SNFGE SNFGE
 
Thématique :
- Cancer colorectal (CCR)
Originalité :
Très original
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Immédiatement
 
 
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
 
 
The Lancet Oncology
  2017/09  
 
  2017 Sep;18(9):1182-1191  
  doi: 10.1016/S1470-2045(17)30422-9.  
 
  Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.  
 
  Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T  
  https://www.ncbi.nlm.nih.gov/pubmed/28734759  
 
 

Abstract

BACKGROUND:

Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer.

METHODS:

In this ongoing, multicentre, open-label, phase 2 trial, we enrolled adults (aged ≥18 years) with histologically confirmed recurrent or metastatic colorectal cancer locally assessed as dMMR/MSI-H from 31 sites (academic centres and hospitals) in eight countries (Australia, Belgium, Canada, France, Ireland, Italy, Spain, and the USA). Eligible patients had progressed on or after, or been intolerant of, at least one previous line of treatment, including a fluoropyrimidine and oxaliplatin or irinotecan. Patients were given 3 mg/kg nivolumab every 2 weeks until disease progression, death, unacceptable toxic effects, or withdrawal from study. The primary endpoint was investigator-assessed objective response as per Response Evaluation Criteria in Solid Tumors (version 1.1). All patients who received at least one dose of study drug were included in all analyses. This trial is registered with ClinicalTrials.gov, number NCT02060188.

FINDINGS:

Of the 74 patients who were enrolled between March 12, 2014, and March 16, 2016, 40 (54%) had received three or more previous treatments. At a median follow-up of 12·0 months (IQR 8·6-18·0), 23 (31·1%, 95% CI 20·8-42·9) of 74 patients achieved an investigator-assessed objective response and 51 (69%, 57-79) patients had disease control for 12 weeks or longer. Median duration of response was not yet reached; all responders were alive, and eight had responses lasting 12 months or longer (Kaplan-Meier 12-month estimate 86%, 95% CI 62-95). The most common grade 3 or 4 drug-related adverse events were increased concentrations of lipase (six [8%]) and amylase (two [3%]). 23 (31%) patients died during the study; none of these deaths were deemed to be treatment related by the investigator.

INTERPRETATION:

Nivolumab provided durable responses and disease control in pre-treated patients with dMMR/MSI-H metastatic colorectal cancer, and could be a new treatment option for these patients.

 

 
Question posée
 
Efficacité du nivolumab dans le traitement des tumeurs colorectales métastatiques MSI prétraitées.
 
Question posée
 
Traitement efficace chez près de 70% des patients.
 
Commentaires

Première étude publiée sur un effectif important de patients atteints d’une tumeur colorectal MSI métastatique. Des résultats très encourageants avec des réponses prolongées, mais environ 30% des patients semblent réfractaires.
L’essai PRODIGE 54 – SAMCO randomisant une chimiothérapie de 2ème ligne ou une immunothérapie permettra de démontrer ou pas la supériorité de l’immunothérapie sur la chimiothérapie dans le traitement des cancers colorectaux MSI. 

 
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