Blood Samples as Surrogates for Tumor Biopsies in Patients with Lung Cancer

“A study examined the feasibility of using circulating free DNA (cfDNA) from blood samples of patients with advanced non-small-cell lung cancer as a surrogate for tumor biopsies to determine tumor-causing epidermal growth factor receptor (EGFR) mutations and then correlate that with expected patient outcomes, according to a study published online by JAMA Oncology.

“The analysis was a secondary objective of the EURTAC trial, which demonstrated the efficacy of erlotinib compared with standard chemotherapy for the first-line treatment of European patients with advanced non-small-cell lung cancer (NSCLC) with oncogenic EGFR mutations (exon 19 deletion or L858R mutations in exon 21) in tumor tissue.

“Rafael Rosell, M.D., of the Hospital Germans Trias I Pujol, Badalona, Spain, and coauthors examined EGFR mutations in cfDNA isolated from 97 baseline blood samples.

“Results show that in 76 samples from 97 (78 percent) patients, EGFR mutations in cfDNA were detected. Median overall survival was shorter in patients with the L858R mutation in cfDNA than in those with the exon 19 deletion (13.7 vs. 30 months). For patients with the L858R mutation in tissue, median overall survival was 13.7 months for patients with the L858R mutation in cfDNA and 27.7 months for those in whom the mutation was not detected in cfDNA. For the 76 patients with EGFR mutations in cfDNA, only erlotinib treatment was an independent predictor of longer disease progression-free survival.”

Direct Drug Screening of Patient Biopsies Could Overcome Resistance to Targeted Therapy

The gist: Scientists are working on using individual patients’ cancer cells in the lab to figure out whether different treatments might work best for each patient. It is hoped that the approach would help patients get around the problem of treatment resistance. The research is cutting-edge, so it is not yet something that could be done for most patients.

“A new screening platform using cells grown directly from tumor biopsy samples may lead to truly individualized treatment strategies that would get around the problem of treatment resistance, which limits the effectiveness of current targeted therapy drugs. In a paper that will appear in Science and is receiving advance release on the Science Express website, researchers from the Massachusetts General Hospital (MGH) Cancer Center describe how screening samples grown from treatment-resistant tumors against a panel of current and potential targeted therapy drugs identified previously unknown resistance mechanisms, several of which could not be found by gene sequencing.

” ‘Genetics has been extremely useful to guiding treatment, but in many cases tumor genetics are ambiguous or do not reveal a mutation that informs a therapeutic strategy,’ says Jeffrey Engelman, MD, PhD, co-senior author of the report. ‘These functional pharmacologic studies can identify effective therapeutic choices even when the genetics fail to do so.’

“While the use of drugs that target genetic changes driving tumor growth induces remissions and gives many patients significant symptom relief, in almost all cases the effects are temporary because resistance appears in a year or two. Resistance develops either through secondary mutations that block the original drug’s action on the target molecule or through activation of a secondary pathway to carry molecular signals that sustain tumor growth. Previous efforts to study resistance mechanisms – either by inducing resistance in the laboratory using established cell lines or by looking for new mutations in resistant tumor cells – have significant limitations.”