599P - Early tumor shrinkage (ETS) for the prediction of efficacy in metastatic colorectal cancer (mCRC): post-hoc analysis from an irinotecan-based random...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Clemens Giessen
Authors C. Giessen1, R. Laubender2, S. Stintzing3, L. Fischer von Weikersthal4, D. Quietzsch5, U. Vehling-Kaiser6, D. Oruzio7, H. Lambertz8, A. Schalhorn1, V. Heinemann9
  • 1Department Of Medical Oncology And Comprehensive Cancer Center, University of Munich, 81377 - Munich/DE
  • 2University Of Munich, Institute of Medical Informatics, Biostatistics, and Epidemiology, 81377 - München/DE
  • 3Hämatologie Und Onkologie, University of Munich, 81377 - Munich/DE
  • 4Department Of Medical Oncology, Klinikum St. Marien, Amberg/DE
  • 5Department Of Medical Oncology, Klinikum Chemnitz, Chemnitz/DE
  • 6Onkologische Schwerpunktpraxis, Onkologisches und Palliativmedizinisches Netzwerk Landshut, 84028 - Landshut/DE
  • 7Ii. Medizinische Klinik, Klinikum Augsburg, Augsburg/DE
  • 8Zentrum Fuer Innere Medizin - Onkologie, Klinikum Garmisch-Partenkirchen, DE-82467 - Garmisch-Partenkirchen/DE
  • 9Dept. Of Medicine Iii, University of Munich, 81377 - Munich/DE

Abstract

Background

Early tumor shrinkage (ETS) has been highlighted as a favorable prognostic factor related to progression-free survival (PFS) and overall survival (OS) in cytotoxic chemotherapy with or without cetuximab. We investigated ETS ≥20% and <20% in an irinotecan-based randomized phase III trial for first-line treatment for metastatic colorectal cancer.

Material and methods

Data from a randomized phase III study comparing FUFIRI vs. mIROX in 479 pts were evaluated. ETS has been defined as at least 20% shrinkage between the sum of baseline diameters (RECIST) and the first remission control imaging according to Piessevaux et al. As in our study one cycle consisted in 50 days of treatment our time interval was 7.2 weeks. ETS assessment was possible in 201 pts. PFS and OS for ETS ≥ 20% and <20% pts were calculated. Additionally, linear regression for modeling of the absolute tumor shrinkage and Cox regression for OS were estimated.

Results

Baseline characteristics between ETS ≥20% and <20% were comparable, except for median tumor diameter (ETS ≥20% 81.5mm at baseline and 47.0 mm at day 50 vs. ETS <20% 68.0 mm at baseline and 72.0mm at day 50). When compared to pts with ETS <20% (n = 107), patients with ETS ≥20% (n = 94) had a favorable PFS (9.9 vs. 6.1 mo, p = 0.001) and OS (27.5 vs. 17.8 mo, p = 0.001). While ETS is usually indicated as a percentage, measurement of baseline tumor diameters relates to the absolute magnitude of tumor shrinkage. Pts with ETS <20% were subclassified in pts with “minor shrinkage”, (19–0%; n = 65) (PFS 8.4 mo, OS 21.6 mo), pts with “numerical tumor progression” (any increase) at 7 wks (n = 36; PFS 4.0 mo, OS 15.3 mo), and pts with “new target-lesions” (n = 6; PFS 2.2, OS 7.6). Linear regression of the absolute shrinkage on the baseline tumor diameter revealed that with each cm increase in baseline tumor diameter, mean absolute shrinkage increases, namely by 0.354 cm (p < 0.001). Cox regression for OS using absolute tumor shrinkage indicated a hazard ratio of 0.923 (95%C.I. 0.878-0.971; p = 0.002)

Conclusion

In this irinotecan-based study the presence of ETS ≥20% was associated with a significant benefit in PFS and OS. Pts with ETS <20% were found to be a heterogeneous group consisting of pts with minor shrinkage, progressive disease, and new lesions. Baseline tumor diameters had a significant impact on the magnitude of shrinkage.

Disclosure

C. Giessen: Travel support: Roche.

S. Stintzing: honoraria and financial support for research, Merck Serono.

All other authors have declared no conflicts of interest.