Abstract 94P
Background
Direct comparisons of lorlatinib vs alectinib for ALK+ metastatic non-small cell lung cancer (mNSCLC) are lacking, particularly for previously untreated patients with and without brain or central nervous system metastases (BM) at baseline. To address this evidence gap, matching-adjusted indirect comparisons (MAICs) based on the CROWN and ALEX trials were conducted to compare the long-term efficacy of lorlatinib vs alectinib in patients with and without baseline BM, separately.
Methods
An anchored MAIC was used to adjust for baseline differences in effect modifiers including ECOG PS, BM, and Asian race. Utilizing long-term data from CROWN and ALEX, progression-free survival (PFS) per investigator was compared within each subgroup. Observed PFS data were used where possible. Parametric survival models were required to extrapolate PFS from years 2 to 4 for crizotinib (CROWN) in the BM subgroup.
Results
After adjustment, lorlatinib demonstrated improved PFS in patients without baseline BM (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.27, 0.94). The comparison for patients with baseline BM was underpowered due to small sample sizes in CROWN and ALEX, but lorlatinib was associated with a numerically favorable benefit on PFS (HR: 0.47, 95% CI: 0.19, 1.20). The PFS probability difference at year 1 was higher in patients with (0.30, 95% CI: 0.03, 0.57) vs without (0.19, 95% CI:
Conclusions
Lorlatinib is associated with improved PFS compared to alectinib in patients with and without baseline BM, reinforcing its efficacy as a first-line treatment option for patients with ALK+ mNSCLC.
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
J. Mazieres: Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Pierre Fabre, BMS, Illumina; Financial Interests, Personal, Funding, consulting fees: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Pfizer, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen. T. Bauer: Financial Interests, Personal, Funding, consulting fees: Pfizer, Bayer, FMI; Financial Interests, Personal, Advisory Board: Pfizer, Tempus. D. Abrahami, A. Polli, H. Chu, P. Ramachandran: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. C. Chandler, M. Tan, J. Truscott: Financial Interests, Personal, Full or part-time Employment: Evidera; Financial Interests, Personal, Funding, contracted work: Pfizer. C.A. Garcia: Financial Interests, Personal, Funding, consulting fee: Pfizer; Financial Interests, Personal, Advisory Board: Regeneron.