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OA02 - A New Vision of Targets and Strategies (ID 120)
- Event: WCLC 2019
- Type: Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
OA02.07 - Phase 3 ALUR Study of Alectinib in Pretreated ALK+ NSCLC: Final Efficacy, Safety and Targeted Genomic Sequencing Analyses (Now Available) (ID 2267)
10:30 - 12:00 | Author(s): Thorsten Ruf
The ALUR (NCT02604342) primary analysis (cut-off January 2017) demonstrated improved efficacy and safety with alectinib versus chemotherapy in patients with ALK+ NSCLC previously treated with chemotherapy and crizotinib. These patients can develop crizotinib resistance through ALK secondary mutations, but limited data exist regarding alectinib’s efficacy in patients with different post-crizotinib genetic profiles. We report final data from ALUR including treatment outcomes according to genetic profile.Method
Overall, 119 patients with locally determined ALK+ NSCLC were randomised 2:1 to receive alectinib 600mg bid or chemotherapy (pemetrexed 500mg/m2 or docetaxel 75mg/m2 q3w). The primary endpoint was PFS by investigator. Targeted genomic sequencing (FoundationONE® [tissue; 315 genes] and FoundationACT® [plasma; 62 genes]) was performed retrospectively using tumour tissue (n=33) and baseline plasma (n=59).Result
Final efficacy data confirmed those of the primary analysis (table). Grade ≥3 treatment-emergent adverse events were lower with alectinib (37.7%) than with chemotherapy (43.2%); adverse events causing treatment discontinuation were lower with alectinib (5.2% versus 10.8% chemotherapy), despite alectinib’s longer treatment duration. ALK fusions were confirmed retrospectively in 26/33 (78.8%) tissue and 41/59 (69.5%) plasma (post-crizotinib) samples. ORR in alectinib-treated patients with ALK fusions was 72.2% (13/18, tissue) and 63.0% (17/27, plasma) versus 0% for chemotherapy (tissue [0/8], plasma [0/14]). ALK secondary mutations were detected in 16/59 (27.1%) patients (plasma, both arms). ORR in the alectinib arm (plasma) was similar in patients with ALK fusions with (60.0%, 6/10) or without (64.7%, 11/17) ALK secondary mutations, but lower in patients with gene mutations other than ALK (23.1%, 3/13).Conclusion
Final data from ALUR confirm the primary analysis, demonstrating improved efficacy and safety with alectinib versus chemotherapy in post-crizotinib ALK+ NSCLC. The role of reconfirming ALK status upon sequential ALK inhibitor treatment requires further investigation, due to the limited data and known technical challenges of plasma testing.
Funding: F. Hoffmann-La Roche Ltd.
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