1561P - Predictive diagnostics for response to therapy of chemotherapy associated anemia with darbepoetin alfa +/- intravenous iron in cancer patients: PFAD...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Supportive Care
Presenter H. Tilman Steinmetz
Authors H..T. Steinmetz1, K. Kuhr2, M. Hellmich2, M. Heinz3, M. Neise4, J. Mittermüller5, H.W. Tessen6, M. Reiser7, K. Severin1, S. Schmitz3
  • 1Outpatient clinic, 50677 - Cologne/DE
  • 2University, Institut für Medizinische Statistik, Informatik und Epidemiologie, Cologne/DE
  • 3Hematology And Oncology, Outpatient clinic, 50677 - Cologne/DE
  • 4Hematology And Oncology, Outpatient clinic, DE-47805 - Krefeld/DE
  • 5Hematology And Oncology, Outpatient clinic, Germering/DE
  • 6Hematology And Oncology, Outpatient clinic, Goslar/DE
  • 7Hematology And Oncology, PIOH - Outpatient clinic, Cologne/DE

Abstract

Introduction

Seven randomized studies have demonstrated a benefit of combining erythropoiesis stimulating agents (ESA) with intravenous iron (iv Fe) in the treatment of chemotherapy-associated anemia in cancer patients (pts). Because, so far there is no proven recommendation for the best pretherapeutic diagnostics to select optimal therapy (ESA, iron or both), we conducted a multicenter cohort study.

Methods

Cancer pts were included and eligible for response if they had a symptomatic anemia (hemoglobin (Hb) < 11g/dl), received a chemotherapy, gave written informed consent, and had a pretherapeutic diagnostics of anemia: Ferritin (F), transferrin saturation (TSAT), endogenous erythropoietin (eEPO) and soluble transferrin-receptor (sTFR) on day 1 and 14. All pts were treated with Darbepoetin alfa (DA, 500 µg, q3w) with or without iv Fe-III-hydroxyd-saccharose (200mg in 250ml NaCl 0.9% q3w). The use of iv Fe based on the recommendations of the NCCN guidelines at the discretion of the oncologists. Pts with an absolute iron deficiency (F m < 30ng/ml, f < 15ng/ml) were excluded.

Results

Between 03/07 - 08/10 in 9 outpatient clinics 331 pts received DA on day 0. Mean age was 66.3 years, 58% were women. 202 pts (61%) received at least one dose iv Fe additionally to DA on day 0. Baseline Hb was 9.53g/dl (SD 0.78) and increased in average 1.23g/dl (SD 1.34) and 1.53 g/dl (SD 1.49) til weeks 6 and 9, respectively. Transfusion rate in weeks 3-9 was 15.1%. Associations of relevant criteria with response are shown in the table. Table: 1561P

Predictive factor for response* to DA to DA with additional iv-iron to DA without iv-iron
OR (95% CI) (N)*** OR (95% CI) (N)*** OR (95% CI) (N)***
Ferritin (F) < 100 ng/ml 1.80 (0.85-3.81) (200) 4.60 (1.62-13.09) (135) 0.13 (0.02-1.07) (65)
TSAT < 20% 1.28 (0.72-2.27) (200) 1.10 (0.80-3.59) (136) 0.65 (0.24-1.76) (64)
sTFR ≥ 1.76 mg/dl 1.51 (0.87-2.60) (216) 1.70 (0.87-3.30) (146) 1.13 (0.43-2.99) (70)
FI, sTFR/logF ≤ 3.2** 3.92 (0.43-35.70) (197) 7.29 (0.38-140.76) (134) 0.57 (0.02-17.60) (63)
eEPO < 100 U/l 1.96 (0.80-4.80) (200) 2.26 (0.65-7.89) (142) 1.29 (0.34-4.90)(58)
Δ sTFR d14-1 ≥25% 1.75 (0.78-3.91) (153) 1.85 (0.73-4.68) (103) 1.98 (0.35-11.35) (50)
Δ Hb d21-1 ≥0,6 g/dl 6.09 (3.23-11.49) (189) 8.20 (3.71-18.10) (130) 3.11 (1.05-9.23) (59)
* Hb d42 ≥ 11 g/dl or Δ Hb d42-d1 ≥ 1.5 g/dl, no transfusion d21-d42 ** If CRP > 5 mg/l : FI ≤ 2 *** Odds ratio, confidence intervall, and number of pts with … … DA therapy conform with protocol, treatment response and predictive factors evaluable

Conclusion

The results confirm the increase of Hb within the first 3 weeks as strong predictor for response to DA in week 6. Pts with Hb-increase ≥ 0.6 g/dl have a 6-fold higher chance of being responders than those without. Ferritin is a stronger predictor for response to iv Fe than TSAT. Supported by Amgen, Munich, Germany.

Disclosure

H..T. Steinmetz: Member of advisory boards for Amgen, Janssen, Medice, Novartis, Roche, Vifor. Investigator in studies for Amgen, Janssen, Novartis, Roche, Vifor.,

M. Neise: Investigator in studies with Amgen,

J. Mittermüller: Investigator in studies with Amgen,

H.W. Tessen: Investigator in studies with Amgen,

M. Reiser: Investigator in studies with Amgen,

K. Severin: Ivestigator in studies with Amgen, Roche, Vifor,

S. Schmitz: Investigator in studies with Amgen, Novartis, Roche, Vifor.

All other authors have declared no conflicts of interest.