Commenting on the study by Jänne et al, ASCO President Peter P. Yu, MD, said that the issue of drug resistance is important to understand for all cancers, but it is difficult to overcome resistance.

“This clinical trial has important implications not only for NSCLC patients but for all patients treated with targeted therapy who subsequently develop drug resistance. In this phase I study, the investigators were able to demonstrate that precise knowledge about the mechanism of acquired drug resistance directly led to the design of a third-generation EGFR-targeted therapy to overcome this resistance. In addition, the greater precision appears to have reduced the toxicity rendered to normal tissues that presumably do not express this mutation,” Dr. Yu told The ASCO Post.

“Like any good study,” he continued, “this study raises interesting questions that will be addressed in phase II and III trials to follow. Since about 25% of patients who did not harbor the targeted mutation responded to therapy, it raises the question of whether this drug may have a role in first-line therapy of EGFR-mutated lung cancer, either because of reduced toxicity or more durable responses. Alternatively, it may be best to reserve this drug to treat acquired resistance if the initial tumor at presentation did not have the targeted T790M mutation.” ■

Disclosure: Dr. Yu reported no potential conflicts of interest.