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Published on 2 November 2009

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Highlights of the Joint ECCO 15–34th ESMO Multidisciplinary Congress

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Offering a unique platform to embrace all oncology specialities, the joint congress reflects the mission of both societies to promote a multidisciplinary focus on oncology for the benefit of patients

M Garassino
D Schrijvers
B Zakotnik

With a strong commitment to unite oncology in Europe, the European CanCer Organisation (ECCO) and the European Society for Medical Oncology (ESMO) joined forces to combine the two leading educational opportunities in European oncology ” the ECCO and ESMO congresses” every other year. Offering a unique platform to embrace all oncology specialities, the joint congress reflects the mission of both societies to promote a multidisciplinary focus on oncology and uphold the right of all patients to the best treatment and care available. The first joint ECCO 15 34th ESMO Multidisciplinary Congress took place in Berlin, Germany, 20–24 September 2009 and attracted a record-breaking number of over 15,000 delegates from all over the world.

Thanks to the efforts of Alexander Eggermont, ECCO President and 2009 Congress President, Jose Baselga, ESMO President, Chris Twelves, Co-Scientific Chair (ECCO), Fortunato Ciardiello, Co-Scientific Chair (ESMO), the Vice-Chairs: Rene Bernards- Basic Science (EACR ), Vincent Gregoire-Radiotherapy (ESTRO), Cornelis van de Velde- Surgery (ESSO), Peter Schlag, National Organising Committee Chair, as well as the dedication and hard work of leading experts, the Scientific Committee assembled a very in-depth and comprehensive programme. In addition to the many excellent educational initiatives across disciplines that were developed truly to promote the importance of multidisciplinarity in oncology, the meeting’s strength was revealed in an expanded number of Presidential sessions that discussed key issues in cancer research and served as an ideal platform for presentation of the latest scientific discoveries by the cancer research community. This report discusses the highlights of the congress scientific programme.

Timothy Maughan of Cardiff University, Section of Clinical Oncology and Palliative Medicine, Cardiff, United Kingdom presented results of intermittent versus continuous oxaliplatin-based combination chemotherapy tested in a randomised non-inferiority trial (MRC COIN) in 1,630 patients with advanced colorectal cancer. Median overall survival on continuous treatment was 15.6 months versus 14.3 months on intermittent treatment. The primary analysis of the cetuximab comparison was in the cohort of WT KRAS patients. Tumour samples from 1305 (80%) patients were available for KRAS analysis. WT KRAS patients numbered 724 (56%), while 561 (43%) had a KRAS mutation. Patients in the second arm experienced significantly greater grade 3/4 diarrhoea, skin rash, lethargy, hand”foot syndrome, and hypomagnesaemia, but significantly less grade 3/4 peripheral neuropathy. The researchers observed no evidence of any differences in treatment-related or 60-day all cause mortality between the two arms. Presenting results, Prof Maughan said that the estimated difference in favour of continuous treatment needs to be balanced against the reduced toxicity observed with intermittent treatment.

Hans-Joachim Schmoll, of University Clinic Halle, Germany presented results of the study on first efficacy findings from a randomised phase III trial of capecitabine + oxaliplatin (XELOX) versus bolus 5-FU/LV for stage III colon cancer. 1,886 patients were enrolled (median follow up 57 months) and were  evaluable for the primary study endpoint, disease-free survival, which was significantly superior for XELOX at 3 and 4 years (71% vs. 67%; 68.4% vs. 62.3% respectively, p=0.0045). Overall survival data are currently immature.

Gunther G Steger of Medical University of Vienna, Department of Internal Medicine, Division of Oncology, Vienna, Austria reported a randomised phase III study comparing epirubicin, docetaxel, and capecitabine (EDC) to epirubicin and docetaxel (ED) as neoadjuvant treatment for early breast cancer. The primary aim of the study was an improvement of the pathological complete response rate. 512 patients were eligible for toxicity and efficacy. In the intention-to-treat analysis there was no significant difference in the incidence of serious adverse events. In the EDC arm significantly more patients had documented a pathological complete response (23.8% vs. 15.2%; p=0.036) despite the fact that significantly less patients completed the scheduled 6 cycles (EDC: 75% vs. ED: 97%; p<0.0001) mainly because of capecitabine-induced side effects.

Veronique Dieras of Institut Curie, Department of Medical Oncology, Paris, France presented results of efficacy in patient subgroups in RIBBON-1, a randomised, double-blind, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer. A total of 1,237 patients were enrolled. Addition of bevacizumab improved progression-free survival (Capecitabine: placebo 5.7 months, bevacizumab 8.6 months; p=0.0002; Taxanes + Anthracyclines: placebo 8.0 months, bevacizumab 9.2 months; p<0.0001). In pre-specified subgroups, hazard ratios favoured the bevacizumab arms of the respective chemotherapies.

José Baselga of Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain showed results of a double-blind, randomised phase 2b study (SOLTI-0701) evaluating the efficacy and safety of sorafenib compared to placebo when administered in combination with capecitabine in 229 patients with locally advanced breast cancer. By investigator assessment, the median progression-free survival of the capecitabine-placebo versus the capecitabine- sorafinib combination was 4.1 months versus 6.4 months (p=0.0006). Toxicities of grade 3 or 4 included hand-foot skin reaction, diarrhoea, dyspnoea, neutropenia and mucositis.

Alison Stopeck of University of Arizona Cancer Center, Hematology and Oncology in Tucson, USA presented results of a randomised phase III study comparing denosumab versus zoledronic acid for the treatment of breast cancer patients with bone metastases. Denosumab significantly delayed the time to first on-study skeletal related event (SRE) compared with zolendronic acid (p=0.01) in this 34-month study. The median time to first on-study SRE was not reached for denosumab, and was 806 days for zolendronic acid. Denosumab also significantly delayed the time to first and subsequent on-study SRE (multiple event analysis) compared with zolendronic acid (p=0.001).

KRAS as a predictive biomarker
Three important abstracts confirmed the importance of KRAS as a predictive biomarker of anti-epidermal growth factor receptor monoclonal antibodies in the 1st-line metastatic colorectal cancer (mCRC ) in combination with chemotherapy.

Marc Peeters, MD, Professor of Digestive Oncology at University Hospital in Ghent, Belgium presented a randomised phase III study of panitumumab with FOLFIRI versus FOLFIRI alone as second-line treatment in patients with mCRC . A total of 1,186 patients were randomised. For patients with wild type (WT) KRAS, median progression-free survival was 5.9 months and 3.9 months with and without panitumumab (p=0.004); median overall survival was 14.5 months and 12.5 months with and without the monoclonal antibody; and response rate (by blinded central review) was 35% and 10%. There was no difference in progression-free and overall survival or response rate among patients with mutated KRAS .

Jean-Yves Douillard, director of Clinical and Translational Research, Medical Oncology Branch, University Hospital, Ghent, Belgium presented results of the randomised phase III study of panitumumab with FOLFOX4 compared to FOLFOX4 alone as first-line treatment for metastatic colorectal cancer (PRIME trial). A total of 1,183 patients were randomised. For patients with WT KRAS , median progression-free survival was 9.6 months for the panitumumab combination and 8.0 months for FOLFOX alone (p=0.0234). For patients with mutated KRAS median progression-free survival was 7.3 months for the panitumumab combination and 8.8 months for FOLFOX alone (p=0.0227).

Non-small-cell lung cancer
Three presentations focused on patients with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations underlying the growing body of evidence of genotyping tissue for taking clinical decisions.

Junji Tsurutani on behalf of the West Japan Oncology Group (WJOG) presented results of a comparison of gefitinib versus cisplatin plus docetaxel for patients with advanced or recurrent NSCLC harbouring activating mutation of the EGFR gene. Two hundred patients were randomised showing that gefitinib significantly prolonged response rate (56.3% vs. 25.3%) and progression- free survival (9.2 months vs. 3.6 months; p<0.001) compared to chemotherapy. Haematological toxicity was more pronounced in the chemotherapy arm while skin rash and liver function test disturbances were more seen in the gefitinib arm.

Mark Kris of Memorial Sloan-Kettering Cancer Center, New York, USA found similar results and presented pooled results of the four main studies comparing gefitinib (ISEL, V-15-32-INTEREST-IPASS ) versus placebo or chemotherapy in 1,006 patients with EGFR mutations. In EGFR-mutation negative patients, overall response rate (OR) was 3% while in EGFR-mutation positive patients overall response rates were 30% for docetaxel alone and 47% for carboplatin/paclitaxel. For mutation-negative patients, ORs were 9% with docetaxel alone and 24% with carboplatin/paclitaxel. In every study, OR was numerically better for gefitinib than comparator in EGFR-mutation positive patients, and similar or poorer than comparator in EGFR-mutation negative patients: in patients with EGFR mutations, OR with gefitinib was 71% when used initially and ranged from 38–67% in studies where gefitinib was given after chemotherapy. A trend similar to OR was observed for progression-free survival or time to treatment failure, with longest median values in gefitinib- treated EGFR-mutation positive patients (range 7–11 months).

Taken together, these analyses indicate that efficacy of gefitinib in EGFR-mutated patients is consistent across all lines and ethnicities (Asians vs. non-Asians) and stresses the importance of the knowledge of EGFR mutation status when selecting a treatment with tyrosine kinase inhibitors regardless of line of therapy.

The treatment of locally advanced head and neck cancer underwent recently important changes with the introduction of new radiotherapy techniques and the addition of chemotherapy or targeted agents to radiotherapy. These techniques can produce better treatment outcomes in terms of local control and survival but add higher acute and late toxicity. However, longterm results of newer treatment modalities in relation to outcome are still scarce.

Sofia Rivera of the Centre Georges-François Leclerc, Radiation Oncology, Dijon, France looked at the recurrence patterns in 50 patients with squamous cell carcinoma of the head and neck (SCHN) treated with intensity-modulated radiotherapy (IMRT) with or without chemotherapy. At a median follow-up of 22 months, 14 loco-regional failures (persistent disease or relapse) were observed. Five were in-field, five were marginal, and four occurred out-field. Two of those marginal failures had received more than 95% of the prescribed dose on more than 95% of the failure gross tumour volume (GTVf). The 2-year overall survival, local disease-free survival and loco-regional disease-free survival rates were 73%, 78% and 72%, respectively. The authors concluded that despite a high rate of locoregional and overall disease-free survival, target volume delineation and definition of margins should be analysed with accuracy because local failure remains a major issue.

Dr Chris Nutting from the Head and Neck Unit, Royal Marsden NHS Trust presented results of the PARSPORT trial. They showed that sparing the salivary glands through the use of IMRT significantly reduced the incidence of xerostomia in patients with pharyngeal tumours. In this trial two radiotherapy delivery methods were compared in the treatment of 94 patients with pharyngeal tumours. After a median follow-up of 31.9 months, 12–month LENT-SOMA ≥G2 xerostomia scores  were observed in 74% of radiotherapy and 40% of IMRT patients (p=0.005). Corresponding values at 18 months were 71% and 29% (p=0.004). On the RTOG scale, 12-month ≥G2 xerostomia was reported in64% radiotherapy versus 41% IMRT patients (p=0.06). The 18-month incidence was 81% for radiotherapy versus 20% for IMRT (p<0.001). Acute radiotherapy related ≥G2 fatigue was more prevalent in the IMRT group (76% vs. 41%; p=0.001). No differences in acute mucositis or pain scores were seen. At 12 months, no statistically significant differences were seen in other late toxicities. No differences were observed between overall survival and loco-regional control rates.



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