlotinib and celecoxib, particularly patients with high levels of PGEM.

Astetellas Pharmaceuticals, the manufacturer of erlotinib, and Pfizer, the manufacturer of celecoxib, provided funding for this study.