Evaluating the Optimal TKI for Patients With ALK Positive Advanced Non-Small-Cell Lung Cancer (aNSCLC) in the First Line (1L) Setting: An Updated Systematic Literature Review (SLR) and Network Meta-Analysis (NMA)
Author(s)
Ou SH1, Le H2, Aiello E3, Bradbury J4, Ghoshal D5, Taneja A5, Kilvert H4, Polli A6, Rifi N6, Zala D6, Luan L7, Zhu F8, Han B9
1UCI School of Medicine, University of California, Irvine, California, Irvine, CA, USA, 2Pfizer, Inc., Fairfax, VA, USA, 3Lumanity, Toronto, ON, Canada, 4Lumanity, SHEFFIELD, DBY, UK, 5Lumanity, Gurugram, HR, India, 6Pfizer, Inc., New York, NY, USA, 7Pfizer Investment Co., Ltd., Beijing, 11, China, 8Pfizer Investment Co., Ltd., Shanghai, Changning, China, 9Shanghai Chest Hospital, Shanghai, Changning, China
Presentation Documents
OBJECTIVES: To understand the relative effects of 1L lorlatinib compared with other tyrosine kinase inhibitors (TKIs) in patients with ALK+ aNSCLC. We report an updated analysis of a previous SLR and NMA.
METHODS: This NMA used recent results from 5-year CROWN data and 11 comparator studies. Besides alectinib and brigatinib, this analysis also included ensartinib, envonalkib and iruplinalkib. The primary analysis investigated progression-free survival (PFS) by investigator-assessed (INV). Secondary outcomes included PFS by blinded independent central review (BICR), intracranial (IC) time-to-progression (TTP), grade ≥3/4 adverse events (AEs), discontinuation rates due to treatment-related adverse events (AEDC), and overall survival (OS). PFS BICR and OS were not updated with CROWN 5Y data. PFS INV and IC-TTP was also analyzed in subgroups of patients with and without baseline brain metastases (w&w/o BM). Review of 10 other independent NMAs were completed.
RESULTS: Preliminary results showed Lorlatinib presented significantly better PFS INV versus alectinib 600mg/brigatinib/ensartinib/envonalkib/iruplinalkib (HR 95% credible interval (CrI): 0.49(0.32-0.75)/0.44 (0.27-0.72)/0.42(0.25-0.7)/0.45(0.28-0.74)/0.48(0.29-0.78), respectively. These results were consistent with PFS BICR, IC-TPP, and within subgroups of patients w&w/o BM.
Updated NMA data for AEs is similar to previous data showing higher odds of grade ≥3 AEs than alectinib, and numerically higher odds than other TKIs. However, the AEDC remained either similar vs alectinib and numerically lower vs. other TKIs, indicating that AEs are manageable. One additional NMA was identified in this update, and results still showed consistent findings that lorlatinib demonstrated a numerically or significantly better PFS vs. alectinib and brigatinib. Other NMAs only included 3Y data, and no other NMAs looked at data vs. iruplinalkib.CONCLUSIONS: With the unprecedented CROWN 5Y data (Solomon et al., JCO 2024), the relative effect of 1L lorlatinib is significantly improved vs. other TKIs. Totality of evidence across available NMAs consistently support lorlatinib as preferred 1L treatment of choice for ALK+ aNSCLC patients.
Conference/Value in Health Info
Value in Health, Volume 27, Issue 12, S2 (December 2024)
Code
SA59
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis, Meta-Analysis & Indirect Comparisons
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology