GeDDiS: insight into frontline therapy in soft tissue sarcoma
Mené sur 257 patients atteints d'un sarcome des tissus mous non résécable de stade localement avancé ou métastatique, cet essai de phase III compare l'efficacité, du point de vue de la proportion de patients encore vivants et de la survie sans progression à 24 semaines, et la toxicité de la doxorubicine et d'un traitement de première ligne combinant gemcitabine et docétaxel (durée médiane de suivi : 22 mois)
Gemcitabine has known activity in sarcoma; although its exact role, indication, or best combination is still debated. The combination of gemcitabine and docetaxel gained favour in the USA after efficacy was noted in uterine leiomyosarcoma1, 2 and later in sarcoma, generally with superiority over gemcitabine alone.3 However, this combination is used to a lesser extent in Europe, partly due to more equivocal data in leiomyosarcoma,4 noted efficacy of other gemcitabine-based regimens,5 and potential issues of access as described in the GeDDiS6 trial in The Lancet Oncology.6
Recently, several phase 3 studies have provided substantial insight into the use of anthracyclines and alkylators as first-line treatments for patients with advanced sarcoma.7, 8, 9 The GeDDiS6 trial iis the first to shed comparative light on the efficacy of gemcitabine and docetaxel versus doxorubicin alone in this setting. The primary endpoint of the trial—progression-free survival at 24 weeks—did not differ between the two treatment groups (46·3% [95% CI 37·5–54·6] in the doxorubicin group vs 46·4% [37·5–54·8] in the gemcitabine and docetaxel group). The GeDDiS trial investigators concluded that the combination should not be recommended as routine, while doxorubicin should remain standard of care, in the first-line setting for patients with advanced soft-tissue sarcoma.
The latter part of GeDDiS' conclusion that doxorubicin should remain routine, with a slight change in modifiers, is a logical one. Most clinicians agree that doxorubicin is a (but not necessarily the only) standard first-line therapy for patients with advanced sarcoma. However, the former part of the conclusion, that the combination should not be recommended as routine, is more debatable. The results of the GeDDiS trial should allow individual clinicians to determine how to position and in what clinical context to use gemcitabine and docetaxel for the care of their patients.
The Lancet Oncology , commentaire, 2016