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Dive into the research topics where Derek J. Jonker is active.

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Featured researches published by Derek J. Jonker.


The New England Journal of Medicine | 2008

K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer

Christos Stelios Karapetis; Shirin Khambata-Ford; Derek J. Jonker; Dongsheng Tu; Niall C. Tebbutt; R. John Simes; Haji Chalchal; Jeremy David Shapiro; Sonia Robitaille; Timothy Jay Price; Lois Shepherd; Christiane Langer; Malcolm J. Moore; John Zalcberg

BACKGROUND Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value. METHODS We analyzed tumor samples, obtained from 394 of 572 patients (68.9%) with colorectal cancer who were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone, to look for activating mutations in exon 2 of the K-ras gene. We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups. RESULTS Of the tumors evaluated for K-ras mutations, 42.3% had at least one mutation in exon 2 of the gene. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival, respectively). In patients with wild-type K-ras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001) and progression-free survival (median, 3.7 months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 to 0.54; P<0.001). Among patients with mutated K-ras tumors, there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival (hazard ratio, 0.98; P=0.89) or progression-free survival (hazard ratio, 0.99; P=0.96). In the group of patients receiving best supportive care alone, the mutation status of the K-ras gene was not significantly associated with overall survival (hazard ratio for death, 1.01; P=0.97). CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab. The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone. (ClinicalTrials.gov number, NCT00079066.)


JAMA | 2010

Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab

Wendy De Roock; Derek J. Jonker; Federica Di Nicolantonio; Andrea Sartore-Bianchi; Dongsheng Tu; Salvatore Siena; Simona Lamba; Sabrina Arena; Milo Frattini; Hubert Piessevaux; Eric Van Cutsem; Christopher J. O'Callaghan; Shirin Khambata-Ford; John Zalcberg; John Simes; Christos Stelios Karapetis; Alberto Bardelli; Sabine Tejpar

CONTEXT Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. OBJECTIVE To test the hypothesis that KRAS codon 13 mutations are associated with a better outcome after treatment with cetuximab than observed with other KRAS mutations. DESIGN, SETTING, AND PATIENTS We studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008. Patients were included in the CO.17, BOND, MABEL, EMR202600, EVEREST, BABEL, or SALVAGE clinical trials or received off-study treatment. Univariate and multivariate analyses, adjusting for possible prognostic factors and data set, were performed. The effect of the different mutations was studied in vitro by constructing isogenic cell lines with wild-type KRAS, p.G12V, or p.G13D mutant alleles and treating them with cetuximab. MAIN OUTCOME MEASURES The main efficacy end point was overall survival. Secondary efficacy end points were response rate and progression-free survival. RESULTS In comparison with patients with other KRAS-mutated tumors, patients with p.G13D-mutated tumors (n = 32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7-20.5] months vs 5.7 [95% CI, 4.9-6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31-0.81; P = .005) and longer progression-free survival (median, 4.0 [95% CI, 1.9-6.2] months vs 1.9 [95% CI, 1.8-2.8] months; adjusted HR, 0.51; 95% CI, 0.32-0.81; P = .004). There was a significant interaction between KRAS mutation status (p.G13D vs other KRAS mutations) and overall survival benefit with cetuximab treatment (adjusted HR, 0.30; 95% CI, 0.14-0.67; P = .003). In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells. CONCLUSIONS In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutated tumors. Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted.


Nature | 2011

Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans

Caroline J. Breitbach; James Burke; Derek J. Jonker; Joe Stephenson; Andrew R. Haas; Laura Quan Man Chow; Jorge Nieva; Tae Ho Hwang; Anne Moon; Richard H. Patt; Adina Pelusio; Fabrice Le Boeuf; Joseph K. Burns; Laura Evgin; Naomi De Silva; Sara Cvancic; Terri Robertson; Ji Eun Je; Yeon Sook Lee; Kelley Parato; Jean-Simon Diallo; Aaron Fenster; Manijeh Daneshmand; John C. Bell; David Kirn

The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.


Lancet Oncology | 2013

Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial.

David Cunningham; István Láng; Eugenio Marcuello; Vito Lorusso; Janja Ocvirk; Dong Bok Shin; Derek J. Jonker; Stuart Osborne; Niko Andre; Daniel Waterkamp; Mark P Saunders

BACKGROUND Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer. METHODS For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m(2) orally twice a day on days 1-14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939. FINDINGS From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3-11·4] vs 5·1 months [4·2-6·3]; hazard ratio 0·53 [0·41-0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]). INTERPRETATION The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. FUNDING F Hoffmann-La Roche.


Journal of the National Cancer Institute | 2009

Prospective Cost-Effectiveness Analysis of Cetuximab in Metastatic Colorectal Cancer: Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial

Nicole Mittmann; Heather-Jane Au; Dongsheng Tu; Christopher J. O'Callaghan; Pierre K. Isogai; Christos Stelios Karapetis; John Zalcberg; William K. Evans; Malcolm J. Moore; Jehan Siddiqui; Brian Findlay; Bruce Colwell; John Simes; Peter Gibbs; Matthew Links; Niall C. Tebbutt; Derek J. Jonker

BACKGROUND The National Cancer Institute of Canada Clinical Trials Group CO.17 study showed that patients with advanced colorectal cancer had improved overall survival when cetuximab, an epidermal growth factor receptor-targeting antibody, was given in addition to best supportive care. We conducted a cost-effectiveness analysis using prospectively collected resource utilization and health utility data for patients in the CO.17 study who received cetuximab plus best supportive care (N = 283) or best supportive care alone (N = 274). METHODS Direct medical resource utilization data were collected, including medications, physician visits, toxicity management, blood products, emergency department visits, and hospitalizations. Mean survival times for the study arms were calculated for the entire population and for the subset of patients with wild-type KRAS tumors over an 18- to 19-month period. All costs were presented in 2007 Canadian dollars. One-way and probabilistic sensitivity analysis was used to determine the robustness of the results. Cost-effectiveness acceptability curves were determined. The 95% confidence intervals (CIs) for the incremental cost-effectiveness ratios and the incremental cost-utility ratios were estimated by use of a nonparametric bootstrapping method (with 1000 iterations). RESULTS For the entire study population, the mean improvement in overall and quality-adjusted survival with cetuximab was 0.12 years and 0.08 quality-adjusted life-years (QALYs), respectively. The incremental cost with cetuximab compared with best supportive care was


Journal of Clinical Oncology | 2013

Fluorouracil, Leucovorin, and Irinotecan Plus Either Sunitinib or Placebo in Metastatic Colorectal Cancer: A Randomized, Phase III Trial

Alfredo Carrato; Anna Swieboda-Sadlej; Marzanna Staszewska-Skurczynska; Robert C. Lim; Laslo Roman; Yaroslav Shparyk; Igor Bondarenko; Derek J. Jonker; Yan Sun; Jhony De La Cruz; J. Andrew Williams; Beata Korytowsky; James G. Christensen; Xun Lin; Jennifer M. Tursi; Maria Jose Lechuga; Eric Van Cutsem

23,969. The incremental cost-effectiveness ratio was


British Journal of Cancer | 2000

Survival benefit of chemotherapy in metastatic colorectal cancer: a meta-analysis of randomized controlled trials

Derek J. Jonker; Jean A. Maroun; W Kocha

199,742 per life-year gained (95% CI =


European Journal of Cancer | 2015

Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17

S.Y. Brulé; Derek J. Jonker; Christos Stelios Karapetis; Chris O’Callaghan; Malcolm J. Moore; Ralph Wong; Niall C. Tebbutt; Cr. Underhill; Desmond Yip; John Zalcberg; Dongsheng Tu; Rachel Anne Goodwin

125,973 to


Journal of Clinical Oncology | 2009

Health-Related Quality of Life in Patients With Advanced Colorectal Cancer Treated With Cetuximab: Overall and KRAS-Specific Results of the NCIC CTG and AGITG CO.17 Trial

Heather-Jane Au; Christos Stelios Karapetis; Christopher J. O'Callaghan; Dongsheng Tu; Malcolm J. Moore; John Zalcberg; Hagen F. Kennecke; Jeremy David Shapiro; Sheryl Koski; Nick Pavlakis; Danielle Charpentier; David Wyld; Michael Jefford; Gregory J. Knight; Nadine M Magoski; Michael Brundage; Derek J. Jonker

652,492 per life-year gained) and the incremental cost-utility ratio was


Clinical Cancer Research | 2014

PIK3CA, BRAF and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer - results from NCIC CTG / AGITG CO.17

Christos Stelios Karapetis; Derek J. Jonker; Manijeh Daneshmand; Jennifer Hanson; Christopher J. O'Callaghan; Celia Marginean; John Zalcberg; John Simes; Malcolm J. Moore; Niall C. Tebbutt; Timothy Jay Price; Jeremy David Shapiro; Nick Pavlakis; Peter Gibbs; Guy van Hazel; Ursula Lee; Rashida Haq; Shakeel Virk; Dongsheng Tu; Ian Lorimer

299,613 per QALY gained (95% CI =

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Malcolm J. Moore

Princess Margaret Cancer Centre

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Lillian L. Siu

Princess Margaret Cancer Centre

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