154P CNS response to osimertinib in patients with EGFR mutated lung adenocarcinoma: Real world data

Devjak, Rok; Hitij, Nina Turnsek; Mohorcic, Katja; Rajer, Mirjana; Čufer, Tanja

doi:10.1016/s1556-0864(18)30428-3

Cited by 3 publications

(14 citation statements)

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“…The second outlier study 24 reported a CNS ORR of 91% (95% CI, 71%-99%; 20 of 22 patients). This percentage may be higher than the value reported herein because the patients in that study had not received any previous EGFR-TKI treatment, in contrast to the patients in many of the included studies 19,23,31,33,34,36,[38][39][40] who received osimertinib as second-line or third-line therapy.…”

Section: Discussion Effectivenessmentioning

confidence: 56%

“…Meta-analyses of proportions generated summary estimates for CNS ORR 19,23,24,31,33,34,36,[38][39][40] of 64% (95% CI, 53%-76%; n = 195) ( Figure 2) and for CNS DCR 19,23,24,31,[34][35][36]39,41 Downloaded From: https://jamanetwork.com/ on 10/11/2020 85%-93%; n = 246) ( Figure 3). [25][26][27] Results of statistical tests indicated high heterogeneity for CNS ORR (I 2 = 77%, 95% CI, 58%-88%; τ 2 = 0.0268, 95% CI, 0.0054-0.0938; Q = 39.29, P < .001) and low heterogeneity for CNS DCR (I 2 = 0%, 95% CI, 0%-58%; τ 2 = 0, 95% CI, 0-1.25; Q = 6.67, P = .57).…”

Section: Cns Orr and Cns Dcrmentioning

confidence: 99%

“…Table 2 summarizes extracted outcome data in the 15 studies. 19,23,24,[30][31][32][33][34][35][36][37][38][39][40][41]…”

Section: Other Effectiveness Outcomesmentioning

confidence: 99%

“…Of the 15 included studies, 19,23,24,[30][31][32][33][34][35][36][37][38][39][40][41] safety outcomes were reported in 7 studies. 19,23,24,34,[37][38][39] In their retrospective study of 40 patients with IMD receiving osimertinib, Xie et al 38 only in the study of 22 patients receiving osimertinib by Xing et al, 39 with 1 patient experiencing CTCAE grade 3 fatigue and more patients experiencing CTCAE grade 1 or 2 adverse events (7 with fatigue, 4 with nausea, 3 with vomiting, 2 with headache, and 3 with dizziness).…”

Section: Safetymentioning

confidence: 99%

“…Six studies 19,23,24,31,32,34 reported pharmaceutical industry funding. Overall, 6 studies 19,23,32,37,38,40 were at high risk of bias in 1 criterion, and 3 studies 30,31,34 were at high risk of bias in 2 criteria.…”

Section: Assessment Of Study Qualitymentioning

confidence: 99%

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Assessment of Effectiveness and Safety of Osimertinib for Patients With Intracranial Metastatic Disease

2020

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IMPORTANCE Intracranial metastatic disease (IMD) is a serious and life-altering complication for many patients with cancer. Targeted therapy may address the limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Given the paucity of evidence regarding effectiveness, current guidelines have not made recommendations on the use of targeted therapy. Osimertinib mesylate is a mutant epidermal growth factor receptor (EGFR) inhibitor that can penetrate the blood-brain barrier and inhibit tumor cell survival and proliferation in patients with non-small cell lung cancer (NSCLC) with specific EGFR alterations. OBJECTIVE To assess the effectiveness and safety of osimertinib in the management of IMD. DATA SOURCES Studies were selected from MEDLINE and Embase databases from their inception to September 20, 2019, using the following search query: (osimertinib OR mereletinib OR tagrisso OR tamarix OR azd9291) AND (brain metastases OR intracranial metastatic disease OR cns). STUDY SELECTION Studies reporting intracranial outcomes for patients with metastatic EGFRvariant NSCLC and IMD treated with osimertinib were included in this systematic review and metaanalysis. Among 271 records identified in the systematic review, 15 studies fulfilled eligibility criteria for inclusion in the meta-analysis. DATA EXTRACTION AND SYNTHESIS Data were extracted from published studies and supplements. These data were pooled using a random-effects model. Risk of bias was assessed using the Cochrane risk of bias tool and the modified Newcastle-Ottawa Scale. MAIN OUTCOMES AND MEASURES Information extracted included study characteristics, intracranial effectiveness measures, and safety measures. Meta-analyses of proportions were conducted to pool estimates for central nervous system (CNS) objective response rate and CNS disease control rate. RESULTS Fifteen studies reporting on 324 patients were included in the meta-analysis. The CNS objective response rate was 64% (95% CI, 53%-76%; n = 195), and CNS disease control rate was 90% (95% CI, 85%-93%; n = 246). Included studies reported complete intracranial response rates of 7% to 23%, median best decrease in intracranial lesion size of −40% to −64%, and Common Terminology Criteria for Adverse Events (version 3.0) grade 3 or higher adverse event rates of 19% to 39%. Subgroup analyses did not reveal additional sources of heterogeneity. CONCLUSIONS AND RELEVANCE Findings reported herein support a potential role for osimertinib in the treatment of patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib.

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