858P - Addition of darbepoetin alfa to sequential high dose vip chemotherapy for patients with advanced metastatic germ cell cancer

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Germ Cell Tumours
Presenter Jorg Hartmann
Authors J.T. Hartmann1, B. Metzner2, C. Binder3, H. Mergenthaler4, O. Rick5, H.G. Sayer6, A. Lorch7, W.E. Berdel8, C. Bokemeyer9, T.C. Gauler10
  • 1Medical Oncology, Christian-Albrechts-Universität zu Kiel, 24105 - Kiel/DE
  • 2Abt. Onkologie/haematologie, Klinikum Oldenburg, DE-26133 - Oldenburg/DE
  • 3Hämatologie Und Onkologie, Universitätsmedizin Göttingen, Göttingen/DE
  • 4Klinik F. Onkologie, Klinikum Stuttgart - KatharinenhospitalKlinik f. Onkologie, DE-70174 - Stuttgart/DE
  • 5Oncology, Klinik Reinhardshoehe, DE-34537 - Bad Wildungen/DE
  • 6Klinik Für Innere Medizin Ii, Universitätsklinikum Jena, Jena/DE
  • 7Urologische Klinik, Universitätsklinikum Düsseldorf, Düsseldorf/DE
  • 8Medizinische Klinik A, Universitaetsklinikum Münster, DE-48149 - Münster/DE
  • 9Dept. Hemato/oncology, UKE II. Medizinische Klinik und PoliklinikMedizinische Klinik II., 20246 - Hamburg-Eppendorf/DE
  • 10Dept. Of Medicine (cancer Research), University Hospital, 45122 - Essen/DE

Abstract

Background

High-dose VIP chemotherapy (HD-VIP) plus ABSCT given as first line treatment might be a strategy in patients with advanced germ cell tumors (GCT) with poor prognosis. The objective of the trial was to investigate the addition of darbepoetin alfa to HD-VIP in order to reduce anemia/red blood cell (RBC) transfusions.

Methods

This was a randomized, open-label multicenter phase 2 study conducted in 20 hospitals. Darbepoetin 2,25 mcg/kg weekly or 500 mcg Q3W s.c., started with HD-VIP (dose level 6), was applied in arm B (arm A: HD-VIP alone). The primary objective was freedom from blood transfusions (FFT). Secondary objectives included objective remission rate (ORR) after chemotherapy, 24-mos PFS and OS, median course of hemoglobin (Hb) levels during 3 HD-VIP cycles as well as drug safety.

Results

Between 7/2003 and 11/2008 108 pts were allocated to the study, and 102 were included in the intention-to-treat (ITT) analysis. By March 2012, the median follow-up time after randomization was 62 (range, 3–100) mos for surviving patients. Localisation of primary was gonadal in 66%, retroperitoneal in 19% and mediastinal in 14%s. A favourable treatment outcome (CR/NED/PR m-) in conjunction with secondary surgery (n = 76 pts) was achieved in 58% of pts with no difference between arms A and B. Overall FFT occurred in 2 pts (4.2%) in arm A and 3 pts (5.6%) in arm B, and in 23%/15%/15% and 15%/17%/19% of pts during cycles 1-3, respectively. No differences in baseline Hb, severity of anemia, number of RBC transfusions and area under the curve of Hb levels during HD-VIP was observed. Pts assigned to darbepoetin had similar treatment toxicity compared to those assigned to HD-VIP alone. 5-year OS in arm A was 74.0% compared to 63.0% (P = .18) in Arm B. 5-year DFS was 60.5% in arm A vs 53.1% in Arm B (P = 0.54). Darbepoetin was generally well tolerated with 2 pts discontinuing treatment due to thrombosis. A per-protocol (PP) analysis revealed comparable outcomes (OS 74.4 vs 67.5, P = 0.38; DFS 60.4 vs 58.3, P = 0.70).

Conclusions

Based on ITT and PP analysis, the addition of darbepoetin alfa to HD-VIP compared to HD-VIP alone does not appear to impact FFT, ORR, and survival in poor prognosis GCT pts (NCT00204633).

Disclosure

All authors have declared no conflicts of interest.