PMID- 36092332
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220913
IS  - 2078-6891 (Print)
IS  - 2219-679X (Electronic)
IS  - 2078-6891 (Linking)
VI  - 13
IP  - 4
DP  - 2022 Aug
TI  - A post-marketing safety study of ramucirumab with FOLFIRI in patients with 
      metastatic colorectal cancer.
PG  - 1701-1710
LID - 10.21037/jgo-21-863 [doi]
AB  - BACKGROUND: Ramucirumab [human vascular endothelial growth factor (VEGF) 
      receptor-2 monoclonal antibody] + levofolinate, fluorouracil, and irinotecan 
      (FOLFIRI) was approved for the treatment of metastatic colorectal cancer (CRC) in 
      Japan based on the results from the phase 3 RAISE trial (NCT01183780). However, 
      safety information of ramucirumab + FOLFIRI in the real-world setting is limited. 
      Therefore, the present study was conducted to evaluate the safety of ramucirumab 
      + FOLFIRI under routine clinical practice in patients with metastatic CRC (mCRC) 
      after first-line chemotherapy. METHODS: A single-arm, prospective, multicenter, 
      non-interventional, observational study was conducted between August 2016 and May 
      2020. Patients with mCRC treated with ramucirumab + FOLFIRI for the first time 
      were included. Patients were observed for 12 months from the start of 
      ramucirumab. Data were recorded using the electronic data capture system. 
      RESULTS: In total, 362 patients with a mean age of 64.1 years were evaluated for 
      safety, of whom 355 patients were evaluated for effectiveness. A higher 
      proportion of the patients were males (n=200; 55.2%), had metastases and 
      recurrent sites (n=362, 100.0%), and had received prior anti-cancer treatment 
      (n=355; 98.1%). Approximately 83.7% (n=303) and 25.4% (n=92) of patients had 
      medication history of bevacizumab and anti-epidermal growth factor receptor 
      (EGFR) antibodies, respectively. Overall, 84.3% (n=305) of patients experienced 
      any grade adverse events (AEs). Neutrophil count decreased (n=138; 38.1%), 
      hypertension (n=58; 16.0%), and diarrhea (n=57; 15.7%) were observed frequently. 
      The clinically relevant grade >/=3 AEs of special interest (AESIs) with >2% 
      incidence included neutropenia (n=101; 27.9%), hypertension (n=35; 9.7%), 
      proteinuria (n=23; 6.4%), hepatic dysfunction (n=15; 4.1%), febrile neutropenia 
      (n=10; 2.8%), and leukopenia (n=9; 2.5%). The presence of renal disease at 
      baseline increased the risk of proteinuria [risk ratio: 2.1; 95% confidence 
      interval (CI): 1.1-4.2]. Three deaths were reported due to AEs, of which 1 was 
      study treatment related. The 12-month survival rate of the ramucirumab + FOLFIRI 
      regimen was 59%, mortality mainly (90%) occurring due to progressive disease. 
      CONCLUSIONS: Although the current observational study enrolled patients with 
      various medication history, the regimen of ramucirumab + FOLFIRI was manageable 
      under clinical practice. No new safety concerns beyond the findings observed in 
      previous clinical trials were reported.
CI  - 2022 Journal of Gastrointestinal Oncology. All rights reserved.
FAU - Masuishi, Toshiki
AU  - Masuishi T
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
FAU - Nagaoka, Soshi
AU  - Nagaoka S
AD  - Eli Lilly Japan K.K., Kobe, Japan.
FAU - Jin, Long
AU  - Jin L
AD  - Eli Lilly Japan K.K., Kobe, Japan.
FAU - Yoshizawa, Kenichi
AU  - Yoshizawa K
AD  - Eli Lilly Japan K.K., Kobe, Japan.
LA  - eng
PT  - Journal Article
PL  - China
TA  - J Gastrointest Oncol
JT  - Journal of gastrointestinal oncology
JID - 101557751
PMC - PMC9459187
OTO - NOTNLM
OT  - Colorectal cancer (CRC)
OT  - metastatic
OT  - neutropenia
OT  - proteinuria
OT  - ramucirumab
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://jgo.amegroups.com/article/view/10.21037/jgo-21-863/coif). TM has received 
      personal fees from Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Lilly Japan, 
      Yakult Honsha, Ono, Bristol Myers Squibb, Daiichi Sankyo, and Sanofi, and grants 
      from MSD, Daiichi Sankyo, Ono, and Novartis. SN is an employee of Eli Lilly Japan 
      K.K. and the present manuscript was supported by the company. SN is a shareholder 
      of Eli Lilly and Company. LJ is an employee of Eli Lilly Japan K.K. and the 
      present manuscript and medical writing were supported by the company. KY is an 
      employee of Eli Lilly Japan K.K. and the present manuscript was supported by the 
      company. KY is a shareholder of Eli Lilly and Company, Bristol-Myers Squibb 
      Company and Merck & Co., Inc. The authors have no other conflicts of interest to 
      declare.
EDAT- 2022/09/13 06:00
MHDA- 2022/09/13 06:01
PMCR- 2022/08/01
CRDT- 2022/09/12 04:14
PHST- 2021/12/09 00:00 [received]
PHST- 2022/04/24 00:00 [accepted]
PHST- 2022/09/12 04:14 [entrez]
PHST- 2022/09/13 06:00 [pubmed]
PHST- 2022/09/13 06:01 [medline]
PHST- 2022/08/01 00:00 [pmc-release]
AID - jgo-13-04-1701 [pii]
AID - 10.21037/jgo-21-863 [doi]
PST - ppublish
SO  - J Gastrointest Oncol. 2022 Aug;13(4):1701-1710. doi: 10.21037/jgo-21-863.