SNFGE SNFGE
 
Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
 
 
The Lancet Oncology
  2019/03  
 
  2019 Mar;20(3):420-435.  
  doi: 10.1016/S1470-2045(18)30791-5.  
 
  Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial.  
 
  Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group.  
  https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30791-5/fulltext  
 
 

Abstract

BACKGROUND:

VEGF and VEGF receptor 2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether the addition of ramucirumab, a VEGFR-2 antagonist monoclonal antibody, to first-line chemotherapy improves outcomes in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma.

METHODS:

For this double-blindrandomisedplacebo-controlledphase 3 trial done at 126 centres in 20 countries, we recruited patientsaged 18 years or older with metastatic, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Eligible patients were randomly assigned (1:1) with an interactive web response system to receive cisplatin (80 mg/m2, on the first day) plus capecitabine (1000 mg/m2, twice daily for 14 days), every 21 days, and either ramucirumab (8 mg/kg) or placebo on days 1 and 8, every 21 days. 5-Fluorouracil (800 mg/m2 intravenous infusion on days 1-5) was permitted in patients unable to take capecitabine. The primary endpoint was investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients. We did a sensitivity analysis of the primary endpoint, including a central review of CT scans. Overall survival was a key secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02314117.

FINDINGS:

Between Jan 28, 2015, and Sept 16, 2016, 645 patients were randomly assigned to receive ramucirumab plus fluoropyrimidineand cisplatin (n=326) or placebo plus fluoropyrimidine and cisplatin (n=319). Investigator-assessed progression-free survival was significantly longer in the ramucirumab group than the placebo group (hazard ratio [HR] 0·753, 95% CI 0·607-0·935, p=0·0106; median progression-free survival 5·7 months [5·5-6·5] vs 5·4 months [4·5-5·7]). A sensitivity analysis based on central independent review of the radiological images did not corroborate the investigator-assessed difference in progression-free survival (HR 0·961, 95% CI 0·768-1·203, p=0·74). There was no difference in overall survival between groups (0·962, 0·801-1·156, p=0·6757; median overall survival 11·2 months [9·9-11·9] in the ramucirumab group vs 10·7 months [9·5-11·9] in the placebo group). The most common grade 3-4 adverse events were neutropenia (85 [26%] of 323 patients in the ramucirumab group vs 85 [27%] of 315 in the placebo group), anaemia (39 [12%] vs 44 [14%]), and hypertension (32 [10%] vs 5 [2%]). The incidence of any-grade serious adverse events was 160 (50%) of 323 patients in the ramucirumab group and 149 (47%) of 315 patients in the placebo group. The most common serious adverse events were vomiting (14 [4%] in the ramucirumab group vs 21 [7%] in the placebo group) and diarrhoea (11 [3%] vs 19 [6%]). There were seven deaths in each group, either during study treatment or within 30 days of discontinuing study treatment, which were the result of treatment-related adverse events. In the ramucirumab group, these adverse events were acute kidney injury, cardiac arrest, gastric haemorrhage, peritonitis, pneumothorax, septic shock, and sudden death (n=1 of each). In the placebo group, these adverse events were cerebrovascular accident (n=1), multiple organ dysfunction syndrome (n=2), pulmonary embolism (n=2), sepsis (n=1), and small intestine perforation (n=1).

INTERPRETATION:

Although the primary analysis for progression-free survival was statistically significant, this outcome was not confirmed in a sensitivity analysis of progression-free survival by central independent review, and did not improve overall survival. Therefore, the addition of ramucirumab to cisplatin plus fluoropyrimidine chemotherapy is not recommended as first-line treatment for this patient population.

 

 
Question posée
 
L’association du ramucirumab à la chimiothérapie améliore-t-elle la survie sans progression comparé à la chimiothérapie seule chez les patients atteints d’adénocarcinome de l’estomac métastatique traités en 1ère ligne ?
 
Question posée
 
Non.
 
Commentaires

Comme le bévacizumab, le ramucirumab échoue à démontrer une efficacité statistiquement significative en 1ère ligne de traitement des adénocarcinomes gastriques métastatiques, bien que le ramucirumab soit efficace en 2ème ligne. Il est urgent de trouver des biomarqueurs d’efficacité des antiangiogéniques dans le traitement des adénocarcinomes gastriques.

 
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