• In the Phase I/II (n = 130) TIGER-X trial of rociletinib for patients with acquired resistance to first- or second-generation TKIs, the ORR was 59% among patients with the T790M mutation and 29% among those without it.
• T790M plasma testing is a viable alternative to tissue testing ​
(ORR = 57% among patients with T790M-positive disease using this method).

Rociletinib is another third-generation EGFR TKI that seems poised to soon enter practice, and like osimertinib (AZD9291), it seems likely that the initial indication will be for patients with disease progression on a first- or second-generation EGFR TKI with a T790M mutation. Ongoing trials are evaluating both agents in the first-line setting.

An unexpected but noteworthy problem that has thus far proven unique to rociletinib is Grade 3 hyperglycemia, which has been observed in up to 22% of patients but is reported to be easily controlled in most cases with metformin or dose reduction. The pathophysiology of this complication is the inhibition of the insulin growth factor receptor 1 and the insulin receptor by a metabolite of rociletinib called M502, and it is thought that insulin will have no benefit in these patients. Despite this complication, rociletinib, like osimertinib, is advantageous in that it does not target wild-type EGFR, resulting in less severe rash and diarrhea.