by ecancer reporter Janet Fricker

Broad genotype screening using 'SNaPshot technology' to guide therapy in non small-cell lung cancer (NSCLC) patients has for the first time been shown to be effective in the clinic, reports a study in Annals of Oncology. By identifying patients' individual genotypes within a relatively short time frame, 'SNaPshot' allowed doctors to target tumours with the most appropriate therapy.

In NSCLC it is recognised that determining genotype can inform the most effective personalised therapy, with patients with epidermal growth factor receptors (EGFR) genes benefiting from EGFR tyrosine kinase inhibitors (TKIs) and patients with ALK translocations benefitting from crizotinib. Choosing the right therapy raises the response rates in NSCLC patients from around 20-30% to 60-75%, with the potential to improve survival.

SNaPshot is a multiplexed PCR-based assay - developed by the study investigators led by Dora Dias-Santagata from the Massachusetts General Hospital Cancer Center, Boston USA - which amplifies multiple mutation sites in different genes in a single polymerase chain reaction (PRC). The technology, which saves considerable time and effort, was designed to test 50 hot-spot mutation sites in 14 key cancer genes. Between March 2009 and May 2010 samples from 589 NSCLC patients were analysed using SNaPshot, with 546 patients having enough tissue for the full analysis.

Results, which had an average turnaround time of 2.8 weeks, show that one or more mutations were found in 51% (282) of the samples, with the most common being in the KRAS (24%), EGFR (13%), ALK (5%), TP53 (5%) and PIK3CA (4%) genes. Additionally the investigators identified over 30 patients with less common mutations like BRAF, PIK3CA and HER2, which also have relevant candidate targeted therapies. Among the patients with advanced or recurrent NSCLC, 22% began a genotype-specific therapy in response to SNaPshot results.

"In our experience, SNaPshot tumor genotyping is a viable clinically feasible approach to support diagnostic and treatment decisions and to facilitate clinical trial enrolment. It is uncovering new therapeutic opportunities for a growing number of patients and advancing NSCLC management," write the authors.

The technology, they add, has since been extended to a range of solid tumour such as colorectal, breast and gliomas.

Reference

LV Sequist, RS Heist, AT Shaw et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice, Annals of Oncology, 2011, 22: 2616–2624., doi:10.1093/annonc/mdr489