FLAURA trial: My Perspective on First Line EGFR Mutation-Positive NSCLC Today

There was certainly not enough cross-over to osimertinib on the "standard of care" arm to answer that question. Are you proposing that cross-over to osimertinib be regardless of T790M? The results with osimertinib in T790M-negative acquired resistance have been poor enough that I am inclined to accept a 9 month difference in median PFS. In the second-line setting, the PFS with osimertinib has been in the 9 month range just for those with T790M, but it appears to be more like 2-3 months in the 40-50% who have T790M-negative acquired resistance. Frankly, with the FLAURA results showing better efficacy and tolerability, and with far better CNS activity with osimertinib, I don't think another trial asking the question a different way should be a high priority. It is all but inconceivable that first line osimertinib will be worse, and the only reason to persist with a first generation EGFR TKI is because of the lower cost. That is not unreasonable, but I don't think it's a compelling reason to run another trial.

We need a trial comparing survival with gefitinib or erlotinib in first line followed by osimertinib in second line versus osimertinib in first line alone. This study decides if osimertinib would be the new standard of care for patients with EGFR-mutated NSCLC. The Flaura study does not answer this question.