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Thématique :
- Cancers autres
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Originalité :
Intermédiaire
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| Doit faire évoluer notre pratique : |
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Immédiatement
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Nom du veilleur :
Professeur David TOUGERON
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New England Journal of Medicine (NEJM)
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2017/01
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376:125-135January , 2017
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10.1056/NEJMoa1607427
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Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
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Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators.
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http://www.nejm.org/doi/full/10.1056/NEJMoa1607427
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BACKGROUND
Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)–Dotatate in patients with advanced, progressive, somatostatin-receptor–positive midgut neuroendocrine tumors.
METHODS
We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here.
RESULTS
At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame.
CONCLUSIONS
Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group.
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L’étude de phase III NETTER-1 évalue l’efficacité et l’innocuité du Lutathéra® (Lutetium-177 dotatate) chez des patients atteints de tumeurs neuroendocrines avancées, en progression et surexprimant des récepteurs de la somatostatine.
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NETTER-1 confirme l’augmentation en survie sans progression du Lutathéra® plus octréotide versus octréotide seul (survie sans progression à 20 mois de 65,2% versus 10,8%) avec une tolérance acceptable (12% d’effets secondaires hématologiques grade 3-4).
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Cette étude permet enfin de valider l’utilisation du Lutathéra® dans les tumeurs neuro-endocrines avancées et son implantation en France, évitant ainsi d’envoyer les patients à l’étranger. Des essais de stratégie sont maintenant nécessaires pour connaître le meilleur positionnement de ce traitement actuellement plutôt proposé en dernier recours en France.
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