Marc Buyse - Academia.edu (original) (raw)
Papers by Marc Buyse
Fluoropyrimidines in Cancer Therapy, 2002
Recherche en soins infirmiers, 2010
The Lancet Oncology, 2015
mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due t... more mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss, by sensitising PTEN-deficient tumours to trastuzumab. The BOLERO-1 study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer. In this phase 3, randomised, double-blind trial, patients were enrolled across 141 sites in 28 countries. Eligible patients were aged 18 years or older, with locally assessed HER2-positive advanced breast cancer, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, who had not received previous trastuzumab or chemotherapy for advanced breast cancer within 12 months of randomisation, had measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) or bone lesions in the absence of measurable disease, without previous systemic treatment for advanced disease except endocrine therapy. Patients were randomly assigned (2:1) with an interactive voice and web response system to receive either 10 mg everolimus once a day orally or placebo plus weekly trastuzumab intravenously at 4 mg/kg loading dose on day 1 with subsequent weekly doses of 2 mg/kg of each 4 week cycle plus paclitaxel intravenously at a dose of 80 mg/m(2) on days 1, 8, and 15 of each 4 week cycle. Randomisation was stratified according to previous use of trastuzumab and visceral metastasis. Patients and investigators were masked to the assigned treatments. Identity of experimental treatments was concealed by use of everolimus and placebo that were identical in packaging, labelling, appearance, and administration schedule. The two primary objectives were investigator-assessed progression-free survival in the full study population and in the subset of patients with hormone receptor-negative breast cancer at baseline; the latter was added during the course of the study, before unmasking based on new clinical and biological findings from other studies. All efficacy analyses were based on the intention-to-treat population. Enrolment for this trial is closed and results of the final progression-free survival analyses are presented here. This trial is registered with ClinicalTrials.gov, number NCT00876395. Between Sept 10, 2009, and Dec 16, 2012, 719 patients were randomly assigned to receive everolimus (n=480) or placebo (n=239). Median follow-up was 41·3 months (IQR 35·4-46·6). In the full population, median progression-free survival was 14·95 months (95% CI 14·55-17·91) with everolimus versus 14·49 months (12·29-17·08) with placebo (hazard ratio 0·89, 95% CI 0·73-1·08; p=0·1166). In the HR-negative subpopulation (n=311), median progression-free survival with everolimus was 20·27 months (95% CI 14·95-24·08) versus 13·08 months (10·05-16·56) with placebo (hazard ratio 0·66, 95% CI 0·48-0·91; p=0·0049); however, the protocol-specified significance threshold (p=0·0044) was not crossed. The most common adverse events with everolimus were stomatitis (314 [67%] of 472 patients in the everolimus group vs 77 [32%] of 238 patients in the placebo group), diarrhoea (267 [57%] vs 111 [47%] patients), and alopecia (221 [47%] vs 125 [53%]). The most frequently reported grade 3 or 4 adverse events in the everolimus group versus the placebo group were neutropenia (117 [25%] vs 35 [15%]), stomatitis (59 [13%] vs three [1%]), anaemia (46 [10%] vs six [3%]) and diarrhoea (43 [9%] vs 10 [4%]) On-treatment adverse event-related deaths were reported in 17 (4%) patients in the everolimus group and none in the placebo group. Although progression-free survival was not significantly different between groups in the full analysis population, the 7·2 months prolongation we noted with the addition of everolimus in the HR-negative, HER2-positive population warrants further investigation, even if it did not meet prespecified criteria for significance. The safety profile was generally consistent with what was previously reported in BOLERO-3. Proactive monitoring and early management of adverse events in patients given everolimus and chemotherapy is crucial. Novartis Pharmaceuticals.
Statistics for Biology and Health, 2014
European Journal of Cancer Supplements, 2009
Background: Motesanib (M) is an oral tyrosine kinase inhibitor of VEGF, PDGF and Kit receptors. W... more Background: Motesanib (M) is an oral tyrosine kinase inhibitor of VEGF, PDGF and Kit receptors. We assessed, in an ongoing double-blinded placebo-controlled trial, the effect of adding M to P as first line treatment of patients (pts) with MBC. A P plus bevacizumab (B) arm was included. The CIRG/TORI 010 study was supported by Amgen. Methods: 282 pts with HER2-negative and measurable MBC were randomly assigned treatment with P 90 mg/m 2 on days 1, 8 and 15 in combination with blinded placebo (P: arm A), blinded M 125 mg once daily (PM: arm B) or open label B 10 mg/kg on days 1 and 15 (PB: arm C). Treatment was administered in 28-day cycles until disease progression, toxicity or consent withdrawal. The primary objective was to determine the difference in response rate (RR) between P and PM. Treatment efficacy was assessed every 8 weeks according to RECIST and scans were independently centrally reviewed. Results: 277 pts received the assigned treatment. Pts characteristics at entry were balanced: median age was 55, 80% had hormone receptor positive tumors and 66% had received prior chemotherapy with curative intent. At the first planned analysis, 16 weeks after last patient enrolment, the median treatment duration was 6 cycles. The median cumulative dose of P was similar across the arms: 1328, 1282 and 1438 mg/m 2 in arm A, B and C, respectively. Pts received a median cumulative dose of B=133 mg/kg (arm C) and an averaged daily dose of M = 111 mg (arm B). The table displays the efficacy results and relevant differences in toxicities incidences (all grade).
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 1991
The aim of this multicentric prospective randomized clinical trial was to study the efficacy of h... more The aim of this multicentric prospective randomized clinical trial was to study the efficacy of hepatic artery ligation (HAL) with and without portal infusion (PI) of 5-FU in patients with liver metastasis of colorectal origin. Seventy-four patients were randomized. Sixty-seven were fully evaluable. Thirty-five patients were eligible in the HAL + PI of 5-FU group and 32 in the HAL alone group. The 5-FU infusion had to be discontinued for technical reasons in 13 patients. Complications of HAL were relatively high, including four hepatic failures (WHO grading greater than 2). Side effects of chemotherapy were limited. Five patients out of 30 had a partial response (WHO criteria) and one patient had a complete response in the group treated by HAL and PI of 5-FU. Only one patient had a partial response in the HAL alone group. Median survival for both groups was 12 months. Median time to progression for both groups was 6 months. This study did not show any advantage of delivery using the...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, Jan 19, 2015
Post-treatment survival experience of early colon cancer (CC) patients is well described in the l... more Post-treatment survival experience of early colon cancer (CC) patients is well described in the literature, which states that cure is probable for some patients. However, comparisons of treated patients' survival versus that expected from a matched general population (MGP) are limited. A total of 32 745 patients from 25 randomized adjuvant trials conducted from 1977 to 2012 in 41 countries were pooled. Observed long-term survival of these patients was compared with expected survival matched on sex, age, country, and year, both overall and by stage (II and III), sex, treatment [surgery, 5-fluorouracil (5-FU), 5-FU + oxaliplatin], age (<70 and 70+), enrollment year (pre/post 2000), and recurrence (yes/no). Comparisons were made at randomization and repeated conditional on survival to 1, 2, 3, and 5 years. CC and MGP equivalence was tested, and observed Kaplan-Meier survival rates compared with expected MGP rates 3 years out from each landmark. Analyses were also repeated in pat...
Bulletin du cancer, 2012
In castrate-refractory prostate cancers, main efficacy endpoints are progression free survival fo... more In castrate-refractory prostate cancers, main efficacy endpoints are progression free survival for phase-II trials and overall survival for phase-III trials. However, various progression criteria have been used, and overall survival may become more difficult to impact due to the recent approval of more effective drugs. PSA is useful in clinical practice, provided it is interpreted with caution, but cannot be used as a surrogate endpoint in clinical trials. Finally, circulating tumor cells represent a promising area of development.
Recherche en soins infirmiers, 2010
The authors mention the existing methods to perform meta-analysis, and show that meta-analysis ba... more The authors mention the existing methods to perform meta-analysis, and show that meta-analysis based on individual patient data (IPD meta-analyses) are the most reliable. Taking the example of 4 successive meta-analysis of clinical trials in advanced colorectal cancer, they illustrate the possibilities of IPD meta-analysis. They conclude that meta-analysis are a powerful tool not only to confirm small differences between treatment modalities, but also to generate hypothesis, to perform exploratory subgroup analysis, and to study potential surrogate endpoints.
Lancet, Jan 29, 2000
Treatment of advanced colorectal cancer has progressed substantially. However, improvements in re... more Treatment of advanced colorectal cancer has progressed substantially. However, improvements in response rates have not always translated into significant survival benefits. Doubts have therefore been raised about the usefulness of tumour response as a clinical endpoint. This meta-analysis was done on individual data from 3791 patients enrolled in 25 randomised trials of first-line treatment with standard bolus intravenous fluoropyrimidines versus experimental treatments (fluorouracil plus leucovorin, fluorouracil plus methotrexate, fluorouracil continuous infusion, or hepatic-arterial infusion of floxuridine). Analyses were by intention to treat. Compared with bolus fluoropyrimidines, experimental fluoropyrimidines led to significantly higher tumour response rates (454 responses among 2031 patients vs 209 among 1760; odds ratio 0.48 [95% CI 0.40-0.57], p<0.0001) and better survival (1808 deaths among 2031 vs 1580 among 1760; hazard ratio 0.90 [0.84-0.97], p=0.003). The survival b...
British journal of cancer, 1998
The purpose of this systematic study was to provide an up to date and reliable quantitative summa... more The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.
Fluoropyrimidines in Cancer Therapy, 2002
Recherche en soins infirmiers, 2010
The Lancet Oncology, 2015
mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due t... more mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss, by sensitising PTEN-deficient tumours to trastuzumab. The BOLERO-1 study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer. In this phase 3, randomised, double-blind trial, patients were enrolled across 141 sites in 28 countries. Eligible patients were aged 18 years or older, with locally assessed HER2-positive advanced breast cancer, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, who had not received previous trastuzumab or chemotherapy for advanced breast cancer within 12 months of randomisation, had measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) or bone lesions in the absence of measurable disease, without previous systemic treatment for advanced disease except endocrine therapy. Patients were randomly assigned (2:1) with an interactive voice and web response system to receive either 10 mg everolimus once a day orally or placebo plus weekly trastuzumab intravenously at 4 mg/kg loading dose on day 1 with subsequent weekly doses of 2 mg/kg of each 4 week cycle plus paclitaxel intravenously at a dose of 80 mg/m(2) on days 1, 8, and 15 of each 4 week cycle. Randomisation was stratified according to previous use of trastuzumab and visceral metastasis. Patients and investigators were masked to the assigned treatments. Identity of experimental treatments was concealed by use of everolimus and placebo that were identical in packaging, labelling, appearance, and administration schedule. The two primary objectives were investigator-assessed progression-free survival in the full study population and in the subset of patients with hormone receptor-negative breast cancer at baseline; the latter was added during the course of the study, before unmasking based on new clinical and biological findings from other studies. All efficacy analyses were based on the intention-to-treat population. Enrolment for this trial is closed and results of the final progression-free survival analyses are presented here. This trial is registered with ClinicalTrials.gov, number NCT00876395. Between Sept 10, 2009, and Dec 16, 2012, 719 patients were randomly assigned to receive everolimus (n=480) or placebo (n=239). Median follow-up was 41·3 months (IQR 35·4-46·6). In the full population, median progression-free survival was 14·95 months (95% CI 14·55-17·91) with everolimus versus 14·49 months (12·29-17·08) with placebo (hazard ratio 0·89, 95% CI 0·73-1·08; p=0·1166). In the HR-negative subpopulation (n=311), median progression-free survival with everolimus was 20·27 months (95% CI 14·95-24·08) versus 13·08 months (10·05-16·56) with placebo (hazard ratio 0·66, 95% CI 0·48-0·91; p=0·0049); however, the protocol-specified significance threshold (p=0·0044) was not crossed. The most common adverse events with everolimus were stomatitis (314 [67%] of 472 patients in the everolimus group vs 77 [32%] of 238 patients in the placebo group), diarrhoea (267 [57%] vs 111 [47%] patients), and alopecia (221 [47%] vs 125 [53%]). The most frequently reported grade 3 or 4 adverse events in the everolimus group versus the placebo group were neutropenia (117 [25%] vs 35 [15%]), stomatitis (59 [13%] vs three [1%]), anaemia (46 [10%] vs six [3%]) and diarrhoea (43 [9%] vs 10 [4%]) On-treatment adverse event-related deaths were reported in 17 (4%) patients in the everolimus group and none in the placebo group. Although progression-free survival was not significantly different between groups in the full analysis population, the 7·2 months prolongation we noted with the addition of everolimus in the HR-negative, HER2-positive population warrants further investigation, even if it did not meet prespecified criteria for significance. The safety profile was generally consistent with what was previously reported in BOLERO-3. Proactive monitoring and early management of adverse events in patients given everolimus and chemotherapy is crucial. Novartis Pharmaceuticals.
Statistics for Biology and Health, 2014
European Journal of Cancer Supplements, 2009
Background: Motesanib (M) is an oral tyrosine kinase inhibitor of VEGF, PDGF and Kit receptors. W... more Background: Motesanib (M) is an oral tyrosine kinase inhibitor of VEGF, PDGF and Kit receptors. We assessed, in an ongoing double-blinded placebo-controlled trial, the effect of adding M to P as first line treatment of patients (pts) with MBC. A P plus bevacizumab (B) arm was included. The CIRG/TORI 010 study was supported by Amgen. Methods: 282 pts with HER2-negative and measurable MBC were randomly assigned treatment with P 90 mg/m 2 on days 1, 8 and 15 in combination with blinded placebo (P: arm A), blinded M 125 mg once daily (PM: arm B) or open label B 10 mg/kg on days 1 and 15 (PB: arm C). Treatment was administered in 28-day cycles until disease progression, toxicity or consent withdrawal. The primary objective was to determine the difference in response rate (RR) between P and PM. Treatment efficacy was assessed every 8 weeks according to RECIST and scans were independently centrally reviewed. Results: 277 pts received the assigned treatment. Pts characteristics at entry were balanced: median age was 55, 80% had hormone receptor positive tumors and 66% had received prior chemotherapy with curative intent. At the first planned analysis, 16 weeks after last patient enrolment, the median treatment duration was 6 cycles. The median cumulative dose of P was similar across the arms: 1328, 1282 and 1438 mg/m 2 in arm A, B and C, respectively. Pts received a median cumulative dose of B=133 mg/kg (arm C) and an averaged daily dose of M = 111 mg (arm B). The table displays the efficacy results and relevant differences in toxicities incidences (all grade).
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 1991
The aim of this multicentric prospective randomized clinical trial was to study the efficacy of h... more The aim of this multicentric prospective randomized clinical trial was to study the efficacy of hepatic artery ligation (HAL) with and without portal infusion (PI) of 5-FU in patients with liver metastasis of colorectal origin. Seventy-four patients were randomized. Sixty-seven were fully evaluable. Thirty-five patients were eligible in the HAL + PI of 5-FU group and 32 in the HAL alone group. The 5-FU infusion had to be discontinued for technical reasons in 13 patients. Complications of HAL were relatively high, including four hepatic failures (WHO grading greater than 2). Side effects of chemotherapy were limited. Five patients out of 30 had a partial response (WHO criteria) and one patient had a complete response in the group treated by HAL and PI of 5-FU. Only one patient had a partial response in the HAL alone group. Median survival for both groups was 12 months. Median time to progression for both groups was 6 months. This study did not show any advantage of delivery using the...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, Jan 19, 2015
Post-treatment survival experience of early colon cancer (CC) patients is well described in the l... more Post-treatment survival experience of early colon cancer (CC) patients is well described in the literature, which states that cure is probable for some patients. However, comparisons of treated patients' survival versus that expected from a matched general population (MGP) are limited. A total of 32 745 patients from 25 randomized adjuvant trials conducted from 1977 to 2012 in 41 countries were pooled. Observed long-term survival of these patients was compared with expected survival matched on sex, age, country, and year, both overall and by stage (II and III), sex, treatment [surgery, 5-fluorouracil (5-FU), 5-FU + oxaliplatin], age (<70 and 70+), enrollment year (pre/post 2000), and recurrence (yes/no). Comparisons were made at randomization and repeated conditional on survival to 1, 2, 3, and 5 years. CC and MGP equivalence was tested, and observed Kaplan-Meier survival rates compared with expected MGP rates 3 years out from each landmark. Analyses were also repeated in pat...
Bulletin du cancer, 2012
In castrate-refractory prostate cancers, main efficacy endpoints are progression free survival fo... more In castrate-refractory prostate cancers, main efficacy endpoints are progression free survival for phase-II trials and overall survival for phase-III trials. However, various progression criteria have been used, and overall survival may become more difficult to impact due to the recent approval of more effective drugs. PSA is useful in clinical practice, provided it is interpreted with caution, but cannot be used as a surrogate endpoint in clinical trials. Finally, circulating tumor cells represent a promising area of development.
Recherche en soins infirmiers, 2010
The authors mention the existing methods to perform meta-analysis, and show that meta-analysis ba... more The authors mention the existing methods to perform meta-analysis, and show that meta-analysis based on individual patient data (IPD meta-analyses) are the most reliable. Taking the example of 4 successive meta-analysis of clinical trials in advanced colorectal cancer, they illustrate the possibilities of IPD meta-analysis. They conclude that meta-analysis are a powerful tool not only to confirm small differences between treatment modalities, but also to generate hypothesis, to perform exploratory subgroup analysis, and to study potential surrogate endpoints.
Lancet, Jan 29, 2000
Treatment of advanced colorectal cancer has progressed substantially. However, improvements in re... more Treatment of advanced colorectal cancer has progressed substantially. However, improvements in response rates have not always translated into significant survival benefits. Doubts have therefore been raised about the usefulness of tumour response as a clinical endpoint. This meta-analysis was done on individual data from 3791 patients enrolled in 25 randomised trials of first-line treatment with standard bolus intravenous fluoropyrimidines versus experimental treatments (fluorouracil plus leucovorin, fluorouracil plus methotrexate, fluorouracil continuous infusion, or hepatic-arterial infusion of floxuridine). Analyses were by intention to treat. Compared with bolus fluoropyrimidines, experimental fluoropyrimidines led to significantly higher tumour response rates (454 responses among 2031 patients vs 209 among 1760; odds ratio 0.48 [95% CI 0.40-0.57], p<0.0001) and better survival (1808 deaths among 2031 vs 1580 among 1760; hazard ratio 0.90 [0.84-0.97], p=0.003). The survival b...
British journal of cancer, 1998
The purpose of this systematic study was to provide an up to date and reliable quantitative summa... more The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.