First-line osimertinib, a targeted therapy against EGFR mutations, was found to be effective in patients with advanced non–small-cell lung cancer (NSCLC), resulting in a 77% overall response rate, according to the results of recent study. In addition, the treatment-naive patients in the study achieved a median progression-free survival of 19.3 months.
The data from two phase I expansion cohorts were presented by Suresh Ramalingam, MD, professor of hematology and medical oncology at Emory School of Medicine and deputy director of the Winship Cancer Institute in Atlanta, at the European Lung Cancer Conference 2016 in Geneva (LBA 1_PR).
“The overall response rate was among the best reported for first-line therapy of EGFR-mutated NSCLC,” Ramalingam said in a press release. “The progression-free survival results are exciting, well exceeding the historical control rates of 10 to 13 months with first- or second-generation drugs. Many of the patients have not had disease progression on the study and are still benefitting from treatment.”
The study included 60 patients with locally advanced or metastatic NSCLC. Patients were assigned to either 80 mg or 160 mg osimertinib once daily. The median follow-up was 16.6 months.
The overall objective response rate was 77%. Patients given the 80-mg dose had a response rate of 67% and patients given the higher dose had a response rate of 87%. In the 160-mg dose group the median progression-free survival was 19.3 months, but it was not yet reached in patients given the 80-mg dose. At 18 months, 55% of the cohort was free from progression.
Only 10% of patients at the 80-mg dose required a dose reduction due to adverse events, the most common of which were diarrhea, stomatitis, and paronychia.
Initial data suggests that patients who had disease progression did not have a T790M mutation as the mechanism of resistance. “That tells us that we may be changing the biology of the disease with the use of first-line osimertinib,” Ramalingam said.
A second abstract (LBA2_PR) was also presented, detailing updated results of phase I and pooled phase II trials of 80-mg osimertinib in pretreated patients with T790M-positive advanced NSCLC.
Response rates were 71% in the phase I dose expansion cohort of 63 patients and 66% in pooled results from two phase II studies of 411 patients. Progression-free survival was 9.7 and 11 months for the phase I cohort and phase II studies, respectively.
“We found a response rate and progression-free survival that were consistent between the two studies and with earlier reports from the AURA studies,” said lead author James Yang, MD, PhD, director of the department of oncology and department of medical research, National Taiwan University Hospital, Taipei, Taiwan, in a press release. “Adverse events such as interstitial lung disease and QT prolongation were infrequent, with similar rates to our previous analyses.”
He concluded: “In this mature pooled analysis for T790M-positive EGFR mutant patients who have progressed on a prior EGFR tyrosine kinase inhibitor (TKI), we were able to show a high overall response rate, encouraging duration of response and good tolerability profile. Progression-free survival was long compared to the 4 to 5 months provided by chemotherapy. This is good news for patients with EGFR mutations who have failed [on an] EGFR TKI, for whom osimertinib is now standard of care. Molecular diagnosis for T790M must now be the standard as well.”