LBA22 - FOLFOX / Bevacizumab (Beva) +/- Irinotecan in advanced colorectal cancer (CRC): A randomized phase II trial (AIO KRK 0209, CHARTA)

Date 10 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, colorectal
Topics Colon and Rectal Cancer
Presenter Hans Joachim Schmoll
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors H.J. Schmoll1, B. Garlipp2, C. Junghanß3, M. Leithauser4, A. Vogel5, M. Schaefers6, U. Kaiser7, H.G. Hoeffkes8, A. Florschütz9, J. Ruessel10, S. Kanzler11, T. Edelmann12, H. Forstbauer13, T. Göhler14, C. Hannig15, B. Hildebrandt16, J. Steighardt17, F.M. Meinert18, F. Cygon18, A. Stein19
  • 1Dept. Hematology/ Oncology Fg 16 / U1, Martin Luther University of Halle, 06120 - Halle/DE
  • 2Klinik Für Chirurgie, Otto-von Guericke-Universität, 39120 Magdeburg - Magdeburg/DE
  • 3Klinik Für Innere Medizin Iii, Universitätsklinikum Rostock, 18057 Rostock - Rostock/DE
  • 4Praxis, c/o Praxis Drs. Lakner/Decker, 18057 - Rostock/DE
  • 5Gastroenterology, Hepatology And Endokrinology, Hannover Medical School, 30625 - Hannover/DE
  • 6Onkologische Schwerpunktpraxis, Praxis, 40489 Düsseldorf - Düsseldorf/DE
  • 7Onkologisches Zentrum, St. Bernward Hopsital, 31134 - Hildesheim/DE
  • 8Mvz Osthessen, Klinikum Fulda gAG, Fulda - Fulda/DE
  • 9Klinik Für Innere Medizin, Städtisches Klinikum Dessau, 06847 Dessau - Dessau/DE
  • 10Oncology And Hematology, University of Halle, 06120 - Halle/Saale/DE
  • 11Clinic For Internal Medicine 2, Leopoldina Krankenhaus Medizinische Klinik II, Schweinfurt - Schweinfurt/DE
  • 12Medcenter Nordsachsen, MedCenter Nordsachsen, 04435 - Schkeuditz/DE
  • 13Praxisnetzwerk Hämatologie Und Internistische Onkologie, Praxis, 53840 Troisdorf - Troisdorf/DE
  • 14Onkologie, Onkozentrum Dresden/Freiberg, 01127 Dresden - Dresden/DE
  • 15Onkologische Praxis Bottrop, Praxis, 46236 Bottrop - Bottrop/DE
  • 16Klinik Mit Schwerpunkt Hämatologie Und Onkologie, Charite, Campus Benjamin Franklin Medizinische Klinik III, 12200 - Berlin/DE
  • 17Koordinationszentrum Klinische Studien, Koordinationszentrum klinische Studien, 06120 Halle - Halle/DE
  • 18Ag Klinische Forschung In Der Onkologie, Martin Luther University of Halle, 06120 Halle - Halle/DE
  • 19Departement For Internal Medicine, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, 20246 - Hamburg/DE

Abstract

Background

TRIBE has shown superiority of adding Oxaliplatin to FOLFIRI / Bev (F. Loupakis, NEJM 2016); STEAM (J. Bendell, ASCO GI 2014) and CHARTA investigate the addition of Irinotecan to FOLFOX + Bev in a randomized Phase II trial.

Methods

7/11 to 12/14 250 patients were randomized to standard FOLFOX / Bev (A) vs. FOLFOXIRI / Bev (B), with dose / schedule as in TRIBE, with exception of 25% dose reductions in cycles 1 and 2 if necessary. Incl.- criteria: ECOG 0-2, ≥ 1 measurable lesion > 1cm. Stratification: ESMO-Group 1,2,3 (Schmoll et. al., Ann Oncol 2012). Treatment-duration: 6 months induction, 12 months maintenance or until progression. Primary Endpoint: Improvement of PFS-rate @ 9 months with p < 0.1 (2-sided, Fisher's-exact test), secondary endpoint: RR- rate, PFS, OS, sec. resection.

Results

241 pts. evaluable (1 not elig., 8 protocol violation); pts. characteristics: m/f: 65%/35%, age 61yrs. (21-82), left/right: left A: 51,5%, B:48,5%; right A: 45%, B: 55%, ECOG 0-1/2: 96% / 4%, ESMO-group 1/2/3: 29%/ 55%/ 16%, Koehne-Score: low/ intermed./high 9% /75%/ 16%; no difference for A vs.B in all subgroups. Primary endpoint was met: PFS-rate @ 9 months of 56% vs. 68% (p= 0,086); median PFS 9,76 vs. 12,0 months, HR 0.77, p = 0.61 (TRIBE-Trial: 9,7 vs. 12,1). Response-rates (A/B): CR 5% vs. 5%, CR + PR 60% vs. 70%, SD 25% vs. 21%, PD 14% vs. 9%. Mets resection: 23% vs. 26%. OS 24.9 vs 27.9 months (prelim.). PFS-Subgroup - analysis did not show significant differences, except left vs. right location: 10.4 vs. 12 months (HR 0.69, p = 0.03). Beyond this, a non-significant improvement was seen in ESMO-Group 3 (HR 0.51), RAS-wt (HR 0.67), Koehne-score High risk (HR 0.58), ECOG 1 (HR 0.69). The QL-Health-Score after induction was slightly reduced in A and improved in B without major changes. Dose-intensity 90% (A vs. B): 39% vs 37%/ 18% vs. 26% / 41% vs. 36%; initial dose-reduction 17% of pts. Toxicity: was low to moderate without major differences between A &B, except grade ¾ diarrhea 12% vs. 16%, neutrophils 14% vs. 20% & GI 12% vs. 20%.

Conclusions

CHARTA reproduces response- & PFS-data of TRIBE and further supports the use of the 4-drug-regimen 1st-line-treatment for most pts.

Clinical trial identification

NCT01321957, First received: March 23, 2011

Legal entity responsible for the study

Martin-Luther-University Halle-Wittenberg

Funding

Roche

Disclosure

All authors have declared no conflicts of interest.