More than 40% of non-small cell lung cancer (NSCLC) patients develop CNS metastasis in their lifetime. Clinical studies have shown superior efficacy of osimertinib in CNS compared to platinum chemotherapy. Treatment efficacy in patients with or without CNS metastasis were observed within the second interim analysis of ASTRIS (NCT02474355). Data cut-off (DCO) was 20 October 2017.
In ASTRIS, advanced NSCLC patients with locally confirmed T790M mutation, prior EGFR-TKI therapy were enrolled. Patients with stable CNS metastases were allowed. The primary endpoint was overall survival (OS); other endpoints included investigator-assessed response rate (RR), progression-free survival (PFS), time to treatment discontinuation (TTD) and safety. These endpoints were also analyzed according to presence of CNS metastasis.
In 466 Korean patients, CNS metastasis was evaluated in 310 patients and was present in 211 (68.1%) patients (CNS-met) and not present in 99 (31.9%) patients (CNS-no). 155 patients were not evaluated for CNS metastasis (CNS-ne). At DCO, 236 patients (50.6%) were ongoing and median duration of exposure was 11.2 (0–19) months. In patients evaluable for response, defined as at least one dose of osimertinib and one response assessment, RR was 71.0% (320/451; 95% CI, 66.5–75.1): Patients with (N = 211), without (N = 99), and not-evaluated CNS metastasis (N = 155) had RR of 68% (134/197), 79.6% (78/98), and 69.7% (108/155), respectively. Median PFS was 12.4 months (95% CI, 11.1-13.6); 10.8 months in CNS-met, 11.0 months in CNS-no, and 15.1 months in CNS-ne. Median TTD was 16.5 months (95% CI, 14.1-NC); 11.2 months in CNS-met, 14.7 months in CNS-no, and NC (95% CI, 15.5-NC) in CNS-ne. OS was not reached (data maturity: 19.7%). Serious adverse events (AE) regardless of causality were reported in 116 patients (24.9%) and AEs leading to death in 13 patients (2.8%). ILD/pneumonitis-like events were reported in 8 patients (1.7%), and QTc prolongation in 7 patients (1.5%).
In the ASTRIS Korean subset, patients with or without CNS metastasis had comparable efficacy outcomes. These data continue to support osimertinib’s clinical benefit on EGFRm T790M NSCLC patients with CNS metastasis.
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All authors have declared no conflicts of interest.