The EORTC Gastrointestinal (GI) Tract Working Group has put a particular focus in expanding our knowledge about genetic, epigenetic and immunologic backgrounds of gastrointestinal tumor diseases.
We are therefore conduction research meetings with a particular focus on translational questions. The first of this kind was done in Paris, France in 2011 and was about molecular diagnostics in GI cancer. The second was done in Dresden in 2013. The topic was “target identification” for better drug therapies in colorectal and gastric cancer. The newest edition was done in Mainz, Germany, in November 2014 and focused on “immuno-oncology” in GI tumors.
From these initiatives we try to develop a more intense preclinical to clinic interaction and an integration of early drug development into our clinical trial portfolio.
All new clinical studies that are now developed by our group contain an intensive correlative research program. For each protocol we have separate “translational steering committee”, ensuring that current aspects of tumor biology are being investigated with appropriate contemporary technology.
Since extensive screening is necessary to conduct trials in subgroups of CRC, a screening platform, SPECTAColor, is being initiated with the strong financial support of Alliance Boots. Patients presenting with metastatic CRC (or high risk stage III tumors) at the participating centers will consent that their tumor material is centrally characterized for molecular markers by a standardized method. Depending on the results of this screening, therapeutic clinical trials will be offered to the patients fulfilling the molecular inclusion criteria. The screening platform requires a central pathology service unit for central quality control and DNA and RNA extraction from the tumor, and this unit will work closely with the virtual tissue bank at EORTC Headquarters. The activation procedures are presently ongoing.
Perioperative chemotherapy has a proven benefit in localized gastric cancer and esophago-gastric junction adenocarcinoma, but only about 20% of patients achieve a major histologic response from neoadjuvant chemotherapy. To improve upon this, The GI Group in collaboration with the EORTC Imaging Group propose an imaging sub-study aimed at validating the sensitivity and specificity of the FDG-PET (18F-fluorodeoxyglucose positron emission tomography) based early response test in a multicenter study. Early metabolic response evaluation by FDG-PET allows for an accurate prediction of histo-pathologic response during neoadjuvant chemotherapy, and PET imaging has been shown to have some predictive value in esophago-gastric cancer treated with neoadjuvant chemotherapy, but these have not been validated in a multicenter setting. Such a study is presently in preparation inside of the Group.
A retrospective analysis of clinical data from 342 patients who participated in EORTC Trial 40983 (EPOC) revealed that perioperative FOLFOX seems to benefit a particular subset of patients with liver metastases from colorectal cancer. These results published by Sorbye et al. (Ann of Surg 2012;255(3):534-539) were cited as a “notable advance” in Clinical Cancer Advances 2012: ASCO’s Annual Report on Progress Against Cancer.
EORTC trial 40091 (BOS2) aims to assess the value of the addition of bevacizumab or panitumumab to FOLFOX as perioperative treatment for wild type KRAS colorectal cancer patients metastatic to the liver deemed to be resectable.
The BOS2 imaging subprotocol’s primary endpoint is to examine the NPV of PET assessed tumor FDG uptake response after one course of preoperative chemotherapy on the outcome of neo-adjuvant therapy, measured by structural, radiologically-assessed response rate.
EORTC trial 40983 (EPOC) has been re-evaluated for long term results, and an abstract was presented at ASCO 2012. TR is in progress.
For EORTC trial 1203 (INtegratioN of trastuzumab, with or without pertuzumab, into periOperatiVe chemotherApy of HER-2 posiTIve stOmach caNcer: the INNOVATION-TRIAL) an accompanying FGD-PET early response assessment is under development.
The ultimate goal is to enrich patient groups how have a realistic chance for a benefit from a given treatment intervention by getting early information about “response or non-response” during drug interventions.
Management of elderly patients
Based on the clinical and scientific need, we have activated a phase II trial in frail patients with metastatic colorectal cancer comparing 5Fu/LV alone and in combination with cetuximab. This trial is a collaborative effort between the EORTC Cancer in the Elderly Task Force and the GI Group and can serve as a pilot protocol in which we integrate specific elderly related tools. It opens also the opportunity to generate scientific data in a population that in most cases is excluded from clinical trials.
Protocols activated in 2012-2014
EORTC trial 40071: Effectiveness of first line treatment with lapatinib and ECF/X in metastatic gastric cancer according to HER2 and EGFR status: a randomized phase II trial. About 480 patients with adenocarcinoma of the stomach or eso-gastric junction who were not amenable to curative surgery and who did not receive prior palliative CT will be screened centrally for HER2/EGFR1 by FISH and IHC. Patients are enrolled into one of two strata: HER2 FISH- and IHC 2/3+, or HER2 IHC 0/+ and EGFR1 FISH+ or IHC 2/3+.
EORTC trial 22114: Trial of preoperative therapy for gastric and esophagogastric junction adenocarcinoma. A randomized phase II/III trial of preoperative chemotherapy for resectable gastric cancer (TOP GEAR).
EORTC trial 40091: Randomized phase II trial evaluating the efficacy of FOLFOX alone, FOLFOX plus bevacizumab and FOLFOX plus panitumumab as perioperative treatment in patients with resectable liver metastases from wild type KRAS and NRAS colorectal cancer.
EORTC trial 40085: Treatment of patients with KRAS and NRAS wild type advanced colorectal cancer with 5-fluorouracil (5-FU) or 5-FU plus an Epidermal Growth Factor Receptor inhibitor (cetuximab) based on a Comprehensive Geriatric Assessment.
EORTC trial 40101/AIO-STO-0309: An open-label, randomized phase III trial of cisplatin and 5-fluorouracil with or without panitumumab for patients with nonresectable, advanced or metastatic esophageal squamous cell cancer (ESCC)(POWER). This Intergroup Clinical Study in cooperation with the AIO-Studien-gGmbH is active recruiting with 118 of 300 randomized patients by December 2014. Germany (24 sites, 92 pt.), Spain (8 sites, 12 pt.), Belgium (5 sites, 7 pt.), Austria (2 sites, 5 pt.) and Israel (3 sites, 2 pt.). Other centers are welcome to join https://clinicaltrials.gov/ct2/show/NCT01627379 and http://www.power-studie.de
The GI Group and the European Association for the Study of the Liver (EASL) published joint Clinical Practice Guidelines on the management of hepatocellular carcinoma (HCC) (J Hepatology 2012;56(4):908-943; Eur J Cancer 2012;48(5):599-641). These EASL-EORTC guidelines define the use of surveillance, diagnosis and therapeutic strategies recommended for patients with HCC.
As a result of the EORTC-St. Gallen meeting being organized in March 2012, the group published specific guidelines on “Highlights of the EORTC St. Gallen International Expert Consensus on the primary therapy of gastric, gastroesophageal and oesophageal cancer – differential treatment strategies for subtypes of early gastroesophageal cancer.” (Lutz M, et al. Eur J Cancer. 2012 Nov;48(16):2941-53)
A consensus paper on primary treatment of rectal cancer, resulting from the EORTC St. Gallen meeting being organized in March 2014 is in preparation.
The EORTC GI Tract cancer working group has started to organize in cooperation with the foundation St.Gallen Oncology Conferences (SONK) a biannual education and consensus meeting: the St. Gallen EORTC Gastrointestinal Cancer Conference.
The first meeting of this kind was the 1st St. Gallen Conference on Gastrointestinal Cancer“, 22-24 March 2012 with a focus on early gastric cancer. This was followed by the 2nd St. Gallen Conference on Gastrointestinal Cancer“, 6-8 March 2014 with a focus on early rectal cancer. We are looking forward to the 3rd edition of this meeting, 10-12 March 2016, topic to be determined.
We are supporting young investigators from medical oncology, radiation oncology, surgical oncology, pathology, imaging or basic research to join our group. They can bring in new ideas and use the EORTC databases. The get support from our research teams and statistics department for bringing forward their research ideas.
Young investigators are supported by a competitive grant, they can apply for on an annual basis. Our currently supported research fellows are Dr. Lilian Schwarz from the Surgery Department in Rouen, France and Dr. Gertraud Stocker from the University Cancer Center in Leipzig, Germany.