AZD9291 and rociletinib – another ray of hope for patients with progressive EGFR mutation-positive NSCLC Two studies published concurrently in the New England Journal of Medicine (N Engl J M) on April 30 published data on rociletinib (Clovis Oncology) and AZD9291 (AstraZeneca) for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), respectively, unveiling data on third-generation EGFR inhibitors for the treatment of NSCLC. Due to the advent of EGFR T790M, patients with EGFR(+) NSCLC became resistant to first-generation EGFR inhibitors (e.g., erlotinib, gefitinib) and second-generation EGFR inhibitors (e.g., afatinib). said Dr. Pasi J?nne of the Dana-Farber Cancer Institute, USA, principal investigator of the AZD9291 clinical trial. “When patients progress after treatment with EGFR inhibitors, we don’t know what to do next, and now for these patients, we have a new treatment strategy.” The efficacy of AZD9291 and rociletinib was similar. Subgroup analysis showed that those with progressive disease in the presence of the T790M mutation had response rates of around 60% for both drugs, with a median progression-free survival (PFS) period of 10 months. The difference between the two is that AZD9291 is given orally once daily, while rociletinib is given twice daily, and rociletinib has a side effect of elevated blood sugar, which was not observed in the AZD9291 study. Its skin toxicity and the diarrhea it causes were both reduced. “Initially, this was seen in the higher AZD9291 dose group (skin toxicity reactions), but we did not observe it at doses of 80 mg once daily, so this should be a future dose option. Previous generations of EGFR inhibitors caused diarrhea and patients had to be treated with antidiarrheal therapy, especially those on afatinib and sometimes with erlotinib (diarrhea), which did not occur in AZD9291 takers.” AZD9291 was recently designated by the FDA as a “fast-track” drug and is expected to be approved by the end of this year for patients with T790M mutations whose disease has progressed after treatment with EGFR inhibitors. Currently, detection of T790M mutations relies on biopsy of tumor tissue specimens, but perhaps in the future, we will be able to obtain this information from circulating tumor cell DNA in blood or urine.