FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Rociletinib, a third-generation EGFR tyrosine kinase inhibitor that targets mutations causing treatment resistance, showed sustained activity against resistant non–small cell lung cancer (NSCLC) in a phase I clinical trial, according to a report published online April 30 in the New England Journal of Medicine.
The study, sponsored by Clovis Oncology, the maker of rociletinib, involved 130 patients enrolled over the course of 2 years at 10 medical centers in the United States, France, and Australia. All the study participants had received at least one first- or second-generation EGFR inhibitor (usually erlotinib), and their NSCLC tumors had mutated and developed resistance to the therapy. Half of these patients had three or more sites of metastasis, and 44% had brain involvement, said Dr. Lecia V. Sequist of the deparment of medicine, Massachusetts General Hospital, Boston, and her associates.
A total of 92 patients received therapeutic doses of rociletinib. After a median follow-up of 10 weeks, the response rate among the 46 whose cancer had known EGFR T790M mutations was 59%; 43 of these 46 patients achieved a partial response, a complete response, or disease stabilization. As expected, the response rate was lower, at 29%, among the 17 patients whose tumors were T790M negative, the investigators reported (New Engl. J. Med. 2015 April 30 [ doi:10.1056/NEJMoa1413654 ]).
“Rociletinib did not cause the syndrome of rash, stomatitis, and paronychia that is associated with inhibition of nonmutant EGFR,” they wrote, and the most common grade 3 toxic effect was hyperglycemia. No hyperglycemic events led to discontinuation of treatment, and most were managed with a dose reduction plus use of an oral hypoglycemic agent, usually metformin. Both the hyperglycemia and the metformin may have contributed to gastrointestinal adverse events, which were generally mild.
The main limitation of this study is the small number of patients who have received rociletinib. Larger studies of the agent are now underway, Dr. Sequist and her associates said.
This study was funded by Clovis Oncology, maker of rociletinib, which also participated in study design and data collection and analysis. Dr. Sequist reported receiving personal fees from, and consulting for, Clovis Oncology, AstraZeneca, Boehringer Ingelheim, Novartis, Genentech, Merrimack, and Taiho, and her associates reported ties to numerous industry sources.
