Characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) who had progression-free survival (PFS) >4 months (m): Subgroup analysis of the phase 3 CORRECT trial

Date

08 Oct 2016

Session

Poster Display

Presenters

Axel Grothey

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

A. Grothey1, A. Falcone2, Y. Humblet3, O. Bouche4, L. Mineur5, A. Adenis6, J. Tabernero7, T. Yoshino8, H. Lenz9, R.M. Goldberg10, L. Huang11, A. Wagner12, E. Van Cutsem13

Author affiliations

  • 1 Department Of Oncology, Mayo Clinic, 55905 - Rochester/US
  • 2 Department Of Oncology, University of Pisa, Pisa/IT
  • 3 Medical Oncology Department, St-Luc University Hospital, Brussels/BE
  • 4 Digestive Oncology, Centre Hospitalier Universitaire Robert Debré, Reims/FR
  • 5 Gi And Liver Cancer Unit Oncology And Radiotherapy, Institut Ste Catherine, Avignon/FR
  • 6 Department Of Gastrointestinal Oncology, Centre Oscar Lambret, Lille/FR
  • 7 Department Of Medical Oncology, Vall d’Hebron University Hospital and Institute of Oncology, Barcelona/ES
  • 8 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 9 Division Of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles/US
  • 10 Department Of Medicine, The Ohio State University Comprehensive Cancer Center and James Cancer Hospital, Columbus/US
  • 11 Clinical Statistics Us, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 12 Global Clinical Development, Bayer Pharma AG, Berlin/DE
  • 13 Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven/BE
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Background

In CORRECT, REG significantly improved overall survival and PFS vs placebo in pts with treatment-refractory mCRC. We did a retrospective, exploratory subgroup analysis of REG-treated pts in CORRECT with PFS >4 m (long PFS) and ≤4 m (short PFS).

Methods

Pts with pretreated mCRC were randomized 2:1 to REG 160 mg or placebo QD for 3 weeks on/1 week off until disease progression, death, or unacceptable toxicity. PFS was the time from randomization to progression or death. Of 505 pts randomized to REG, 98 (19%) had long PFS and 407 (81%) had short PFS.

Results

Compared to short PFS pts, the long PFS group had a higher proportion of patients with ECOG PS0, 1–2 tumor sites, and ≥18 m since diagnosis of metastatic disease (Table). Long PFS pts received a median of 6 (1–12) cycles, short PFS pts a median of 2 (1–11). Mean actual daily doses were 138.7 mg (long PFS) and 149.2 mg (short PFS). Dose modifications occurred in 91% (long PFS) and 72% (short PFS). NCI-CTCAE (v3) grade (Gr) ≥3 REG-related treatment-emergent adverse events (TEAE) occurred in 64% (long PFS) and 53% (short PFS). Most common REG-related Gr ≥3 TEAEs included (long PFS, short PFS) hand–foot skin reaction (20%, 16%), hypertension (17%, 5%), fatigue (13%, 9%), diarrhea (16%, 5%), rash/desquamation (3%, 6%), and hypophosphatemia (5%, 3%). Gr ≥3 laboratory toxicities (long PFS, short PFS) included increased bilirubin (8%, 13%), ALT (6%, 5%), and AST (5%, 6%). Although REG-related TEAEs led to a higher dose modification rate in long PFS pts (71% vs 52% for short PFS), discontinuations due to REG-related TEAEs were similar (long PFS 5%; short PFS 9%).

Long PFS (n = 98) Short PFS (n = 407)
Median age, yrs (range) 61 (34–82) 61 (22–82)
Male, % 64 61
Median body mass index, kg/m2 25.6 24.7
ECOG PS, % 0 1 63 37 50 50
No. of tumor sites, % 1 2 3 ≥4 30 38 16 16 17 35 30 18
KRAS status, % mutant wildtype 47 44 56 40
Primary site of disease, % Colon Rectum Both 52 37 10 67 28 5
No. of prior regimens on or after diagnosis of metastatic disease, % 0–2 3 ≥4 22 22 55 28 25 47
Time since first diagnosis of metastatic disease to randomization, %

Conclusions

This exploratory analysis showed that pts with mCRC treated with REG who had PFS >4 m tended to have a better performance status, fewer metastatic tumor sites, and a longer time since diagnosis of metastatic disease, compared to pts with short PFS.

Clinical trial identification

NCT01103323

Legal entity responsible for the study

Bayer

Funding

Bayer

Disclosure

A. Grothey: Advisory board: Bayer. Corporate-sponsored research: Bayer. A. Falcone: Advisory board: Amgen, Roche, Bayer, Lilly, Sanofi, Servier, Merck. Corporate-sponsored research: Roche, Amgen, Bayer, Merck, Sanofi. O. Bouche: Advisory board: Merck Serono, Roche. L. Mineur: Advisory board participation. A. Adenis: Corporate-sponsored research: Bayer, Sanofi Other substantive relationship: Bayer, Sanofi, Pfizer, Roche. J. Tabernero: Advisory board: Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Symphogen, Takeda, Taiho. T. Yoshino: Corporate-sponsored research: GlaxoSmithKline K.K. Boehringer Ingelheim GmbH H-J. Lenz: Advisory board: Bayer. Lectures: Bayer. Clinical trial support: Bayer. R.M. Goldberg: Corporate-sponsored research: Bayer. L. Huang: Stock ownership: Bayer Other substantive relationships: Bayer (employee). A. Wagner: Other substantive relationships: Bayer (employee). E. Van Cutsem: Corporate-sponsored research: Bayer. All other authors have declared no conflicts of interest.

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