Showing papers by "Laurence Collette published in 2019"
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Netherlands Cancer Institute1, Radboud University Nijmegen2, Princess Margaret Cancer Centre3, Cardiff University4, Institut Jules Bordet5, University of Amsterdam6, Maastricht University7, Université de Montréal8, University Medical Center Groningen9, Ghent University10, Cliniques Universitaires Saint-Luc11, European Organisation for Research and Treatment of Cancer12, Bristol-Myers Squibb13
TL;DR: This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib and may identify patients with inherent resistance to systemic therapy before planned CN.
Abstract: Importance In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown. Objective To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib. Design, Setting, and Participants This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied. Interventions Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy. Main Outcomes and Measures Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points. Results The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95;P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%). Conclusions and Relevance Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib. Trial Registration ClinicalTrials.gov identifier:NCT01099423
311 citations
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TL;DR: In this exploratory analysis of the international, multi-institutional randomized clinical trial EORTC 22952-26001, local control of brain metastases was similar between SRS and surgical resection groups, although the relative benefit decreased with time.
Abstract: Importance Brain metastases are a common source of morbidity for patients with cancer, and limited data exist to support the local therapeutic choice between surgical resection and stereotactic radiosurgery (SRS). Objective To evaluate local control of brain metastases among patients treated with SRS vs surgical resection within the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial. Design, Setting, and Participants This unplanned, exploratory analysis of the international, multi-institutional randomized clinical trial EORTC 22952-26001 (conducted from 1996-2007) was performed from February 9, 2017, through July 25, 2018. The EORTC 22952-26001 trial randomized patients with 1 to 3 brain metastases to whole-brain radiotherapy vs observation after complete surgical resection or before SRS. Patients in the present analysis were stratified but not randomized according to local modality (SRS or surgical resection) and treated per protocol with 1 to 2 brain metastases and tumors with a diameter of no greater than 4 cm. Interventions Surgical resection or SRS. Main Outcomes and Measures The primary end point was local recurrence of treated lesions. Cumulative incidence of local recurrence was calculated according to modality (surgical resection vs SRS) with competing risk regression to adjust for prognostic factors and competing risk of death. Results A total of 268 patients were included in the analysis (66.4% men; median age, 60.7 years [range, 26.9-81.1 years]); 154 (57.5%) underwent SRS and 114 (42.5%) underwent surgical resection. Median follow-up time was 39.9 months (range, 26.0-1982.0 months). Compared with the SRS group, patients undergoing surgical resection had larger metastases (median 28 mm [range, 10-40 mm] vs 20 mm [range, 4-40 mm];P Conclusions and Relevance In this exploratory analysis, local control of brain metastases was similar between SRS and surgical resection groups. Stereotactic radiosurgery was associated with improved early local control of treated lesions compared with surgical resection, although the relative benefit decreased with time. Trial Registration ClinicalTrials.gov Identifier:NCT00002899
77 citations
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TL;DR: This data indicates that conventional chemotherapy for metastatic castration resistant prostate cancer may cause skeletal fractures, which are a frequent and underestimated side-effect of systemic treatment, to be more widespread in women than in men.
Abstract: 5007Background: Skeletal fractures, pathological or not, are a frequent and underestimated side-effect of systemic treatment of metastatic castration resistant prostate cancer (mCRPC). The ERA223 t...
59 citations
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TL;DR: Reporting of surrogate endpoint evaluation using meta-analyses using ReSEEM guidelines and recommendations will improve the quality in reporting and facilitate the interpretation and reproducibility of meta-analytic surrogacy evaluation.
Abstract: Background Meta-analysis of randomized controlled trials (RCTs) has been widely conducted for the evaluation of surrogate endpoints in oncology, but little attention has been given to the adequacy of reporting and interpretation. This review evaluated the reporting quality of published meta-analyses on surrogacy evaluation and developed recommendations for future reporting. Methods We searched PubMed through August 2017 to identify studies that evaluated surrogate endpoints using the meta-analyses of RCTs in oncology. Both individual patient data (IPD) and aggregate data (AD) meta-analyses were included for the review. Results Eighty meta-analyses were identified: 22 used IPD and 58 used AD from multiple RCTs. We observed variability and reporting deficiencies in both IPD and AD meta-analyses, especially on reporting of trial selection, endpoint definition, study and patient characteristics for included RCTs, and important statistical methods and results. Based on these findings, we proposed a checklist and recommendations to improve completeness, consistency, and transparency of reports of meta-analytic surrogacy evaluation. We highlighted key aspects of the design and analysis of surrogate endpoints and presented explanations and rationale why these items should be clearly reported in surrogacy evaluation. Conclusions Our reporting of surrogate endpoint evaluation using meta-analyses (ReSEEM) guidelines and recommendations will improve the quality in reporting and facilitate the interpretation and reproducibility of meta-analytic surrogacy evaluation. Also, they should help promote greater methodological consistency and could also serve as an evaluation tool in the peer review process for assessing surrogacy research.
38 citations
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TL;DR: Findings show that these frameworks are not immediately transferable to locoregional cancer treatments, and calls for a new framework that includes real-world evidence with focus on the whole spectrum of patient-centred endpoints.
Abstract: Surgery and radiotherapy, two locoregional cancer treatments, are essential to help improve cancer outcomes, control, and palliation. The continued evolution in treatment processes, techniques, and technologies-often at substantially increased costs-demands for direction on outcomes that are most valued by patients, and the evidence that is required before clinical adoption of these practices. Three recently introduced frameworks-the European Society for Medical Oncology Magnitude of Clinical Benefit Scale, the American Society of Clinical Oncology Value Framework, and the National Comprehensive Cancer Network Blocks-which all help define the value of oncology treatments, were appraised with a focus on their methods and definition of patient benefit. In this Review, we investigate the applicability of these frameworks to surgical and radiotherapy innovations. Findings show that these frameworks are not immediately transferable to locoregional cancer treatments. Moreover, the lack of emphasis on patient perspective and the reliance on traditional, trial-based endpoints such as survival, disease-free survival, and safety, calls for a new framework that includes real-world evidence with focus on the whole spectrum of patient-centred endpoints. Such an evidence-informed value scale would safeguard against the proliferation of low-value innovation while simultaneously increasing access to treatments that show significant improvements in the outcomes of cancer care.
37 citations
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Netherlands Cancer Institute1, Radboud University Nijmegen2, Cardiff University3, Institut Jules Bordet4, Halifax5, Maastricht University6, Université de Montréal7, Queen Mary University of London8, University Medical Center Groningen9, Ghent University Hospital10, Cliniques Universitaires Saint-Luc11, European Organisation for Research and Treatment of Cancer12, University College London13
TL;DR: Patients with metastatic kidney cancer do not have more surgical complications irrespective of whether they are treated with systemic therapy before or after surgery, and surgical safety from a randomised comparison of CN before or before sunitinib is reported.
28 citations
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University of California, Los Angeles1, European Organisation for Research and Treatment of Cancer2, Cedars-Sinai Medical Center3, Centre Hospitalier Universitaire de Grenoble4, University of Paris5, University of Amsterdam6, Fox Chase Cancer Center7, Veterans Health Administration8, University of Michigan9
TL;DR: These data suggest that prolonged durations of ADT improve survival outcomes in both GG 4 disease and GG 5 disease, albeit with different optimal durations, as well as strategies to maintain the efficacy ofADT while minimizing its duration.
Abstract: Importance Androgen deprivation therapy (ADT) improves survival outcomes in patients with high-risk prostate cancer (PCa) treated with radiotherapy (RT). Whether this benefit differs between patients with Gleason grade group (GG) 4 (formerly Gleason score 8) and GG 5 (formerly Gleason score 9-10) disease remains unknown. Objective To determine whether the effectiveness of ADT duration varies between patients with GG 4 vs GG 5 PCa. Design, Setting, and Participants Traditional and network individual patient data meta-analyses of 992 patients (593 GG 4 and 399 GG 5) who were enrolled in 6 randomized clinical trials were carried out. Main Outcomes and Measures Multivariable Cox proportional hazard models were used to obtain hazard ratio (HR) estimates of ADT duration effects on overall survival (OS) and distant metastasis-free survival (DMFS). Cause-specific competing risk models were used to estimate HRs for cancer-specific survival (CSS). The interaction of ADT with GS was incorporated into the multivariable models. Traditional and network meta-analysis frameworks were used to compare outcomes of patients treated with RT alone, short-term ADT (STADT), long-term ADT (LTADT), and lifelong ADT. Results Five hundred ninety-three male patients (mean age, 70 years; range, 43-88 years) with GG 4 and 399 with GG 5 were identified. Median follow-up was 6.4 years. Among GG 4 patients, LTADT and STADT improved OS over RT alone (HR, 0.43; 95% CI, 0.26-0.70 and HR, 0.59; 95% CI, 0.38-0.93, respectively;P = .03 for both), whereas lifelong ADT did not (HR, 0.84; 95% CI, 0.54-1.30;P = .44). Among GG 5 patients, lifelong ADT improved OS (HR, 0.48; 95% CI, 0.31-0.76;P = .04), whereas neither LTADT nor STADT did (HR, 0.80; 95% CI, 0.45-1.44 and HR, 1.13; 95% CI, 0.69-1.87;P = .45 andP = .64, respectively). Among all patients, and among those receiving STADT, GG 5 patients had inferior OS compared with GG 4 patients (HR, 1.25; 95% CI, 1.07-1.47 and HR, 1.40; 95% CI, 1.05-1.88, respectively;P = .02). There was no significant OS difference between GG 5 and GG 4 patients receiving LTADT or lifelong ADT (HR, 1.21; 95% CI, 0.89-1.65 and HR, 0.85; 95% CI, 0.53-1.37;P = .23 andP = .52, respectively). Conclusions and Relevance These data suggest that prolonged durations of ADT improve survival outcomes in both GG 4 disease and GG 5 disease, albeit with different optimal durations. Strategies to maintain the efficacy of ADT while minimizing its duration (potentially with enhanced potency agents) should be investigated.
23 citations
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13 citations
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European Organisation for Research and Treatment of Cancer1, Copenhagen University Hospital2, Erasmus University Rotterdam3, Indiana University – Purdue University Indianapolis4, Institut Gustave Roussy5, Princess Margaret Cancer Centre6, Memorial Sloan Kettering Cancer Center7, Medical Research Council8, The Royal Marsden NHS Foundation Trust9, Harvard University10, University of Calgary11, University of Zurich12
TL;DR: PFS improved for poor risk patients, while OS improved in all IGCCCG risk groups, while a new prognostic model including older age and presence of lung metastases as additional negative factors is proposed.
13 citations
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University of Paris1, Katholieke Universiteit Leuven2, Northwood University3, American College of Radiology4, Leonard Davis Institute of Health Economics5, University of Texas MD Anderson Cancer Center6, Vanderbilt University Medical Center7, London Clinic8, European Organisation for Research and Treatment of Cancer9
TL;DR: For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome and further trials involving modern techniques may better define optimal OTT and total dose.
8 citations
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TL;DR: The cumulative incidence of toxicity at the MTD was higher than the usually accepted toxicity targets, challenging the definition of the RP2D of MTAs.
Abstract: Background In the era of molecularly targeted agents (MTAs), it is recommended to account for toxicity over several cycles to identify the recommended phase II dose (RP2D). We investigated the relationship between the risk of toxicity at cycle 1 and the cumulative incidence of toxicity over subsequent cycles in trials of single MTAs. Methods On individual patient data from 26 phase I clinical trials of single MTAs provided by the National Cancer Institute, we estimated the probability of first-severe toxicity per treatment cycle as well as the cumulative incidence at, below, and above the maximum tolerated dose (MTD). Toxicity was further subclassified into nonhematologic and hematologic. A prediction table was developed to estimate the cumulative incidence up to six cycles based on the toxicity rate observed in the first cycle. Results Overall, 942 patients were included. For patients treated at the MTD, the probability of first-severe toxicity decreased from 24.8% (95% prediction interval [PI] = 20.3% to 32.9%) to 2.2% (95% PI = 0.1% to 7.7%) from cycle 1 to 6, whereas the cumulative incidence of toxicity reached 51.7% (95% PI = 40.5% to 66.3%) after six cycles. Toxicity rates ranging from 20.0% to 30.0% in the first cycle were associated with 46.8% (95% PI = 39.5% to 54.2%) and 65.8% (95% PI = 57.7% to 73.1%) cumulative incidence after six cycles. Conclusion This study examined the risk of severe toxicity over time of single MTAs. The cumulative incidence of toxicity at the MTD was higher than the usually accepted toxicity targets, challenging the definition of the RP2D of MTAs. The prediction table may help calibrate the target rate at the RP2D.
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TL;DR: It is aimed to describe the differences and similarities between the two groups and to identify key factors for collaboration from the perspective of the young investigators of the networks.
Abstract: International/intercontinental collaboration is necessary to set up new innovative clinical trials for cancer treatment. However, the infrastructure, especially Asia-Europe academic partnerships, to enable such collaboration has not been fully structured and differences and similarities between the research groups have not been well studied. In 2015, collaboration started between the biggest cancer research organizations in Asia and EU, Japan Clinical Oncology Group (JCOG) and European Organisation for Research and Treatment of Cancer (EORTC). Following the first pilot collaboration study, the first scientific symposium took place in December 2017 in Tokyo. Before the symposium, a working visit for EORTC investigators from the Early Career Investigator initiative (ECI), willing to develop projects within the JCOG-EORTC partnership, was held. In addition to the digest of the working visit and symposium, we aimed to describe the differences and similarities between the two groups and to identify key factors for collaboration from the perspective of the young investigators of the networks. These findings are described in this article.