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Abstract 1642: Alectinib in treatment-naïve anaplastic lymphoma kinase-positive (ALK+) metastatic non-small-cell lung cancer (mNSCLC): Systematic literature review (SLR) and network meta-analysis (NMA)

Background: The standard of care for treatment-naive ALK+ mNSCLC patients (pts) is an ALK tyrosine kinase inhibitor (TKI). Pts treated with crizotinib generally experience disease progression within 1 year, often within the central nervous system (CNS). As such, there is a high unmet need for CNS-active ALK TKIs. Phase III data from 2 ALK TKIs, alectinib and ceritinib, showed improved efficacy vs crizotinib and chemotherapy, respectively; however, no studies have directly compared these TKIs. We report a NMA to compare the efficacy/safety of these therapies. Methods: A SLR was conducted to identify ALK+ mNSCLC randomized controlled trials (RCTs) in treatment-naive pts. Efficacy/safety endpoints were extracted and the feasibility of using the data in a NMA was assessed. Data were analyzed using a fixed effect analysis in WinBUGs following NICE guidelines. Results: 1194 citations were identified, of which 4 RCTs were in treatment-naive pts (ALEX [NCT02075840], ASCEND-4 [NCT01828099], PROFILE 1014 [NCT01154140] and PROFILE 1029 [NCT01639001]). All were open-label, phase III RCTs and pts were similar in terms of age, ECOG PS, disease stage, sex and smoking status. More pts had baseline CNS metastasis (mets) in ALEX (40%) vs the other trials (26-32%). PROFILE 1029 was conducted in East Asian pts and only included in a sensitivity analysis. Chemotherapy arms differed in that pemetrexed maintenance was included in ASCEND-4 but not in the PROFILE studies. Key efficacy/safety results are shown in the Table. Data from the sensitivity analyses were similar. Conclusion: Alectinib significantly improved progression-free survival compared with other treatments in the ITT population including in pts with baseline CNS mets. Alectinib showed significantly fewer grade 3-4 AEs than ceritinib. The difference in chemotherapy arms of the 2 trials may have impacted the NMA efficacy results. Citation Format: Anna Steenrod, Michelle Orme, Katherine S. MacGilchrist, Rachel Rosenthal, Juliane Schaefer, Vlatka Smoljanovic, Emmanuel Mitry, Parneet K. Cheema. Alectinib in treatment-naive anaplastic lymphoma kinase-positive ( ALK +) metastatic non-small-cell lung cancer (mNSCLC): Systematic literature review (SLR) and network meta-analysis (NMA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1642.