PD-016 - Developmental therapeutics activity portrait in metastatic colorectal cancer (mCRC): Vall d Hebron Institute of Oncology Program

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Drug Development
Colon Cancer
Rectal Cancer
Translational Research
Presenter J. Grasselli
Citation Annals of Oncology (2015) 26 (suppl_4): 101-107. 10.1093/annonc/mdv234
Authors J. Grasselli1, J. Tabernero1, G. Argilés1, M. Alsina1, T. Macarulla2, R. Salazar3, E. Elez1, T. Sauri1, J. Capdevila4, C. Hierro1, F. Salva2, E. Sanz-García2, F. Racca2, A. Azaro1, I. Braña1, M. Ochoa de Olza1, I. Grau1, G. Sala1, J. Rodon5
  • 1Vall d'Hebron Institute of Oncology, Barcelona/ES
  • 2Vall d'Hebron University Hospital, Barcelona/ES
  • 3Institut Català d'Oncologia, L'Hospitalet de Llobregat/ES
  • 4Vall d'Hebron Hospital, Barcelona/ES
  • 5Vall d'Hebron Institute of Oncology (VHIO), Barcelona/ES

Abstract

Introduction

Molecular screening and biomarker enrichment strategies in mCRC trials have demonstrated an impact in treatment benefit and prognosis. Therefore, current clinical research programs are facing two issues: Increasingly tight inclusion criteria and a higher rate of screening failures.

Methods

We analyzed the activity of our colorectal cancer (CRC) and developmental therapeutics programs focusing on the number of clinical trials dissected by design, setting and molecular population selection. Screening and study procedures were also registered to assess a potential added limitation for study entry or a higher screening failure rate.

Results

From 1/2013 to 12/2014, 31 studies were available for mCRC pts at our unit. Among these, 24 (77'41%) were specific per tumor type and 7 (22'59%) recruited for all solid tumors with a specific mCRC cohort. Our 31 clinical trials were comprised by 15, 11 and 5 phase I, II and III respectively and 4, 5 and 22 first, second and refractory setting studies. A biomarker selection was required in 20/31 trials: RAS wild type (6), RAS mutant (mt) (6), BRAF mt (5), CEA overexpression (1), MET overexpression/amplification (1) and PDL-1 overexpression (1). In 24 out of 31 studies (77'42%) it was mandatory archival tumor tissue availability and in 7 of them a fresh tumor biopsy was also an inclusion criteria. We evaluated 837 new-diagnosed CRC pts at our department in this period. Among these, 502 were mCRC pts. A total of 276 pts signed a consent form for any trial in the metastatic setting achieving 211 inclusions (42%): 13'27% in first line, 9'48% in second line and 77'25% in the refractory setting. The screening failure (SF) ratio was 23'55% (65 SFs): 6 pts in first line (9'2%), 11 pts in second line (16'0%) and 48 pts in the refractory setting (73'8%). When dissecting the 48 refractory pts considered SF, 21 pts (43'75%) harbored a BRAF mt (15 pts) or a KRAS G13D mt (6 pts) that could be expected due to the worse prognosis suggested for these populations.

Conclusion

Our work shows the activity of a reference center in drug development for mCRC. Although a 42% of our population is included in a clinical trial at any time point of their evolution, there are still more than a half of patients that do not. Added to clinical features that constitute general exclusion criteria for clinical trials, the molecular selection and the tissue request represent major limiting factors. Also, most trials at our site are focused on the refractory setting in a heavily pretreated population that translates in a higher rate of SF particularly in studies that target populations with worse prognosis. Hence, an early molecular characterization is strongly recommended to design an optimal therapeutic strategy, save time for patient identification and inclusion in clinical trials and decrease rate of failures.