The Joint ECCO 15-34th ESMO Multidisciplinary Congress: A Unified Approach Marking a Meeting of “Firsts” September 20-24, 2009
Berlin, Germany
By: Chris Twelves, MD, PhD, Co-Scientific Chair (ECCO);
Fortunato Ciardiello, MD, PhD, Co-Scientific Chair (ESMO)
Building on the successes of the previous European CanCer Organisation (ECCO) and European Society for Medical Oncology (ESMO) meetings, this first jointly organised Congress marked an occasion of many “firsts”—a new phase and a new day for European oncology.
With a record attendance of almost 15,000 participants, 26 different tracks devised created by more than 100 leading experts, 600 invited speakers, and more abstracts and late-breaking data presented than ever before—and perhaps more importantly, the views of every discipline put together in a truly multidisciplinary forum—enriched attendee knowledge and represented an important milestone in progressing oncology as a whole.
The potentially groundbreaking presentation by Paul B. Chapman, MD, of Memorial Sloan-Kettering Cancer Center, and colleagues reported updated results of the phase I trial of calculators PLX4032, an oral selective inhibitor of V600E mutant BRAF kinase. In the dose-escalation phase, 55 patients were treated. At the maximum-tolerated dose, dose-limiting toxicities were rash, fatigue, and arthralgias, all of which resolved on drug discontinuation. Several patients also developed squamous cell carcinomas (SCC) of the skin. Of the 26 patients treated at doses of 240 mg or higher twice daily, which achieved drug exposure in terms of plasma AUC that are potentially therapeutic, 16 had melanomas with the BRAF mutation, of whom 11 experienced a response to treatment. The update described the expanded cohort of 31 patients treated at the maximum-tolerated dose of 960 mg twice daily, all of whom had V600E mutant BRAF melanomas.
Treatment was again well tolerated, although the incidence of SCC was 23%. There were 18 partial responses and one complete response, giving an objective response rate of 70%; only one patient had progressive disease as the best response. Objective responses were seen at all tumor sites and confirmed by positron emission tomography (PET) scan on day 15. Sixty percent of patients with melanoma have cancers with the V600E BRAF mutation, so this high level of activity is potentially applicable to the majority of patients with malignant melanoma. Further trials are already underway or planned, including phase II and III studies in V600E BRAF mutant melanoma.
Another early trial that has potential to change practice was presented by José Baselga, MD, of Hospital Vall D’Hebron, Barcelona, Spain, and colleagues. Sorafenib is well known as a potent multikinase inhibitor with both anti-angiogenic and anti-proliferative activity that is used in both renal and hepatocellular carcinoma. The SOLTI-0701 study evaluated sorafenib in combination with capecitabine in a double-blind, randomized, placebo-controlled phase II study of 229 women with advanced breast cancer. Eligibility was limited to women with HER2-negative tumors who had received only one prior chemotherapy regimen for advanced or metastatic disease. In the control arm patients received capecitabine 1,000 mg orally twice daily for 14 days repeated every 21 days; those in the experimental arm also received a sorafenib dose of 400 mg orally twice daily continuously. The primary endpoint was progression-free survival (PFS) according to investigator assessment. PFS was a median of 6.4 months on the combination arm compared to 4.1 months with capecitabine alone (hazard ratio [HR] 0.576, p=0.0006); response rates were 38% and 31%, respectively.
Treatment was well tolerated with no unexpected side effects observed. This represents the first clear demonstration of the benefit of adding sorafenib to chemotherapy in the treatment of metastatic breast cancer.
Hans-Joachim Schmoll, MD, PhD, of Martin-Luther-Universitaet, Halle, Germany, on the behalf of the NO16968/Xeloxa study, reported the first efficacy results from a large multicenter randomized phase III trial in which capecitabine in combination with oxaliplatin was assessed as adjuvant treatment in stage III operable colorectal cancer as compared to standard bolus intravenous 5-FU/folinic acid treatment. Patients received 6 months of either treatment after potentially curative surgery. Almost 1,900 patients were enrolled in this study.
After a median follow-up of almost 5 years, the results showed the superiority of the capecitabine-oxaliplatin combination as demonstrated by a statistically significant increase in disease-free survival at 3 years, the study’s primary endpoint (HR 0.80, p=0.0045). The results of this study demonstrate that fluoropyrimidine-oxaliplatin combinations (either with infusional 5-FU/folinic acid, as demonstrated by the MOSAIC study, or with oral capecitabine, as demonstrated by this study) are valid options for adjuvant treatment of stage III colorectal cancer.
An important report that will affect the treatment choices for patients with KRAS wild-type metastatic colorectal cancer comes from the efficacy results of the CRYSTAL randomized phase III study of standard folinic acid, fluorouracil, and irinotecan (FOLFIRI) regimen compared to FOLFIRI plus the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in the first-line treatment of metastatic colorectal cancer.
Following the initial report which was published earlier this year in the New England Journal of Medicine, in which data evaluating the primary endpoint, PFS, were presented in the intention-to-treat non-selected patient population and in a 45% subgroup of patients in which KRAS gene status was determined, Eric Van Cutsem, MD, PhD, of the University of Leuven, Belgium, and colleagues have reported in Berlin the final mature data on 89% of the 1,200 patients in which KRAS gene status was determined in terms of the primary endpoint (disease-free survival) and also in terms of the secondary endpoints (response rate and overall survival).
These results confirmed a significant reduction in the risk of disease progression in patients with KRAS wild-type metastatic colorectal cancer treated with cetuximab plus FOLFIRI as compared to FOLFIRI (HR 0.70, p=0.0012), as well as a significant increase in response rate (odds ratio 2.1, p<0.0001). Moreover, and more importantly for clinical practice, survival—although it was a secondary endpoint and although approximately 25% of patients in the FOLFIRI alone arm received cetuximab as part of second-line treatment—was statistically improved in patients with KRAS wild-type tumors treated with the combination of cetuximab and chemotherapy. Median overall survival was 23.5 months for patients receiving cetuximab plus FOLFIRI compared 20.0 months for those who received FOLFIRI alone (HR 0.8, p=0.0094). These are the first results to show a survival advantage in adding cetuximab to standard doublet chemotherapy in this disease setting.
ECCO 15-ESMO 34 participants returned home with more information, new ideas, new collaborations, and a vision to move the field forward. The united European oncology community is ambitious, and has the plans and the strength to make the difference.
The next joint ECCO 16 and 36th ESMO Multidisciplinary Congress will take place in Stockholm, Sweden, on September 23-27, 2011.
Online Exclusive - Feb. 3, 2010
ACRIN 2009 Annual Meeting: Ten Years of Advancing Imaging Research September 29-October 3, 2009
Arlington, Virginia
By: Mitchell D. Schnall, MD, PhD
ACRIN Network Chair
University of Pennsylvania
The 2009 American College of Radiology Imaging Network (ACRIN) Annual Meeting, held September 29-October 3 in Arlington, Virginia, was an exciting assembly of ACRIN scientific leaders, staff, and members of the scientific community who gathered to reflect on past ACRIN scientific achievements and to discuss future scientific goals and objectives. The meeting included individual sessions for each of the nine ACRIN Scientific Committees, including the ACRIN Pennsylvania Trials Network, Experimental Imaging Sciences, and the newly established Cardiovascular and Neurosciences committees. Each session was a valuable opportunity for committee members to review active protocols and to discuss new and upcoming concepts.
The first Plenary Session of the Annual Meeting was reserved for presentations by ACRIN leadership and selected principal investigators. ACRIN Network Chair Mitchell D. Schnall, MD, PhD, of the Hospital of the University of Pennsylvania, presented “The State of ACRIN: 10 Years Progress,” in which he outlined ACRIN’s primary scientific objectives, the organizational structure, ten years of ACRIN accomplishments, past and future challenges, and scientific progress. Constantine A. Gatsonis, PhD, of Brown University and Director of the ACRIN Biostatistics Center, delivered an ACRIN Biostatistics Center update presentation. Five ACRIN principal investigators provided presentations on their respective studies.
Gerald D. Dodd III, MD, of the University of Denver and ACRIN 6673 Study Principal Investigator, presented “Preliminary Results of ACRIN 6673: Multicenter Feasibility Study of Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in Cirrhotic Patients,” which reported preliminary study site data based on analysis of local site data generated by the 14 participating sites. Central reader data associated with this trial is in analysis now and publication of results is expected in early 2010.
Timothy J. Mosher, MD, of Penn State University Milton S. Hershey Medical Center and ACRIN PA 4001 Study Principal Investigator, presented “Reproducibility of Measures of Cartilage Morphometry, T1rho, and T2 in a Multi-Center Trial (ACRIN PA 4001).” Dr. Mosher’s presentation noted that there is substantial clinical impact of osteoarthritis, which has become a pending epidemic, with an estimate that 60 million Americans will be diagnosed with this disease by 2020. These statistics were a large part of what motivated the development of this trial (Health Care and Aging Studies Branch, Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, April 26, 2005). There is a need for objective biomarkers of cartilage damage and response to treatment, and therefore, the goal is to move from symptom-focused to disease-focused treatment. This study’s purpose is to determine reproducibility of magnetic resonance imaging (MRI) biomarkers for cartilage injury in a multi-center trial.
Jeff L. Fidler, MD, of Mayo Clinic and ACRIN 6664 Principal Investigator, presented “CTC Detection of Flat Adenomas in the National CTC Colonography Trial (ACRIN 6664),” a secondary ACRIN 6664 circulating tumor cells (CTC) study which will provide further data regarding controversial issues related to flat adenomas, including sensitivity of CTC using a restricted criteria; prevalence in the National CTC Trial screening population; and incidence of advanced histology.
Constance D. Lehman, MD, PhD, of the University of Washington and ACRIN 6657 Principal Investigator, presented “Comparison of MRI and Mammography for Evaluation of Residual Disease Following Neoadjuvant Chemotherapy for Locally-Advanced Breast Cancer (ACRIN 6657).” Dr. Lehman outlined the study’s purpose and imaging aims, which include the evaluation of MRI’s ability to predict three-year disease-free survival (DFS), the ability of MRI measured early in treatment to predict response to treatment, and the ability of MRI to assess residual disease post-therapy, prior to surgery.
Dr. Mosher (ACRIN PA 4001), Dr. Fidler (ACRIN 6664) and Dr. Lehman (ACRIN 6657) will each be presenting abstracts on their respective ACRIN trials at the 2009 Radiological Society of North America Annual Meeting (RSNA), November 29-December 4, in Chicago, Illinois.
Denise R. Aberle, MD, of the University of California, Los Angeles, David Geffen School of Medicine, ACRIN Network Co-Deputy Chair, and ACRIN National Lung Screening Trial (NLST) Study Principal Investigator, presented “Minority Accrual into the National Lung Screening Trial (ACRIN 6654).” Dr. Aberle’s research recognized that there is limited minority participation in prevention research which impacts generalizability within health care delivery and which equitably distributes risks and benefits of clinical trials. Barriers to overcome in minority recruitment include raising awareness of clinical trials among minority populations and creating opportunities for participation in clinical trials. As a strategic method to recruit minorities, this trial incorporated the use of a minority recruitment plan to target accrual of minority patients.
The focus of the second Plenary Session at the ACRIN Fall Meeting was Dynamic Contrast Enhanced (DCE) MRI. Presenters consistently cited the use of DCE-MRI as having many benefits, but there are many challenges involved with its use and implementation into clinical trials. ACRIN invited guest speakers to present on various aspects of this imaging method. Peter L. Choyke, MD, of the National Cancer Institute, presented “Potential for DCE-MRI as an Angiogenesis Marker” in which he summarized how angiogenesis is an important target for cancer therapy, and noted that although DCE-MRI is difficult to integrate into multi-institutional clinical trials, it is widely available.
Edward F. Jackson, PhD, of M. D. Anderson Cancer Center, presented “Challenges in Quantification of DCE-MRI.” Among the general MRI quantification challenges that were discussed were varying measurement results between vendors and centers; DCE-MRI quantification challenges include data acquisition, data processing, quality control, and vendor-specific and multicenter trial issues. Edward Ashton, PhD, of VirtualScopics, Inc., presented “Approaches to Modeling and Implementation of DCE-MRI in Treatment Trials,” which included a brief summary of VirtualScopics’ experience using DCE-MRI in more than 30 phase I/II clinical trials that demonstrated less than 10% reproducibility and less than 5% data loss rate. Daniel P. Barboriak, MD, of Duke University Medical Center, presented “Implementing DCE-MRI for Evaluation of Brain Tumors in Multi-Center Clinical Trials: Meeting the Challenges.” These challenges include ensuring that techniques are kept simple, incorporating automated image checking, and communicating and providing feedback to technologists. The ACRIN Imaging Core Laboratory was listed as an ideal organization to assist in addressing DCE-MRI implementation challenges for evaluating brain tumors. Each of these presentations on DCE-MRI provided insightful information for ACRIN investigators to consider for imaging in clinical trials.
New at the 2009 ACRIN Annual Meeting was the combination of the Informatics Committee and Imaging Core Laboratory session. This half-day program featured presentations from Andrew Buckler, MS, of Buckler Biomedical LLC, who provided an introduction to the Quantitative Imaging Biomarkers Alliance (QIBA); Richard L. Wahl, MD, of Johns Hopkins University, Director of Nuclear Medicine/Positron Emission Tomography (PET), and Vice Chair of New Technology and Business Development at the Russell H. Morgan Department of Radiology and Radiological Science, who presented “Evolving Considerations for PET Response Criteria in Solid Tumors”; and an overview of Core Laboratory activities by ACRIN Deputy Co-Chair and Chair of the ACRIN PET Core Laboratory, Barry Siegel, MD, of Washington University School of Medicine; and an update on new laboratory software and hardware tools by ACRIN Core Laboratory Operations Administrator Mehdi Adineh, PhD.
This year’s ACRIN Annual Meeting was an impressive mix of scientific discussion and organizational camaraderie, which will help in providing a solid foundation for another successful ten years of imaging research.
