Z Gastroenterol 2013; 51 - K61
DOI: 10.1055/s-0033-1352701

Time course of regorafenib-associated adverse events in the phase III CORRECT study

C Denzlinger 1, A Grothey 2, AF Sobrero 3, E van Cutsem 4, S Siena 5, A Falcone 6, M Ychou 7, Y Humblet 8, O Bouche 9, L Mineur 10, C Barone 11, A Adenis 12, J Tabernero 13, T Yoshino 14, HJ Lenz 15, RM Goldberg 16, F Cihon 17, A Wagner 18, D Laurent 19
  • 1Marienhospital Stuttgart, Onkologie, Hämatologie, Palliativmedizin, Stuttgart, Germany
  • 2Mayo Clinic, Rochester, United States
  • 3Arienda Ospedaliera Universitaria San Martino, Genova, Italy
  • 4Leuven Cancer Institute, Leuven, Belgium
  • 5Ospedale Niguarda Ca' Granda, Milano, Italy
  • 6Universita di Pisa, Pisa, Italy
  • 7CRLC Val d'Aurelle, Montpellier, France
  • 8Centre du Cancer de l'Universite Catholique de Louvain, Brussels, Belgium
  • 9University Hospital Robert Debre, Reims, France
  • 10Institut Sainte-Catherine, Avignon, France
  • 11Catholic University, Roma, Italy
  • 12Centre Oscar Lambret, Lille, France
  • 13Vall d'Hebron Institute of Oncology, Barcelona, Spain
  • 14National Cancer Center Hospital East, Chiba, Japan
  • 15USC Norris Comprehensive Cancer Center, Los Angeles, United States
  • 16Ohio State University, Columbus, United States
  • 17Bayer Healthcare Pharmaceuticals, Montville, United States
  • 18Bayer Pharma AG, Berlin, Germany
  • 19Bayer Healthcare Pharmaceuticals, Berlin, Germany

Aims: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs. placebo in the randomized Phase III CORRECT study.

Methods: We examined the time course of adverse events (AEs) in the CORRECT study.

Results: The safety population comprised 753 patients (pts): REG n = 500; placebo n = 253. The mean treatment duration was 12.1 ± 9.7 weeks in the REG group and 7.8 ± 5.2 weeks in the placebo group. Treatment-emergent AEs occurred at any grade in 99.6% of REG pts and 96.8% of placebo pts, at grade 1/2 in 21.6% and 47.8%, respectively, at grade 3 in 56.0% and 26.5%, respectively, and at grade 4/5 in 22.0% and 22.5%, respectively. AEs occurring in ≥10% more REG than placebo pts were fatigue, hand-foot skin reaction (HFSR), anorexia, diarrhea, weight loss, voice changes, hypertension, rash/desquamation, oral mucositis, fever, hyperbilirubinemia, low platelet count. The most frequent AEs deemed to be regorafenib related were HFSR, fatigue, diarrhea, hypertension, and rash/desquamation. The frequency of these AEs over time is shown in the Table. The incidence of HFSR, fatigue, hypertension, and rash/desquamation peaked in cycle 1 and tapered to a relatively stable lower incidence over later cycles. The incidence of diarrhea remained relatively constant throughout treatment. AEs led to dose modification in 66.6% of pts in the REG group and 22.5% in the placebo group. Data on dose intensity across treatment cycles will be presented.

Conclusions: In the CORRECT trial, the incidences of the most common AEs in the REG group peaked early during treatment. There appeared to be no evidence for cumulative toxicity of REG.

Clinical trial information: NCT01103323.

Table 1: Frequency (%) of treatment-emergent AEs over time

Cycle 1

Cycle 2

Cycle 3

Cycle 4

Cycle 5

Cycle 6

Cycle 7

Cycle 8

Cumulative

n

500

417

229

193

119

91

55

43

500

HFSR

32

26

24

24

26

25

15

5

47

Fatigue

45

23

16

24

17

22

11

9

63

Diarrhea

23

20

21

26

21

18

13

14

43

Hypertension

21

11

3

4

4

2

0

5

30

Rash/desquamation

24

7

3

4

5

1

0

0

29