Abstract 1156P
Background
The ALTA-1L phase III trial showed BRG significantly improved blinded independent review committee (BIRC)-assessed progression-free survival (PFS) (hazard ratio [HR]=0.48, 95% confidence interval [CI] [0.35-0.66]) and investigator (INV)-assessed PFS (HR=0.43, 95% CI [0.31-0.58]) vs CRZ in patients with ALK+ NSCLC. This study examined the treatment differences on the quality of survival of BRG vs CRZ using a quality-adjusted time without symptoms and toxicity (Q-TWiST) method based on the ALTA-1L trial.
Methods
Patient survival was partitioned into three health states: time with grade 3/4 toxicity before progression (TOX), time without disease progression or grade 3/4 toxicity (TWiST), and time with disease progression (REL). Quality-adjusted time spent in each state was calculated by applying health-state utilities to the estimated mean time in that health state. Quality-adjusted PFS (QA-PFS) and quality-adjusted overall survival (Q-TWiST) were assessed. Utilities for TOX, TWiST, and REL were assigned as 0.756, 0.793, and 0.55 (0 for QA-PFS), respectively. BIRC and INV-assessed progression (PROG) were used.
Results
Compared to patients with CRZ (n = 138), patients with BRG (n = 137) had a longer mean duration of TWiST (26.1 vs 16.9 months, P<0.001) and TOX (2.3 vs 1.1 months, P=0.064) but shorter REL (10.5 vs 19.9 months, P<0.001) using BIRC-assessed PROG. Similar results of mean duration for these three health states were found using INV-assessed PROG. There were significant improvements in QA-PFS and Q-TWiST for BRG vs CRZ using BIRC and INV-assessed PROG (Table). Table: 1156P
Mean (SE) Q-TWiST and QA-PFS by BIRC and INV-assessed PROG
| Q-TWiST (months) | ||||
| BRG | CRZ | Q-TWiST Gains | P value | |
| BIRC PROG | 28.2 (1.1) | 25.1 (1.1) | 3.1 (1.6) | 0.045 |
| INV PROG | 28.5 (1.2) | 24.8 (1.1) | 3.7 (1.6) | 0.018 |
| QA-PFS (months) | ||||
| BRG | CRZ | QA-PFS Gains | P value | |
| BIRC PROG | 22.5 (1.4) | 14.2 (1.3) | 8.3 (1.9) | <0.001 |
| INV PROG | 23.2 (1.4) | 13.1 (1.2) | 10.1 (1.8) | <0.001 |
Conclusions
In patients with advanced ALK+ NSCLC, frontline treatment with BRG was associated with significant and clinically important gains in QA-PFS and Q-TWiST compared to CRZ.
Clinical trial identification
NCT02737501.
Editorial acknowledgement
Medical writing support provided by Jane Kondejewski, PhD of SNELL Medical Communication, Inc.
Legal entity responsible for the study
Takeda Development Center Americas, Inc.
Funding
Takeda Development Center Americas, Inc.
Disclosure
M.R. Garcia Campelo: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Novartis, Eli Lilly, MSD, Janssen, Sanofi, Pfizer, Takeda, Roche; Financial Interests, Institutional, Sponsor/Funding, Research funding: BMS; Financial Interests, Institutional, Speaker’s Bureau: AstraZeneca, BMS, Novartis, Eli Lilly, MSD, Janssen, Sanofi, Pfizer, Takeda, Roche. Y. Wan, M. Lin, T. Chen, J. Shen, P. Zhang, M.J. Humphries: Financial Interests, Institutional, Full or part-time Employment: Takeda Development Center Americas, Inc. D.R. Camidge: Financial Interests, Institutional, Advisory Board: 14ner/Elevation, AbbVie, Achilles, Amgen, Anchiarno, Anheart, Apollomics, Archer, AstraZeneca, BeiGene, BeyondSpring, Bio-Thera, Blueprint, BMS, CBT Pharmaceuticals, Daiichi Sankyo, Eisai, Elevation, Eli Lilly, EMD Serono, G1 Therapeutics, GSK, Helssin, Hengrui, Janssen, Kestrel, Medtronic, Mersana, Nuvalent, Onkure, Pfizer, Puma, Qilu, Ribon, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, Turning Point; Financial Interests, Institutional, Sponsor/Funding, Research funding: Inivata; Financial Interests, Institutional, Invited Speaker, Company-sponsored trial at institution (PI role): AbbVie, AstraZeneca, Dizal, Inhibrx, Karyopharm, Pfizer, Phosplatin, Psioxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, Turning Point.