PMID- 37644967
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231121
IS  - 2666-3643 (Electronic)
IS  - 2666-3643 (Linking)
VI  - 4
IP  - 8
DP  - 2023 Aug
TI  - Lorlatinib Tolerability and Association With Clinical Outcomes in Patients With 
      Advanced ALK- or ROS1-Rearranged NSCLC: A Brief Report.
PG  - 100546
LID - 10.1016/j.jtocrr.2023.100546 [doi]
LID - 100546
AB  - INTRODUCTION: Treatment with lorlatinib for patients with advanced ALK- and 
      ROS1-rearranged NSCLC (ALK+ and ROS1+ NSCLC) is associated with a unique set of 
      adverse events (AEs) often requiring dose reduction. However, the impact of dose 
      reductions on outcomes remains unclear and is mainly limited to analyses from 
      prospective studies of lorlatinib in the first-line setting. METHODS: We reviewed 
      the course of 144 patients with advanced ALK- or ROS1-rearranged NSCLC treated 
      with lorlatinib in the second-line or later setting to assess the frequency of 
      dose reductions resulting from treatment-related AEs (TRAEs) and the association 
      between dose reductions and progression-free survival (PFS) and overall survival 
      (OS). RESULTS: A total of 58 patients (40%) had TRAE-related dose reductions, 
      most (59%) owing to neurocognitive AEs or neuropathy. Among all patients, the 
      median PFS was 8.1 months (95% confidence interval [CI]: 6.4-11.8); the median OS 
      was 20.7 months (95% CI: 16.3-30.5). Among patients who were started on 
      lorlatinib 100 mg/d (n = 122), a Cox regression model with the occurrence of a 
      dose reduction as a time-dependent covariate indicated no association between 
      dose reduction and PFS (hazard ratio = 0.86, 95% CI: 0.54-1.39) or OS (hazard 
      ratio = 0.78, 95% CI: 0.47-1.30). CONCLUSIONS: Lorlatinib dose reductions were 
      not associated with inferior clinical outcomes in this multicenter analysis. 
      Prompt identification of lorlatinib TRAEs and implementation of dose reductions 
      may help maximize tolerability without compromising outcomes.
CI  - (c) 2023 The Authors.
FAU - Thummalapalli, Rohit
AU  - Thummalapalli R
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Choudhury, Noura J
AU  - Choudhury NJ
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Ehrich, Fiona
AU  - Ehrich F
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Beardslee, Tyler
AU  - Beardslee T
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University School of Medicine, Atlanta, Georgia.
FAU - Brazel, Danielle
AU  - Brazel D
AD  - Chao Family Comprehensive Cancer Center, University of California Irvine School 
      of Medicine, Orange, California.
FAU - Zhang, Shannon S
AU  - Zhang SS
AD  - Chao Family Comprehensive Cancer Center, University of California Irvine School 
      of Medicine, Orange, California.
FAU - Merchant, Shelby
AU  - Merchant S
AD  - Department of Pharmacy, Levine Cancer Institute, Atrium Health, Charlotte, North 
      Carolina.
FAU - Chen, Monica F
AU  - Chen MF
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Heller, Glenn
AU  - Heller G
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Ramalingam, Suresh S
AU  - Ramalingam SS
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University School of Medicine, Atlanta, Georgia.
FAU - Ou, Sai-Hong Ignatius
AU  - Ou SI
AD  - Chao Family Comprehensive Cancer Center, University of California Irvine School 
      of Medicine, Orange, California.
FAU - Mileham, Kathryn F
AU  - Mileham KF
AD  - Thoracic Medical Oncology, Levine Cancer Institute, Atrium Health, Charlotte, 
      North Carolina.
FAU - Riely, Gregory J
AU  - Riely GJ
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20230630
PL  - United States
TA  - JTO Clin Res Rep
JT  - JTO clinical and research reports
JID - 101769967
PMC - PMC10460990
OTO - NOTNLM
OT  - ALK
OT  - Lorlatinib
OT  - Non-small cell lung cancer
OT  - ROS1
OT  - Toxicity
EDAT- 2023/08/30 06:48
MHDA- 2023/08/30 06:49
PMCR- 2023/06/30
CRDT- 2023/08/30 03:44
PHST- 2023/04/20 00:00 [received]
PHST- 2023/06/12 00:00 [revised]
PHST- 2023/06/24 00:00 [accepted]
PHST- 2023/08/30 06:49 [medline]
PHST- 2023/08/30 06:48 [pubmed]
PHST- 2023/08/30 03:44 [entrez]
PHST- 2023/06/30 00:00 [pmc-release]
AID - S2666-3643(23)00089-9 [pii]
AID - 100546 [pii]
AID - 10.1016/j.jtocrr.2023.100546 [doi]
PST - epublish
SO  - JTO Clin Res Rep. 2023 Jun 30;4(8):100546. doi: 10.1016/j.jtocrr.2023.100546. 
      eCollection 2023 Aug.