Rociletinib for EGFR-mutated Non–Small-Cell Lung Cancer

In patients with non–small-cell lung cancer (NSCLC), resistance to first-generation epidermal

growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is usually mediated by the T790M EGFR gene mutation. Rociletinib is an oral EGFR mutant-selective inhibitor that has demonstrated activity against EGFR-mutated NSCLC with or without T790M mutation.

Investigators have now conducted an industry-supported, phase 1–2 dose-escalation and expansion trial of rociletinib in patients with EGFR-mutated NSCLC who acquired resistance to EGFR TKIs; the expansion segment of the study (phase 2) involved patients with confirmed T790M-positive disease. Of 130 patients, 38 received free-base rociletinib at a dose of <900 mg twice daily, which was considered subtherapeutic. The following results were reported for the remaining 92 patients who received ≥900 mg twice daily of free-base rociletinib or any dose of the hydrogen bromide form of rociletinib:

• The maximum tolerated dose was not reached. The main dose-limiting toxicity was grade 3 hyperglycemia, which occurred in 22% of patients; another 5% experienced grade 3 QTc prolongation, but all were managed with dose-reductions.

• Among 46 patients with centrally confirmed T790M-positive disease, the response rate was 59%, the disease-control rate was 93%, and the median progression-free survival (PFS) was 13.1 months.

• Among 17 patients with centrally confirmed T790M-negative disease, the response rate was 29%, the disease-control rate was 59%, and the median PFS was 5.6 months.