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March 2016

Postprogression Prolongation of Survival in EGFR-Mutated Lung Cancer: Reconciling the ASPIRATION and IMPRESS Trials

Author Affiliations
  • 1UC Davis Comprehensive Cancer Center, Sacramento, California
  • 2Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 3University of Colorado Cancer Center, Aurora
JAMA Oncol. 2016;2(3):300-301. doi:10.1001/jamaoncol.2015.4920

The advent of targeted therapy with tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) in EGFR-mutated lung cancers has led to dramatic improvements in response and progression-free survival (PFS). Nevertheless, essentially all initially responding patients eventually develop acquired resistance and die from this neoplasm. What to do at the time of documented progressive disease (PD) continues to be a controversial subject, as demonstrated by the article by Park et al1 in this issue of JAMA Oncology. In 2015, options when PD is documented include (1) a switch to platinum-based chemotherapy; (2) a switch to a third-generation TKI therapy in those patients found to have the resistance mutation T790M at rebiopsy. Or (3) continuing the initial TKI alone or (4) in combination with chemotherapy. The article by Park et al1 adds to the available literature on this subject and also to the confusion about what the right approach is. The Conclusions and Relevance paragraph in the abstract includes the statement “treatment beyond progression is feasible and may delay salvage therapy in selected patients.” This indeed is the crux of the matter. What advantages are there to “delaying salvage therapy,” and who are the “selected patients”?