Final, mature progression-free survival ( PFS ) from the global phase III ALEX study of Alectinib ( Alecensa ) vs Crizotinib ( Xalkori ) in untreated, advanced / metastatic anaplastic lymphoma kinase-positive non-small-cell lung carcinoma ( ALK+ NSCLC ) have been previously published: Alectinib 34.8 months ( 95% CI, 17.7–NR [ non-reached ] ) versus Crizotinib 10.9 months ( 95% CI 9.1–12.9 ), ( hazard ratio, HR 0.43, 95% CI 0.32–0.58 ).
Researchers have reported 5-year overall survival ( OS ) and updated safety data from ALEX trial with a further 12 months follow-up ( cutoff date: November 29, 2019 ).
Patients with stage IIIB/IV ALK+ NSCLC ( by central IHC ), ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC were randomized 1:1 to Alectinib 600 mg BID ( n = 152 ) or Crizotinib 250 mg BID ( n = 151 ).
Asymptomatic CNS metastases at baseline were allowed. Overall survival was a secondary endpoint, and no formal statistical testing was planned.
Median duration of follow-up was: 48.2 months with Alectinib vs 23.3 m with Crizotinib.
OS data remained immature ( events: 37%; stratified HR 0.67 [ 95% CI 0.46–0.98 ] ); median overall survival with Crizotinib was 57.4 months ( 95% CI 34.6–not estimable [ NE ] ) versus NE with Alectinib.
The 5-year survival rate was 62.5% ( 95% CI 54.3–70.8 ) with Alectinib versus 45.5% ( 95% CI 33.6–57.4 ) with Crizotinib.
In patients with CNS metastases at baseline the OS HR was 0.58 ( 95% CI 0.34–1.00 ) and 0.76 ( 95% CI 0.45–1.26 ) in patients without CNS metastases at baseline.
The OS benefit of Alectinib vs Crizotinib was generally consistent across all subgroups.
Considering the longer treatment duration for Alectinib ( 28.1 months ) versus the previous analysis ( 27.7 months ), the safety profile of Alectinib remained consistent; no new safety signals were observed.
With Alectinib, 35% of patients remained on study treatment versus 9% of patients remaining on Crizotinib.
In patients with 1 or more known post-progression treatment ( Alectinib: 32.2%; Crizotinib: 45.7% ), Lorlatinib was the most common ALK TKI received after first-line Alectinib ( 7.2% ), compared with Ceritinib after first-line Crizotinib ( 15.2% ).
In conclusion, this is the first global randomized study of a 2nd generation ALK TKI to demonstrate a clinically meaningful improvement in overall survival versus Crizotinib in ALK+ NSCLC ( 5-year survival rate: 62.5%, Alectinib vs 45.5%, Crizotinib ); longer follow-up is required as OS data remained immature. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020