PMID- 31656659
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220411
IS  - 2072-1439 (Print)
IS  - 2077-6624 (Electronic)
IS  - 2072-1439 (Linking)
VI  - 11
IP  - 9
DP  - 2019 Sep
TI  - Real world experience on treatment, outcome and toxicity of crizotinib in 
      patients with anaplastic lymphoma kinase positive advanced non-small cell lung 
      cancer.
PG  - 3864-3873
LID - 10.21037/jtd.2019.09.15 [doi]
AB  - BACKGROUND: Crizotinib has been the standard treatment for patients with 
      anaplastic lymphoma kinase (ALK)-rearranged advanced non-small cell lung cancer 
      (NSCLC). It demonstrated superior progression-free survival (PFS) and higher 
      objective response rates (ORRs) vs. chemotherapy in previously treated and 
      untreated patients with ALK-positive advanced NSCLC. This retrospective analysis 
      reports real-world experience in treatment outcome and toxicity of crizotinib in 
      this group of patients, with a focus on the cardiac toxicity and its management. 
      METHODS: Twenty-two patients diagnosed with ALK-positive NSCLC, either by 
      immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), treated 
      at Johns Hopkins Singapore International Medical Centre (JHSIMC) and Tan Tock 
      Seng Hospital (TTSH) in Singapore, were identified and followed for a median of 
      18 months. Data were collected and analyzed for baseline demographics, PFS, ORR, 
      duration of response, toxicity and overall survival (OS). RESULTS: Clinical 
      profile of patients included in the study was similar with clinical trials on 
      crizotinib. Most patients were young of mean age 42, non-smokers and with good 
      performance status. Fifty-nine percent had prior chemotherapy. Fifty percent of 
      patients had brain metastases (BM), either de novo or on progression. ORR of 
      crizotinib was 64% with median total duration of treatment of 8.5 months (range, 
      2-73(+) months). Median PFS for patients treated with first-line crizotinib was 
      15 months. Most patients with BM had brain radiation. Median time for 
      intracranial progression from the start of crizotinib was 11 months. Those with 
      stable or responding extracranial disease continued crizotinib after radiotherapy 
      to the brain. Median duration of response in this group of patients was 14 months 
      (range, 2-31 months). Median OS among patients treated with upfront crizotinib 
      was not reached, with 7 out of 11 patients still alive at the time of data 
      analysis (n=11, range, 1-73(+)). Toxicity was manageable with moderate rate of 
      grade 3 or worse toxicity (n=7, 31.8%). Three patients had grade 3-4 neutropenia. 
      Eighteen percent (n=4) of patients developed cardiotoxicities such as 
      bradycardia, prolonged QTc interval and complete heart block. One patient who 
      developed complete heart block required pacemaker insertion. Two patients are 
      long term responders who have been on crizotinib for 68(+) and 73(+) months. 
      CONCLUSIONS: This retrospective analysis of a real-world experience confirms the 
      therapeutic benefit of crizotinib in advanced ALK-positive NSCLC. Our data showed 
      crizotinib is tolerable and effective, comparable with literature report. 
      Occasional serious cardiac toxicity requires attention.
CI  - 2019 Journal of Thoracic Disease. All rights reserved.
FAU - Del Valle, Maria Fatima Flores
AU  - Del Valle MFF
AD  - Department of Medical Oncology, Tan Tock Seng Hospital, Johns Hopkins Singapore 
      Pte Ltd., Singapore.
FAU - Chang, Alex Yuang-Chi
AU  - Chang AY
AD  - Department of Medical Oncology, Tan Tock Seng Hospital, Johns Hopkins Singapore 
      Pte Ltd., Singapore.
LA  - eng
PT  - Journal Article
PL  - China
TA  - J Thorac Dis
JT  - Journal of thoracic disease
JID - 101533916
PMC - PMC6790458
OTO - NOTNLM
OT  - Anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer 
      (NSCLC)
OT  - brain metastases (BM)
OT  - cardiotoxicity
OT  - crizotinib
OT  - treatment outcomes
COIS- Conflicts of Interest: Dr. Chang has served as a member of the local advisory 
      board of Bristol Myers Squibb (BMS), Mercke Sharpe and Dohme (MSD), Pfizer, 
      Novartis and Celgene. He has received clinical research grant support from BMS, 
      MSD, Pfizer, Astra Zeneca, Exelixis and Merck KGaA. Dr. Del Valle has no 
      conflicts of interest to declare.
EDAT- 2019/10/28 06:00
MHDA- 2019/10/28 06:01
PMCR- 2019/09/01
CRDT- 2019/10/29 06:00
PHST- 2019/10/29 06:00 [entrez]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2019/10/28 06:01 [medline]
PHST- 2019/09/01 00:00 [pmc-release]
AID - jtd-11-09-3864 [pii]
AID - 10.21037/jtd.2019.09.15 [doi]
PST - ppublish
SO  - J Thorac Dis. 2019 Sep;11(9):3864-3873. doi: 10.21037/jtd.2019.09.15.