Browsing by Author "Van Cutsem, E"
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- ESMO consensus guidelines for the management of patients with metastatic colorectal cancerPublication . Van Cutsem, E; Cervantes, A; Adam, R; Sobrero, A; Van Krieken, J H; Aderka, D; Aranda Aguilar, E; Bardelli, A; Benson, A; Bodoky, G; Ciardiello, F; D'Hoore, A; Diaz-Rubio, E; Douillard, J-Y; Ducreux, M; Falcone, A; Grothey, A; Gruenberger, T; Haustermans, K; Heinemann, V; Hoff, P; Köhne, C-H; Labianca, R; Laurent-Puig, P; Ma, B; Maughan, T; Muro, K; Normanno, N; Österlund, P; Oyen, W J G; Papamichael, D; Pentheroudakis, G; Pfeiffer, P; Price, T J; Punt, C; Ricke, J; Roth, A; Salazar, R; Scheithauer, W; Schmoll, H J; Tabernero, J; Taïeb, J; Tejpar, S; Wasan, H; Yoshino, T; Zaanan, A; Arnold, DColorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
- Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical TrialsPublication . McCleary, NJ; Harmsen, WS; Haakenstad, El; Cleary, JM; Meyerhardt, JA; Zalcberg, J; Adams, R; Grothey, A; Sobrero, AF; Van Cutsem, E; Goldberg, RM; Peeters, M; Tabernero, J; Seymour, M; Saltz, LB; Giantonio, BJ; Arnold, D; Rothenberg, ML; Koopman, M; Schmoll, HJ; Pitot, HC; Hoff, PM; Tebbutt, N; Masi, G; Souglakos, J; Bokemeyer, C; Heinemann, V; Yoshino, T; Chibaudel, B; deGramont, A; Shi, Q; Lichtman, SMBackground: We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials. Methods: Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first- and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum. All statistical tests were 2-sided. Results: Older adults comprised 16.4% of patients on first-line trials (870 total older adults aged >70 years; 4419 total younger adults aged ≤70 years, on first-line trials). Older adults and those with Eastern Cooperative Oncology Group Performance Status >0 were less likely to receive second-line therapy than younger adults. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariable analysis (odds ratio = 1.11, 95% confidence interval = 1.02 to 1.21, P = .01). Older and younger adults enrolled in second-line trials experienced similar median TTP and median OS (median TTP = 5.1 vs 5.2 months, respectively; median OS = 11.6 vs 12.4 months, respectively). Conclusions: Older adults were less likely to receive second-line therapy for metastatic colorectal cancer, though we did not observe a statistical difference in survival outcomes vs younger adults following second-line therapy. Further study should examine factors affecting decisions to treat older adults with second-line therapy. Inclusion of geriatric assessment may provide better criteria regarding the risks and benefits of second-line therapy.
- Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trialsPublication . Arnold, D; Lueza, B; Douillard, J-Y; Peeters, M; Lenz, H-J; Venook, A; Heinemann, V; Van Cutsem, E; Pignon, J-P; Tabernero, J; Cervantes, A; Ciardiello, FBACKGROUND: There is increasing evidence that metastatic colorectal cancer (mCRC) is a genetically heterogeneous disease and that tumours arising from different sides of the colon (left versus right) have different clinical outcomes. Furthermore, previous analyses comparing the activity of different classes of targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that primary tumour location (side), might be both prognostic and predictive for clinical outcome. METHODS: This retrospective analysis investigated the prognostic and predictive influence of the localization of the primary tumour in patients with unresectable RAS wt mCRC included in six randomized trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy plus EGFR antibody therapy (experimental arm) with chemotherapy or chemotherapy and bevacizumab (control arms). Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) for patients with left-sided versus right-sided tumours, and odds ratios (ORs) for objective response rate (ORR) were estimated by pooling individual study HRs/ORs. The predictive value was evaluated by pooling study interaction between treatment effect and tumour side. RESULTS: Primary tumour location and RAS mutation status were available for 2159 of the 5760 patients (37.5%) randomized across the 6 trials, 515 right-sided and 1644 left-sided. A significantly worse prognosis was observed for patients with right-sided tumours compared with those with left-sided tumours in both the pooled control and experimental arms for OS [HRs = 2.03 (95% CI: 1.69-2.42) and 1.38 (1.17-1.63), respectively], PFS [HRs = 1.59 (1.34-1.88) and 1.25 (1.06-1.47)], and ORR [ORs = 0.38 (0.28-0.50) and 0.56 (0.43-0.73)]. In terms of a predictive effect, a significant benefit for chemotherapy plus EGFR antibody therapy was observed in patients with left-sided tumours [HRs = 0.75 (0.67-0.84) and 0.78 (0.70-0.87) for OS and PFS, respectively] compared with no significant benefit for those with right-sided tumours [HRs = 1.12 (0.87-1.45) and 1.12 (0.87-1.44) for OS and PFS, respectively; P value for interaction <0.001 and 0.002, respectively]. For ORR, there was a trend (P value for interaction = 0.07) towards a greater benefit for chemotherapy plus EGFR antibody therapy in the patients with left-sided tumours [OR = 2.12 (1.77-2.55)] compared with those with right-sided tumours [OR = 1.47 (0.94-2.29)]. Exclusion of the unique phase II trial or the unique second-line trial had no impact on the results. The predictive effect on PFS may depend of the type of EGFR antibody therapy and on the presence or absence of bevacizumab in the control arm. CONCLUSION: This pooled analysis showed a worse prognosis for OS, PFS and ORR for patients with right-sided tumours compared with those with left-sided tumours in patients with RAS wt mCRC and a predictive effect of tumour side, with a greater effect of chemotherapy plus EGFR antibody therapy compared with chemotherapy or chemotherapy and bevacizumab, the effect being greatest in patients with left-sided tumours. These predictive results should be interpreted with caution due to the retrospective nature of the analysis, which was carried out on subpopulations of patients included in these trials, and because none of these studies contemplated a full treatment sequence strategy.
- Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancerPublication . Lutz, MP; Zalcberg, JR; Glynne-Jones, R; Ruers, T; Ducreux, M; Arnold, D; Aust, D; Brown, G; Bujko, K; Cunningham, C; Evrard, S; Folprecht, G; Gerard, JP; Habr-Gama, A; Haustermans, K; Holm, T; Kuhlmann, KF; Lordick, F; Mentha, G; Moehler, M; Nagtegaal, ID; Pigazzi, A; Puciarelli, S; Roth, A; Rutten, H; Schmoll, HJ; Sorbye, H; Van Cutsem, E; Weitz, J; Otto, FPrimary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.