Co-Occurrence of ALK Rearrangement and KRAS G12C Mutation in NSCLC: Report of Two Cases

In the last few years, non-small cell lung cancer (NSCLC) treatment has totally revolutionized by the improvement in molecular diagnostics and the introduction of targeted therapies, becoming the standard of care in patients with actionable alterations. Mostly, genomic mutations are mutually exclusive although some cases of co-occurring actionable alterations could be discovered, especially with the recent introduction of genomic sequencing by next generation sequencing (NGS). Few data are available in the treatment of these particular cases. The co-occurring RAS G12C mutation seems to be a poor prognostic factor in patients with ALK rearranged NSCLC. We report two cases of women with diagnosis of advanced adenocarcinoma oncogene addicted with ALK rearrangement and KRAS G12C mutation. In both cases the PD-L1 status was high (>50%). Although both received Alectinib as ALK inhibitor, the lesion rapidly progressed. The patients had benefit only by treatments with chemotherapy, while anti PD-1/PD-L1 axis inhibitors seemed to be inefficient. Precise diagnostic techniques allow the detection of concomitant driver alterations; therefore, oncologists should consider these rare double mutations in NSCLC patients. Further prospective study is still warranted to investigate the role of co-occurring driver alterations and the relevant treatment paradigm