The ALEX study has demonstrated significantly improved progression-free survival ( PFS ) with Alectinib ( Alecensa ) versus Crizotinib ( Xalkori ) in treatment-naive ALK-positive non-small-cell lung cancer ( NSCLC ) at the primary data cut-off ( 9 February 2017 ).
Researchers have reported mature progression-free survival ( cut-off: 30 November 2018 ) and overall survival ( OS ) data up to 5 years ( cut-off: 29 November 2019 ).
Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily Alectinib 600 mg ( n = 152 ) or Crizotinib 250 mg ( n = 151 ) until disease progression, toxicity, withdrawal or death.
Primary end point was investigator-assessed progression-free survival. Secondary end points included objective response rate, overall survival and safety.
Mature PFS data have shown significantly prolonged investigator-assessed PFS with Alectinib [ hazard ratio ( HR ) 0.43, 95% confidence interval ( CI ) 0.32-0.58; median PFS 34.8 versus 10.9 months Crizotinib ].
Median duration of OS follow-up was: 48.2 months Alectinib, 23.3 months Crizotinib.
OS data remain immature ( 37% of events ).
Median OS was not reached with Alectinib versus 57.4 months with Crizotinib ( stratified HR 0.67, 95% CI 0.46-0.98 ).
The 5-year OS rate was 62.5% ( 95% CI 54.3-70.8 ) with Alectinib and 45.5% ( 95% CI 33.6-57.4 ) with Crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively.
The OS benefit of Alectinib was seen in patients with central nervous system metastases at baseline [ HR 0.58 ( 95% CI 0.34-1.00 ) ] and those without [ HR 0.76 ( 95% CI 0.45-1.26 ) ].
Median treatment duration was longer with Alectinib ( 28.1 versus 10.8 months ), and no new safety signals were observed.
In conclusion, mature PFS data from ALEX have confirmed significant improvement in progression-free survival for Alectinib over Crizotinib in ALK-positive NSCLC.
OS data remain immature, with a higher 5-year OS rate with Alectinib versus Crizotinib.
This is the first global randomized study to show clinically meaningful improvement in overall survival for a next-generation tyrosine kinase inhibitor versus Crizotinib in treatment-naive ALK-positive non-small-cell lung cancer. ( Xagena )
T Mok et al, Ann Oncol 2020; 31: 1056-1064