Osimertinib for Patients With Progressive EGFR-Mutated T790M-Negative NSCLC

According to results from a phase 2 study published in Lung Cancer, osimertinib demonstrated modest antitumor activity in patients with epidermal growth factor receptor (EGFR)-mutated T790M-negative non-small cell lung cancer (NSCLC) that has progressed after treatment with first- or second-generation tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy.

Masayuki Takeda, MD, PhD, Kindai University, Osaka, Japan and coauthors explained that among patients with both EFGR and T7990M mutations who develop treatment resistance, “only approximately half have a chance to receive subsequent osimertinib treatment,” due to the fact that, “osimertinib is not indicated for patients without T790M mutations in clinical practice.”

The phase 2 study enrolled 55 patients from 15 institutions from August 2020 to February 2021, with response rate as the primary end point. After a median follow-up time of 13.2 months (0.4 to 17.9 months), overall response rate (ORR) was 29.1% (95% confidence interval [CI], 17.6 to 42.9). Progressive disease was observed in 32.7% (18) of patients, with stable disease found in 16 (29.1%) patients. Median progression-free survival (PFS) was 4.07 months (95% CI, 2.1 to 4.3) with a 12-month PFS rate of 17.3%.

Adverse events (AEs) occurred in 92.7% (51) of patients. Grade >3 AEs occurred in 32.7% (18) of patients. The most common AEs included diarrhea (32.7 %), acneiform eruption (16.4 %), rash (20.0 %), and paronychia (27.3 %). No treatment-related deaths were reported.

The study authors concluded that “our results suggest that osimertinib is a treatment option for patients with metastatic NSCLC that is negative for the EGFR T790M mutation and has progressed during or after first- or second-generation EGFR TKI therapy.

“Further investigation of biomarkers to predict osimertinib efficacy in such patients is warranted,” they added.

Source:

Takeda M, Shimokawa M, Nakamura A, et al. A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. Lung Cancer. 2023;177:44-50. doi:10.1016/j.lungcan.2023.01.011