Author
C. Robert
Other affiliations: Université Paris-Saclay, University of Paris-Sud
Bio: C. Robert is an academic researcher from Institut Gustave Roussy. The author has contributed to research in topics: Melanoma & Ipilimumab. The author has an hindex of 24, co-authored 133 publications receiving 2100 citations. Previous affiliations of C. Robert include Université Paris-Saclay & University of Paris-Sud.
Topics: Melanoma, Ipilimumab, Vemurafenib, Pembrolizumab, Sorafenib
Papers published on a yearly basis
Papers
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312 citations
TL;DR: The results of this study suggest that personalised dosimetry is to improve outcomes in future trials of selective internal radiation therapy with yttrium-90-loaded glass microspheres and should be used in practice.
228 citations
Memorial Sloan Kettering Cancer Center1, Institut Gustave Roussy2, The Royal Marsden NHS Foundation Trust3, Netherlands Cancer Institute4, University of California, Los Angeles5, University Health Network6, University of Manchester7, University of Zurich8, Northwestern University9, Harvard University10, Genentech11, Peter MacCallum Cancer Centre12, University of Melbourne13
TL;DR: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up, and OS curves converged after ≈3 years, likely as a result of crossover from dacarbazine to vemurafen ib and receipt of subsequent anticancer therapies.
164 citations
TL;DR: The efficacy and safety of AZD6244 vs TMZ in an overall population of advanced melanoma pts and in mutated BRAF (BRAF+) or mutated NRAS (NRAS+) subgroups is evaluated and mutation status was assessed by DNA sequencing.
Abstract: 9033 Background: AZD6244 is an orally available, potent, selective, ATP uncompetitive inhibitor of MEK1/2, with preclinical and phase I data suggesting it has the potential for anti-tumor activity in pts with melanoma. Here we evaluate the efficacy and safety of AZD6244 vs TMZ in an overall population of advanced melanoma pts and in mutated BRAF (BRAF+) or mutated NRAS (NRAS+) subgroups. Methods: Eligibility included AJCC stage 3/4 malignant melanoma, RECIST measurable disease, and no prior chemotherapy for advanced melanoma. Pts were randomized 1:1 to AZD6244 (100mg BD continuously) or TMZ (200 mg/m2 for 5 days, q28d). Pts randomized to TMZ could receive AZD6244 after disease progression. The primary outcome variable was progression-free survival (PFS), which was then adjusted for source of primary tumor (uveal vs non-uveal), mutation status, LDH (> or ≤2 x ULN), and WHO PS (0–2). Mutation status was assessed in archival or fresh tumor samples by DNA sequencing. Results: A total of 104 and 96 pts were ra...
127 citations
St. Vincent's Health System1, Princess Margaret Cancer Centre2, University of Pennsylvania3, Mayo Clinic4, University of Texas at Austin5, University of Pittsburgh6, University of Sydney7, Merck & Co.8, Dana Corporation9, Institut Gustave Roussy10, University of California, Los Angeles11, Los Angeles Biomedical Research Institute12, University of California, Santa Barbara13, Memorial Sloan Kettering Cancer Center14, Moffitt Cancer Center15
TL;DR: 3-year OS data is presented for all patients with melanoma enrolled in the phase 1b KEYNOTE-001 study and the anti–PD-1 antibody pembro demonstrated superior PFS over chemotherapy for ipilimumab (ipi)-refractory melanoma.
Abstract: 9503Background: The anti–PD-1 antibody pembro (pembro; MK-3475) prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, and is approved for treating advanced melanoma at a dose of 2 mg/kg every 3 wk (Q3W). Pembro demonstrated superior PFS over chemotherapy for ipilimumab (ipi)-refractory melanoma (KEYNOTE-002) and superior OS and PFS over ipi for advanced melanoma (KEYNOTE-006). We present 3-year OS data for all patients (pts) with melanoma enrolled in the phase 1b KEYNOTE-001 study (NCT01295827). Methods: Pts were enrolled in ipi-naive and ipi-treated cohorts and received pembro 2 or 10 mg/kg Q3W or 10 mg/kg Q2W until intolerable toxicity, progression, or investigator decision. Clinically stable pts with radiographic progression could remain on pembro until progression was confirmed. Response was assessed by RECIST v1.1 every 12 wk. After pembro discontinuation, pts were contacted to assess survival every 3 mo. OS was estimated using the Kaplan-Meier method. Results: Of the 655 pts enrolled, 24% had ...
120 citations
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Memorial Sloan Kettering Cancer Center1, University of Kiel2, Institut Gustave Roussy3, Netherlands Cancer Institute4, The Royal Marsden NHS Foundation Trust5, University of Zurich6, University of Tübingen7, University of Manchester8, University of Paris9, University of Duisburg-Essen10, University of California, Los Angeles11, Vanderbilt University12, University of Pittsburgh13, University of Nantes14, Plexxikon15, Hoffmann-La Roche16, Genentech17, Harvard University18, Peter MacCallum Cancer Centre19
TL;DR: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation in a phase 3 randomized clinical trial.
Abstract: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Conclusions Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann–La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.)
6,773 citations
TL;DR: Calcium, CRP, C-reactive protein, CT, computed tomography, ESR, sedimentation rate, and checkpoint are used to estimate the concentration of phosphorous in the sediments.
1,821 citations
TL;DR: Because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation.
Abstract: Tumours with mutant BRAF are dependent on the RAF-MEK-ERK signalling pathway for their growth. We found that ATP-competitive RAF inhibitors inhibit ERK signalling in cells with mutant BRAF, but unexpectedly enhance signalling in cells with wild-type BRAF. Here we demonstrate the mechanistic basis for these findings. We used chemical genetic methods to show that drug-mediated transactivation of RAF dimers is responsible for paradoxical activation of the enzyme by inhibitors. Induction of ERK signalling requires direct binding of the drug to the ATP-binding site of one kinase of the dimer and is dependent on RAS activity. Drug binding to one member of RAF homodimers (CRAF-CRAF) or heterodimers (CRAF-BRAF) inhibits one protomer, but results in transactivation of the drug-free protomer. In BRAF(V600E) tumours, RAS is not activated, thus transactivation is minimal and ERK signalling is inhibited in cells exposed to RAF inhibitors. These results indicate that RAF inhibitors will be effective in tumours in which BRAF is mutated. Furthermore, because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation. These predictions have been borne out in a recent clinical trial of the RAF inhibitor PLX4032 (refs 4, 5). The model indicates that promotion of RAF dimerization by elevation of wild-type RAF expression or RAS activity could lead to drug resistance in mutant BRAF tumours. In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS.
1,599 citations
Erasmus University Rotterdam1, Peter MacCallum Cancer Centre2, Institut Gustave Roussy3, Charité4, French Institute of Health and Medical Research5, Katholieke Universiteit Leuven6, Leiden University7, European Organisation for Research and Treatment of Cancer8, The Royal Marsden NHS Foundation Trust9
TL;DR: If response induction is the only aim of treatment, a daily dose of400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.
1,525 citations
TL;DR: This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting.
Abstract: Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed.
1,269 citations