Yang Yang and colleagues from the Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Province, China carried out the study to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment.
Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). The co-primary endpoints were overall survival (OS) and progression-free survival (PFS).
The interesting findings revealed that-
- After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39–0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1–14.8] for OSI vs 9.6 months [95% CI, 8.4–10.2] for AFA).
- The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41–0.91; p = 0.014; median, 4.5 months [95% CI, 3.5–5.7] vs 3.9 months [95% CI, 3.1–4.8]).
- The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%).
Therefore, the authors concluded that "noteworthy survival superiority of OSI over AFA was observed in patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment."
AFA is a broad HER-family inhibitor, whereas OSI is a highly specific EGFR-inhibitor directed towards the sensitizing mutations and a potent inhibitor of the T790M mutation. The latter is probably most important in this resistance setting, along with the better CNS-penetrance, they further added.
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