Nationwide Molecular Profiling ‘Feasible’ For Advanced NSCLC

Nationwide profiling of six molecular alterations has been successfully conducted in French advanced non-small-cell lung cancer patients

medwireNews: The results of a 1-year study suggest that nationwide screening for key molecular alterations is feasible in patients with advanced non-small-cell lung cancer (NSCLC), with improved survival found in some patients with targetable Mutations.

The French National Cancer Institute programme included 18,679 molecular investigations of 17,664 advanced NSCLC patients who were screened for six different oncogenic drivers between 2012 and 2013.

Test results were available after a median of 11 days, showing that Molecular profiling on a nationwide scale “is feasible with an acceptable turnaround”, say Fabrice Barlesi, from Aix Marseille University in France, and co-workers.

Moreover, patients with a genetic alteration had a significant 4.7-month increase in overall survival compared with those without, indicating “a possible prognostic advantage or a major change in the management of these patients with advanced NSCLC, or both”, they write.

Half of the screened patients tested positive for at least one genetic alteration, with available data indicating EGFRmutations in 11%, HER2mutations in 1% and KRASmutations in 29%.

In addition, BRAF and PIK3CAmutations were each detected in 2% of patients and ALKrearrangements in 5%, the team reports in The Lancet.

Genetic alterations influenced first-line advanced NSCLC treatment decisions in 51% of 8147 patients and these individuals were followed-up for a median of 24.9 months.

Overall response to both first-line and second-line treatment was significantly more common in patients with a genetic alteration than those without, at 37% versus 33%, and 17% versus 9%, respectively.

Patients with a genetic alteration also experienced significantly longer first-line progression-free survival (median, 10.0 vs 7.1 months) and overall survival (16.5 vs 11.8 months) than those without a targetable mutation.

Multivariate analysis confirmed that the presence of ALK, EGFR and HER2alterations were significantly associated with improved prognosis, with hazard ratios of 0.70, 0.53 and 0.60, respectively.

The researchers admit that the improvement in survival for patients with actionable targets came at “a non-negligible financial cost” and note that the programme failed to improve the rate of inclusion in clinical trials for patients with molecular alterations that are targeted only by experimental compounds.

Nevertheless, they conclude: “[O]ur results should encourage all continuing worldwide initiatives to provide patients with cancer with access to personalised treatment, and provide robust information to inform these initiatives.”

Reference

Barlesi F, Mazieres J, Merlio J-P, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016; Advance online publication 14 January. DOI: http://dx.doi.org/10.1016/S0140-6736(16)00004-0

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