Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: A phase II clinical trial


Imatinib Mesylate Lacks Activity in Small Cell Lung Carcinoma Expressing c-kit Protein: A Phase II Clinical Trial

We read with great interest the article by Krug et al.1 In their Phase II, single-institution study, single-agent imatinib was tested in patients with recurrent small cell lung carcinoma (SCLC) whose tumor specimens expressed c-kit protein based on the presence of c-kit protein expression in SCLC tumor specimens and in the in vitro data, supporting the role of c-kit in autocrine and paracrine growth stimulation specifically in SCLC. Unfortunately, no responses were observed, and all patients had disease progression by Week 4 in their study. The authors explained the lack of activity for imatinib in the patient population by the absence of activating c-kit mutations in SCLC. We want to mention another possible explanation.

In their study, despite the fact that imatinib was used in patients with recurrent SCLC, c-kit status was evaluated in primary tumors. The tumor cells are changing constantly and continue to mutate at a rapid rate during progression of the disease.2 In addition, chemotherapy that was initiated up-front for these patients also may have changed the signal-transduction pathways associated with tumor growth. All of these factors may cause a discrepancy in c-kit status between primary and metastatic SCLC in the same patient that may explain further the lack of activity for imatinib in this patient population.