Publications by authors named "Jean-Philippe Metges"

41 Publications

Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors.

Sci Rep 2021 Mar 1;11(1):4727. Epub 2021 Mar 1.

EA GETBO 3878, University Hospital of Brest, Brest, France.

To present the feasibility of a dynamic whole-body (DWB) Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1-5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB Ga-DOTATOC-PET/CT acquisition in WD-NETs.
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http://dx.doi.org/10.1038/s41598-021-83965-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921579PMC
March 2021

Regorafenib-Avelumab Combination in Patients with Microsatellite Stable Colorectal Cancer (REGOMUNE): A Single-arm, Open-label, Phase II Trial.

Clin Cancer Res 2021 Jan 25. Epub 2021 Jan 25.

Early Phase Trials Unit, Institut Bergonié, Bordeaux, France.

Purpose: Regorafenib is synergistic with immune checkpoint inhibition in colorectal cancer preclinical models.

Patients And Methods: This was a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks on/1 week off, 160 mg every day; avelumab 10 mg/kg i.v. was given every 2 weeks, beginning at cycle 1, day 15 until progression or unacceptable toxicity. The primary endpoint was the confirmed objective response rate under treatment, as per RECIST 1.1. The secondary endpoints included a 1-year nonprogression rate, progression-free survival (PFS), and overall survival (OS), safety and biomarkers studies performed on sequential tumor samples obtained at baseline and at cycle 2 day 1.

Results: Forty-eight patients were enrolled in four centers. Forty-three were assessable for efficacy after central radiological review. Best response was stable disease for 23 patients (53.5%) and progressive disease for 17 patients (39.5%). The median PFS and OS were 3.6 months [95% confidence interval (CI), 1.8-5.4] and 10.8 months (95% CI, 5.9-NA), respectively. The most common grade 3 or 4 adverse events were palmar-plantar erythrodysesthesia syndrome ( = 14, 30%), hypertension ( = 11, 23%), and diarrhea ( = 6, 13%). High baseline infiltration by tumor-associated macrophages was significantly associated with adverse PFS (1.8 vs. 3.7 months; = 0.002) and OS (3.7 months vs. not reached; = 0.002). Increased tumor infiltration by CD8 T cells at cycle 2, day 1 as compared with baseline was significantly associated with better outcome.

Conclusions: The combination of regorafenib + avelumab mobilizes antitumor immunity in a subset of patients with microsatellite stable colorectal cancer. Computational pathology through quantification of immune cell infiltration may improve patient selection for further studies investigating this approach.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3416DOI Listing
January 2021

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial.

Eur J Cancer 2021 Jan 3;143:55-63. Epub 2020 Dec 3.

GERCOR, Paris, France; Department of Medical Oncology, Institut Curie - Site Saint Cloud, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France. Electronic address:

Background: The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in.

Methods: Patients received durvalumab (1500 mg at day 1 [D1] of each cycle)/tremelimumab (75 mg at D1 for 4 cycles; Arm A) or durvalumab/tremelimumab with paclitaxel (80 mg/m at D1, D8, D15; Arm B) every 28 days.

Results: Twenty patients were enrolled (Arm A/B: 10/10). There were no dose-limiting toxicities (DLTs) in Arm A. Six DLTs were observed in five patients (50%) in Arm B, meeting a stopping rule for the trial inclusions. DLTs included three serious anaphylactic reactions (with one cardiac arrest), two enterocolitis, and one infectious pneumopathy with septic shock. There were no patients with history of personal or familial auto-immune disease.

Conclusion: The safety run-in part of IMMUNOBIL PRODIGE 57 raised concerns regarding co-administration of paclitaxel with durvalumab and tremelimumab in BTC, with an unexpected increase in anaphylactic adverse events. Phase II of the study will only evaluate the durvalumab and tremelimumab combination arm.

Clinicaltrials Registration: NCT03704480.
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http://dx.doi.org/10.1016/j.ejca.2020.10.027DOI Listing
January 2021

Clinical Assessment of 177Lu-DOTATATE Quantification by Comparison of SUV-Based Parameters Measured on Both Post-PRRT SPECT/CT and 68Ga-DOTATOC PET/CT in Patients With Neuroendocrine Tumors: A Feasibility Study.

Clin Nucl Med 2021 Feb;46(2):111-118

Department of Oncology, University Hospital of Brest, Brest, France.

Patients And Methods: Patients with WD-GEP-NET who benefited from a pretherapeutic 68Ga-DOTATOC PET/CT and a 177Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1-10/patient; SUVmax, SUVmean, SUVpeak, MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUVmax and SUVmean (TLRmax, TLRmean, TSRmax, and TSRmean, respectively).

Results: Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV (P < 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR (P < 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779-0.845), weak for TLR parameters (0.365-0.394), and moderate-to-strong for TSR parameters (0.676-0.750).

Conclusions: Our results suggest the feasibility of 177Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68Ga-DOTATOC PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000003412DOI Listing
February 2021

Efficacy and safety of panitumumab in a cohort of patients with metastatic colorectal cancer in France: PANI OUEST, a post-EMA-approval descriptive study with a geriatric oncology focus.

Turk J Gastroenterol 2020 Oct;31(10):695-705

Observatory of Cancer BPL, Angers, France;West Institut of Cancer (ICO), Paul Papin, Angers, France.

Background/aims: The Bretagne-Pays de la Loire cancer observatory, an oncology network created by the French Ministry of Health, is specifically dedicated to assess the use of new targeted anticancer therapies in routine practice. In line with the French National Cancer III program, our cancer network set up a real-life cohort, which is independent of the pharmaceutical industry, for patients with colorectal cancer to monitor patient safety and quality of care and promote pharmacovigilance.

Materials And Methods: Panitumumab monotherapy was assessed in 243 patients with wild-type Kirsten rat sarcoma who were treated for metastatic colorectal cancer (mCRC) between July 2008 and December 2010 after prior chemotherapy using oxaliplatine and irinotecan. This was a post-European medicine agency marketing (EMA-M) study Results: This study shed light on the best practices, strategic adaptations, clinical results (treatment objective responses, 13%; progression free survival, 2.99 months [2.73-3.15]; and overall survival, 6.8 months [5.49-8.38]) as well as expected or unexpected (grade 3 or 4: 11.5%) secondary effects in the phase IV panitumumab treatment of mCRC.

Conclusion: Our results are similar to those by Amado whose phase III study led to obtaining EMA-M for panitumumab and tend to confirm the antitumor activity of this antiepidermal growth factor receptor antibody in the treatment of mCRC. In addition, our results opened avenues to further assessment of panitumumab use as monotherapy as well as its benefit-risk ratio while taking into account the patients' general and clinical characteristics. In 2012, the French National Authority for Health appended these data to the panitumumab transparency committee report.
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http://dx.doi.org/10.5152/tjg.2020.19219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659902PMC
October 2020

Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer.

J Clin Oncol 2020 Dec 7;38(35):4138-4148. Epub 2020 Oct 7.

CHU Brest - Institut de Cancerologie et d'Hematologie, Arpego Network, Brest, France.

Purpose: Patients with advanced esophageal cancer have a poor prognosis and limited treatment options after first-line chemotherapy.

Patients And Methods: In this open-label, phase III study, we randomly assigned (1:1) 628 patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab 200 mg every 3 weeks for up to 2 years or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). Primary end points were overall survival (OS) in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10, in patients with squamous cell carcinoma, and in all patients (one-sided α 0.9%, 0.8%, and 0.8%, respectively).

Results: At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3 6.7 months; hazard ratio [HR], 0.69 [95% CI, 0.52 to 0.93]; = .0074). Estimated 12-month OS rate was 43% (95% CI, 33.5% to 52.1%) with pembrolizumab versus 20% (95% CI, 13.5% to 28.3%) with chemotherapy. Median OS was 8.2 months versus 7.1 months (HR, 0.78 [95% CI, 0.63 to 0.96]; = .0095) in patients with squamous cell carcinoma and 7.1 months versus 7.1 months (HR, 0.89 [95% CI, 0.75 to 1.05]; = .0560) in all patients. Grade 3-5 treatment-related adverse events occurred in 18.2% of patients with pembrolizumab versus 40.9% in those who underwent chemotherapy.

Conclusion: Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10, with fewer treatment-related adverse events.
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http://dx.doi.org/10.1200/JCO.20.01888DOI Listing
December 2020

Three-Dimensional Culture Systems in Gastric Cancer Research.

Cancers (Basel) 2020 Sep 29;12(10). Epub 2020 Sep 29.

Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France.

Gastric cancer (GC), which includes cancer of the esophagus, the oesophagogastric junction, and the stomach fundus, is highly deadly with strong regional influence, Asia being the most affected. GC is often detected at late stages, with 30% of metastatic cases at diagnosis. Many authors have devised models to both unravel the mechanisms of GC development and to evaluate candidate therapeutics. Among these models, 2D-cell cultures are progressively replaced by 3D-cell cultures that recapitulate, much more comprehensively, tumor cellular and genetic heterogeneity, as well as responsiveness to environmental changes, such as exposure to drugs or irradiation. With respect to the specifics of GC, there are high hopes from such model systems, especially with the aim of identifying prognostic markers and novel drug targets.
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http://dx.doi.org/10.3390/cancers12102800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601358PMC
September 2020

Comparison of 4 Screening Methods for Detecting Fluoropyrimidine Toxicity Risk: Identification of the Most Effective, Cost-Efficient Method to Save Lives.

Dose Response 2020 Jul-Sep;18(3):1559325820951367. Epub 2020 Sep 14.

Institut de Cancérologie de l'Ouest, Angers, France.

Background: Fluoropyrimidines (FPs) carry around 20% risk of G3-5 toxicity and 0.2-1% risk of death, due to dihydropyrimidine dehydrogenase (DPD) deficiency. Several screening approaches exist for predicting toxicity, however there is ongoing debate over which method is best. This study compares 4 screening approaches.

Method: 472 patients treated for colorectal, head-and-neck, breast, or pancreatic cancers, who had not been tested pre-treatment for FP toxicity risk, were screened using: genotyping (G); phenotyping via plasma Uracil (U); phenotyping via plasma-dihydrouracil/uracil ratio (UH/U); and a Multi-Parametric Method (MPM) using genotype, phenotype, and epigenetic data. Performance was compared, particularly the inability to detect at-risk patients (false negatives).

Results: False negative rates for detecting G5 toxicity risk were 51.2%, 19.5%, 9.8% and 2.4%, for G, U, UH/U and MPM, respectively. False negative rates for detecting G4-5 toxicity risk were 59.8%, 36.1%, 21.3% and 4.7%, respectively. MPM demonstrated significantly (p < 0.001) better prediction performance.

Conclusion: MPM is the most effective method for limiting G4-5 toxicity. Its systematic implementation is cost-effective and significantly improves the risk-benefit ratio of FP-treatment. The use of MPM, rather than G or U testing, would avoid nearly 8,000 FP-related deaths per year globally (500 in France), and spare hundreds of thousands from G4 toxicity.
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http://dx.doi.org/10.1177/1559325820951367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493257PMC
September 2020

Diagnostic performance of a whole-body dynamic 68GA-DOTATOC PET/CT acquisition to differentiate physiological uptake of pancreatic uncinate process from pancreatic neuroendocrine tumor.

Medicine (Baltimore) 2020 Aug;99(33):e20021

EA GETBO 3878.

To evaluate the diagnostic performance of net influx rate (Ki) values from a whole-body dynamic (WBD) Ga-DOTATOC-PET/CT acquisition to differentiate pancreatic neuroendocrine tumors (pNETs) from physiological uptake of pancreatic uncinate process (UP).Patients who were benefited from a WBD acquisition for the assessment of a known well-differentiated neuroendocrine tumor (NET)/suspicion of disease in the prospective GAPET-NET cohort were screened. Only patients with a confirmed pNET/UP as our gold standard were included. The positron emission tomography (PET) procedure consisted in a single-bed dynamic acquisition centered on the heart, followed by a whole-body dynamic acquisition and then a static acquisition. Dynamic (Ki calculated according to Patlak method), static (SUVmax, SUVmean, SUVpeak) parameters, and tumor-to-liver and tumor-to-spleen ratio (TLRKi and TSRKi (according to hepatic/splenic Ki)), tumor SUVmax to liver SUVmax (TM/LM), tumor SUVmax to liver SUVmean (TM/Lm), tumor SUVmax to spleen SUVmax (TM/SM), and tumor SUVmax to spleen SUVmean (TM/Sm) (according to hepatic/splenic SUVmax and SUVmean respectively) were calculated. A Receiver Operating Characteristic (ROC) analysis was performed to evaluate their diagnostic performance to distinguish UP from pNET.One hundred five patients benefited from a WBD between July 2018 and July 2019. Eighteen (17.1%) had an UP and 26 (24.8%) a pNET. For parameters alone, the Ki and SUVpeak had the best sensitivity (88.5%) while the Ki, SUVmax, and SUVmean had the best specificity (94.4%). The best diagnostic accuracy was obtained with Ki (90.9%). For ratios, the TLRKi and the TSRKi had the best sensitivity (95.7%) while the TM/SM and TM/Sm the best specificity (100%). TLRKi had the best diagnostic accuracy (95.1%) and the best area under the curve (AUC) (0.990).Our study is the first one to evaluate the interest of a WBD acquisition to differentiate UP from pNETs and shows excellent diagnostic performances of the Ki approach.
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http://dx.doi.org/10.1097/MD.0000000000020021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437793PMC
August 2020

Sorafenib Plus Irinotecan Combination in Patients With RAS-mutated Metastatic Colorectal Cancer Refractory To Standard Combined Chemotherapies: A Multicenter, Randomized Phase 2 Trial (NEXIRI-2/PRODIGE 27).

Clin Colorectal Cancer 2020 Dec 15;19(4):301-310.e1. Epub 2020 May 15.

Medical Oncology Departement, Institut du Cancer de Montpellier (ICM), Univ. Montpellier, Montpellier, France; Institut régional du Cancer de Montpellier (IRCM), INSERM, Univ. Montpellier, ICM, Montpellier.

Background: No treatment option was available for patients with RAS-mutated (RASmt) metastatic colorectal cancer (mCRC) who progress after standard combined chemotherapies at the time of the study. After promising results in phase II, the aim of the present NEXIRI-2/PRODIGE 27 trial was to assess the 2-month non-progression rate for sorafenib (NEX) plus irinotecan (IRI), that is, NEXIRI, treatment.

Methods: Patients with RASmt mCRC after failure of oxaliplatin, IRI, fluoropyrimidines, and bevacizumab were randomized between NEXIRI (IRI 120-180 mg/m intravenous, D1 = D15 plus oral NEX 400 mg twice a day) versus IRI (180 mg/m) versus NEX. Primary endpoint was the 2-month non-progression rate. Secondary endpoints included progression-free and overall survival (PFS and OS), safety, and germline cyclin D1 (CCND1) rs9344 polymorphisms analyses.

Results: A total of 173 patients were included, 59 in NEXIRI, 57 in IRI, and 57 in NEX arms. The 2-month non-progression rate was 52.6% (95% confidence interval [CI]: 39%-66%), 21.4% (10%-33%), and 19.3% (9%-30%) for NEXIRI, IRI, and NEX. Median PFS was 3.6 (95% CI: 2-4.2), 1.7 (1.7-1.8), and 2 (1.8-2.3) months and the median OS was 7.2 (5.8-9.4), 6.3 (4.8-8), and 5.6 (3.9-7.7) months for NEXIRI, IRI, and NEX, respectively. For NEXIRI rs9344CCND1 A/A genotype patients, OS was 19.6 months (95% CI: 4.8-not reached). Main grade 3 toxicities included neutropenia, febrile neutropenia, diarrhea, hand-foot syndrome, and hypertension.

Conclusions: In patients with RASmt mCRC who progressed after standard combined chemotherapies, the results of 2-month non-progression rate and median PFS in the NEXIRI arm were in favor of an increase of the time before progression.
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http://dx.doi.org/10.1016/j.clcc.2020.04.008DOI Listing
December 2020

Complete Metabolic Response Assessed by FDG PET/CT to FOLFOXIRI-Bevacizumab in First-Line Treatment of BRAFV600E Mutated Metastatic Colorectal Cancer.

Clin Nucl Med 2020 Sep;45(9):707-708

From the Departments of Oncology.

Triplet chemotherapy (FOLFOXIRI) + bevacizumab regimen is indicated as first-line treatment of BRAF-mutated metastatic colorectal cancer (mCRC). Nevertheless, its proven therapeutic efficacy in clinical trials was solely based on partial morphologic responses assessed by CT. To date, only 1 case of complete response assessed by FDG PET/CT was reported in literature in BRAF-mutated mCRC, but treated with doublet chemotherapy (FOLFIRI) + cetuximab regimen. We report a complete metabolic response assessed by FDG PET/CT, maintained over time (13 months) in a 60-year-old woman with BRAF-mutated mCRC treated by FOLFOXIRI-bevacizumab. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.
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http://dx.doi.org/10.1097/RLU.0000000000003190DOI Listing
September 2020

Circulating Tumor DNA is Prognostic and Potentially Predictive of Eryaspase Efficacy in Second-line in Patients with Advanced Pancreatic Adenocarcinoma.

Clin Cancer Res 2020 Oct 30;26(19):5208-5216. Epub 2020 Jun 30.

Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France.

Purpose: Eryaspase is composed of l-asparaginase encapsulated in erythrocytes and has demonstrated significant efficacy in a randomized phase II trial. We assessed the prognostic and predictive value of circulating tumor DNA (ctDNA) in patients, plasma included in this trial.

Experimental Design: Samples prospectively collected pretreatment were centrally analyzed by next-generation sequencing. Prognostic values of baseline ctDNA and ctDNA early changes between day 0 and 28 were assessed in both arms combined on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS); three groups were defined: negative ctDNA (Neg), ctDNA responders (Resp), and ctDNA nonresponders (NResp). Predictive value of ctDNA for eryaspase efficacy was investigated.

Results: ctDNA was positive at baseline in 77 patients of the 113 tested patients (68%). Detectable ctDNA was an independent negative prognostic factor for OS (4.6 vs. 8.8 months; = 0.0025) and PFS (1.6 vs. 3.3 months; = 0.00043). Early change in ctDNA levels was correlated with ORR (20%, 26%, 0%; < 0.04), PFS (3.7, 3.4, 1.6 months; < 0.0001), and OS (11.7, 6.5, 4.3 months; < 0.0001) according to the three defined groups (Neg, Res, NResp, respectively). In patients with ctDNA detectable at baseline, eryaspase was associated with better PFS [HR = 0.53; 95% confidence interval (CI): 0.3-0.94)] and OS (HR = 0.52; 95% CI: 0.29-0.91).

Conclusions: We confirm from a prospective randomized trial that: (i) the presence of ctDNA at baseline is a major prognostic factor, (ii) the early change of ctDNA correlates with treatment outcome, and (iii) the ctDNA could be a predictive biomarker of eryaspase efficacy.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0950DOI Listing
October 2020

Implementation of a molecular tumor board at a regional level to improve access to targeted therapy.

Int J Clin Oncol 2020 Jul 25;25(7):1234-1241. Epub 2020 Mar 25.

Centre Eugene Marquis, Unicancer, Rennes, France.

Background: With the development of precision oncology, Molecular Tumor Boards (MTB) are developing in many institutions. However, the implementation of MTB in routine clinical practice has still not been thoroughly studied.

Material And Methods: Since the first drugs approved for targeted therapies, patient tumor samples were centralized to genomic testing platforms. In our institution, all tumor samples have been analyzed since 2014 by Next Generation Sequencing (NGS). In 2015, we established a regional MTB to discuss patient cases with 1 or more alterations identified by NGS, in genes different from those related to drug approval. We conducted a retrospective comparative analysis to study whether our MTB increased the prescriptions of Molecular Targeted Therapies (MTT) and the inclusions of patients in clinical trials with MTT, in comparison with patients with available NGS data but no MTB discussion.

Results: In 2014, 86 patients had UGA, but the results were not available to clinicians and not discussed in MTB. During the years 2015 and 2016, 113 patients with an UGA (unreferenced genomic alteration) were discussed in MTB. No patients with an UGA were included in 2014 in a clinical trial, versus 2 (2%) in 2015-2016. 13 patients with an UGA (12%) were treated in 2015-2016 with a MTT whereas in 2014, no patient (p = 0.001).

Conclusions: In this retrospective analysis, we showed that the association of large-scale genomic testing and MTB was feasible, and could increase the prescription of MTT. However, in routine clinical practice, the majority of patients with UGA still do not have access to MTT.
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http://dx.doi.org/10.1007/s10147-020-01661-6DOI Listing
July 2020

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Oncologist 2020 02 2;25(2):e266-e275. Epub 2019 Oct 2.

Department of Gastroenterology, Cochin Hospital, Paris, France.

Background: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.

Materials And Methods: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).

Results: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).

Conclusion: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.

Implications For Practice: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
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http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI)-PRODIGE 62: A multicentre, randomised, non-comparative phase II study.

Dig Liver Dis 2020 03 30;52(3):347-350. Epub 2019 Dec 30.

Gastroenterology Department, Centre Hospitalo-Universitaire de Poitiers, University of Poitiers, Poitiers, France. Electronic address:

Half of patients newly diagnosed with esophageal squamous cell cancer (ESCC) have metastatic disease (mESCC) and therefore a poor prognosis. Furthermore, half of patients with initial loco-regional disease present disease recurrence after surgery and/or chemoradiation. In mESCC, the recommended first-line treatment combines 5-fluorouracil and cisplatin, although this has not been validated by a phase III trial. Patients with disease progression or recurrence after platinum-based chemotherapy and good performance status probably benefit from second-line chemotherapy. Several molecules have been evaluated in phase I/II trials or retrospective studies (docetaxel, paclitaxel and irinotecan) but no randomised studies are available. OESIRI is a multicentre, randomised, open-label phase II trial designed to evaluate efficacy and safety of liposomal irinotecan (nal-IRI) plus 5-FU versus paclitaxel as second-line therapy in patients with mESCC. The main inclusion criteria are histologically proven mESCC in progression after first-line platinum-based chemotherapy. Patients with initial resectable disease can be included if recurrence occurred within 6 months. The primary objective is to evaluate the percentage of patients alive 9 months after randomisation. Secondary endpoints are progression-free survival, overall survival, response rate, safety and quality of life. In addition, circulating tumour DNA will be monitored to assess its prognostic value.
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http://dx.doi.org/10.1016/j.dld.2019.11.014DOI Listing
March 2020

Complete Metabolic Response Assessed by FDG PET/CT to Paclitaxel-Ramucirumab in Patients With Metastatic Gastroesophageal Junction Cancer.

Clin Nucl Med 2020 Feb;45(2):127-128

From the Department of Oncology, University Hospital of Brest.

Paclitaxel-ramucirumab chemotherapy is indicated in second line of metastatic gastroesophageal junction cancer (mGEJC) after progression under platinum-5-FU chemotherapy. Nevertheless, the reported common response after treatment is only partial within series. To date, only 1 case report of negative posttreatment FDG PET/CT was published without baseline examination from RAINBOW trial. We illustrated the interest of FDG PET/CT to evaluate treatment especially paclitaxel-ramucirumab with 2 examples of complete metabolic responses in 2 patients having different HER2 biomarker profiles of mGEJC. As illustrated, FDG PET/CT emerges as a useful approach for therapeutic assessment of targeted drugs in mGEJC.
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http://dx.doi.org/10.1097/RLU.0000000000002882DOI Listing
February 2020

Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial.

Eur J Cancer 2020 01 21;124:91-101. Epub 2019 Nov 21.

ERYTECH, One Main Street, Suite 1150, Cambridge, MA 02142, USA.

Purpose: This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma.

Methods: Eligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression. Secondary endpoints included OS and PFS in the entire population.

Results: 141 patients were randomized (eryaspase arm, n = 95; control arm, n = 46). Median OS and PFS in patients with low ASNS expression were 6.2 months (95% CI, 5.1-8.8) in the eryaspase arm versus 4.9 months (3.1-7.1) in the control arm (HR, 0.63; 95% CI, 0.39-1.01; P = 0.056) and 2.0 months (95% CI, 1.8-3.4) in the eryaspase arm versus 1.8 months (1.4-3.8) in the control arm (HR, 0.67; 95% CI, 0.40-1.12; P = 0.127), respectively. In the entire population, median OS and PFS for the eryaspase arm versus control were 6.0 months versus 4.4 months (HR, 0.60; P = 0.008) and 2.0 months versus 1.6 months (HR, 0.56; 95% CI, 0.37-0.84; P = 0.005), respectively. The combination of eryaspase and chemotherapy was well tolerated. The most frequent Grade 3/4 adverse events in the eryaspase arm (n = 93) were gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), and physical health deterioration (12 [12.9%]).

Conclusion: Eryaspase in combination with chemotherapy is associated with improvements in OS and PFS, irrespective of ASNS expression in second-line advanced pancreatic adenocarcinoma. A Phase III trial is underway.
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http://dx.doi.org/10.1016/j.ejca.2019.10.020DOI Listing
January 2020

Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational CORRELATE study.

Eur J Cancer 2019 12 4;123:146-154. Epub 2019 Nov 4.

Department of Medical Oncology, University of Pisa, Pisa, Italy.

Background: Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice.

Methods: The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03).

Results: A total of 1037 patients were treated. The median age was 65 years (range: 24-93); 87% of patients had Eastern Cooperative Oncology Group performance status 0-1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand-foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2-8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8-3.0).

Conclusions: In this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials.

Trial Registration: NCT02042144.
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http://dx.doi.org/10.1016/j.ejca.2019.09.015DOI Listing
December 2019

[Management of cancer patients with oral therapy at home in Brittany and Pays de la Loire areas: Survey (end of 2016) and cartography].

Bull Cancer 2019 Oct 11;106(10):847-859. Epub 2019 Sep 11.

Centre Jean-Bernard/clinique Victor-Hugo, Le Mans, 18, rue Victor-Hugo, 72000 Le Mans, France.

Introduction: The Cancer Observatory, from the OMEDITs (Observatory for Medicines and Medical Devices and Treatment Innovations) of Bretagne and Pays de la Loire areas has conducted a survey aiming to know and map the current practices of management of patients by Oral Anti-cancer Drug (OAD) in inter-region.

Methods: Forty eight cancer centers received by e-mail in July and October 2016 a questionnaire concerning the management of OADs : from prescription by the specialist of oncology, to the intervention of the pharmacist (analysis and pharmaceutical consulting), to follow-up by nurse, as well as the financing of this activity and the feelings of the actors about this organizational set up.

Results: Fifty-seven professionals from 31 centers, including the most important ones, responded to the survey. As a result, half of the establishments carry out a pharmaceutical analysis for some or all of the OAD prescriptions and only 30% carry out a pharmaceutical consulting. The nurse consultation is, on the other hand, more largely implanted (74% of the centers) as well as the telephone follow-up (6%). More than 90% of professionals believe that the organizational set up could be improved and more secure by, at least, the stronger involvement of pharmacists, the development of tools for nurse (for monitoring, therapeutic education…) and by improving the city-hospital link.

Conclusion: This survey shows the variability in the management of patients under OAD because of the lack of resources to ensure the fairness and sustainability of the organizational set up. The hospital/city link could still be optimized to secure patient care.
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http://dx.doi.org/10.1016/j.bulcan.2019.05.012DOI Listing
October 2019

Complete Metabolic Response Assessed by FDG PET/CT to FOLFIRI-Aflibercept in Second-Line Treatment of Metastatic Colorectal Cancer.

Clin Nucl Med 2019 Jul;44(7):578-579

From the Departments of Oncology.

FOLFIRI-aflibercept chemotherapy is indicated in second-line treatment of metastatic colorectal cancer (mCRC) after progression under FOLFOX (±bevacizumab). Nevertheless, its proven therapeutic efficacy in clinical trials was based on partial responses. And to date, only 2 cases of complete response assessed by CT were reported in literature. We report a complete metabolic response assessed by FDG PET/CT in a 50-year-old woman with mCRC treated by FOLFIRI-aflibercept. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.
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http://dx.doi.org/10.1097/RLU.0000000000002611DOI Listing
July 2019

Real-world incidence of cancer following a first unprovoked venous thrombosis: Results from the EPIGETBO study.

Thromb Res 2018 04 2;164:79-84. Epub 2018 Mar 2.

EA 3878 (GETBO), Brest University, 29200 Brest, France; INSERM CIC 1412, Hôpital de la Cavale Blanche, 29609 Brest Cedex, France.

Background: Venous thromboembolism (VTE) can be the first manifestation of cancer; however, the current incidence of malignancy in unselected patients with first unprovoked VTE needs to be confirmed.

Material And Methods: Between March 1st, 2013 and February 28th, 2015 we included and followed-up all patients living in the Brest district, France, who were seen in hospitals or the community for a first symptomatic unprovoked VTE event. The primary study outcome was the one-year incidence of cancer.

Results: 526 patients, mean age 66.6 ± 18.1 years, 246 (46.8%) men, were included in the study. In the year following VTE, 26 patients were diagnosed with cancer, corresponding to a one-year cumulative incidence of cancer of 5.06% (95% CI 3.47-7.35). Age ≥60, smoking and pulmonary embolism were significantly associated with cancer diagnosis in multivariate analysis. Fifty percent of cancers were patent at the time of VTE diagnosis, mostly detected on CTPA (Computed Tomographic Pulmonary Angiography) performed for pulmonary embolism assessment. After excluding patients with patent cancer at VTE diagnosis, the one-year incidence of cancer was 2.65% (95% CI: 1.55-4.52); in multivariate analysis, only current smoking was independently associated with a significant 5.4-fold increased risk for cancer diagnosis (HR 5.40; 95% CI 1.31-22.27). No cancer was diagnosed in patients aged 50 years or younger.

Conclusion: The one-year incidence of cancer after a first unprovoked VTE was 5.06%. Half of the cancers were diagnosed during the diagnosis procedure for pulmonary embolism using CTPA.
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http://dx.doi.org/10.1016/j.thromres.2018.02.151DOI Listing
April 2018

In reply.

Semin Oncol 2017 04 4;44(2):161. Epub 2017 Aug 4.

Oncopharmacologie, ICO Paul Papin, Angers, France; Service d'Oncologie Médicale, ICO Paul Papin Angers, France; Service de Gastro-Entérologie, Centre Hospitalier Départemental Les Oudairies, La Roche sur Yon, France; Service d'Oncologie Médicale, CHU Jean Minjoz, Besançon, France; Service d'Oncologie et de Radiothérapie, Institut de Cancérologie et d'Hématologie, Brest, France; Service d'Oncologie Médicale, Centre François Baclesse, Caen, France; Service d'Hépatologie et de Gastroentérologie, Centre Hospitalier, Cholet, France; Service d'Oncologie Médicale, ICO René Gauducheau, Saint Herblain, France; Service d'Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire, Caen, France; Service d'Hépato-Gastro-Entérologie, Centre A. Lacassagne, Nice, France; Service d'Oncologie Médicale, Hôpital Henri Mondor, Creteil, France; Service d'Oncologie Médicale, Centre Hospitalier, Saumur, France; Service d'Onco-Hématologie, Centre Hospitalier, LeMans, France; Service d'Oncologie Médicale, Clinique Gentilly, Nancy, France; Service d'Hépato-Gastro-Entérologie, Proctologie et Oncologie Digestive 5B, Centre Hospitalier, Laval, France; Unité d'Hépato-Gastro-Entérologie,Centre Hospitalier Sartheet Loir, LaFleche, France; Service d'Hépato-Gastro-Entérologie, CHU Hôpital Trousseau, Tours, France; Centre Evaluation Clinique, ICO Paul Papin, Angers, France.

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http://dx.doi.org/10.1053/j.seminoncol.2017.08.002DOI Listing
April 2017

A multicenter phase II study of personalized FOLFIRI-cetuximab for safe dose intensification.

Semin Oncol 2017 Feb 9;44(1):24-33. Epub 2017 Feb 9.

Oncopharmacology - Pharmacogenetics Department INSERM U892, Institut de Cancérologie de l'Ouest site Paul Papin, Angers, France.

We conducted a multicenter proof of concept phase II trial in patients with advanced colorectal cancer receiving FOLFIRI-cetuximab regimens to explore individual drug tailoring using pharmacogenetics and pharmacokinetics (PK) monitoring. Patients were stratified by their pharmacogenetic/phenotypic status: the irinotecan dose was adjusted according to the number of TA tandem repeats in the UGT1A1 promoter, while the 5-fluorouracil (5-FU) dose was initially adjusted according to dihydropyrimidine dehydrogenase (DPD) activity at initial screening (5-FU) followed by PK-guided dose optimization (5-FU). An advanced cetuximab PK/pharmacodynamics (PD) study was performed but dosage remained unchanged. Eighty-five patients receiving second-line chemotherapy were enrolled. Mean irinotecan doses at 3 months were 247 ± 50, 210 ± 53 and 140 ± 21 mg/m for those with 6/6 (33), 6/7 (26), and 7/7 (7) TATA repeats in the UGT1A1 promoter region, respectively. The 5-FU dose was initially reduced in four patients with DPD deficiency, but mean 5-FU dose at 3 months was 2,412 ± 364 mg/m (1,615-3,170 mg/m). Grade 4 toxicities were not encountered and grade 4 neutropenia occurred in 6.8%, 5.9%, and 0% of patients with 6/6, 6/7, and 7/7 UGT1A1 genotypes. The objective response rate was 25.8% among the 85 patients, 57.3% in patients with tumors wild type (WT) for KRAS, and 25% in those whose tumor harbored a mutant-KRAS. Secondary resection of hepatic metastases was performed in 31.7% of patients. Median progression-free survival (PFS) for all 85 patients was 181 days and 200, 132, and 121 days for patients with 6/6, 6/7, and 7/7 UGT1A1 genotypes, respectively; these differences were not statistically different. In parallel, a strong relationship was shown between cetuximab AUC and regimen efficacy. We conclude that personalized drug tailoring when administering in FOLFIRI + cetuximab allows for safe and efficient individual dose intensification.
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http://dx.doi.org/10.1053/j.seminoncol.2017.02.007DOI Listing
February 2017

Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach.

Semin Oncol 2017 Feb 11;44(1):13-23. Epub 2017 Feb 11.

Oncopharmacologie, ICO Paul Papin, Angers, France.

5-Fluorouracil (5-FU)-based treatments can lead to early-onset severe (4%-5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pretherapeutic screening for DPD deficiency using a multiparametric approach. Two parallel cohorts of patients treated with 5-FU-based chemotherapy for colorectal carcinoma were compared in a prospective nonrandomized study. In arm A, patients had DPD deficiency screening before treatment, whereas in arm B no pretherapy screening was performed. Dosing was based on 5-FU administration guidelines of each institution. DPD deficiency screening was performed using a combined multiparametric approach (5-FU). The frequency of early grade 4-5 toxic events potentially induced by 5-FU was compared in the two groups. At total of 1,142 patients (n = 1,116 evaluable) were enrolled. In arm A, out of 718 evaluable patients, nine grade 4 early toxicities potentially related to 5-FU were reported in nine patients (1.2%) with no toxic death despite one complete DPD deficiency and 24 partial deficiencies. The 24 patients with partial deficiency had safe pharmacokinetics (PK)-monitored 5-FU. In arm B, among 398 evaluable patients, 17 grade 4-5 toxic early events potentially related to 5-FU were reported in 12 patients (4.2%). The incidence of early severe toxicity was significantly higher in arm B (P = .0019), confirming the positive impact of pretherapeutic DPD assessment. The percent of patients with a toxicity grade 3 or higher observed in arm A was 10.8% (n = 78) compared to 17.55% (n = 69)  in arm B (P = .0497). The percentage of death was reduced from 2.5/1,000 in arm B to 0 in arm A. The time to occurrence of all grade ≥3 toxicities was determined in both arms and the difference between the two arms was significant (P = .047). Overall, one patient with complete DPD deficiency confirmed retrospectively died within 13 days from grade 5 multivisceral toxicity. Enrollment was prematurely closed after external experts' decision. In conclusion, multiparametric pretherapeutic DPD deficiency screening significantly lowered the risk of early severe toxicity and avoided an early toxic death. This approach should be used for safe administration of 5-FU-based treatments.
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http://dx.doi.org/10.1053/j.seminoncol.2017.02.008DOI Listing
February 2017

External validation of the modified Ottawa score for risk stratification of recurrent cancer-associated thrombosis.

Eur J Intern Med 2016 Dec 31;36:e11-e12. Epub 2016 Aug 31.

Department of Internal Medicine and Chest Diseases, Brest University Hospital, Brest F-29609, France; Brest University (Université de Bretagne Occidentale), Groupe d'Etude de la Thrombose de Bretagne Occidentale, Equipe d'Accueil 3878, Brest F-29609, France.

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http://dx.doi.org/10.1016/j.ejim.2016.08.001DOI Listing
December 2016

Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial).

Cancer Chemother Pharmacol 2016 Apr 10;77(4):819-27. Epub 2016 Mar 10.

Institut Català d'Oncologia (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

Purpose: To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.

Methods: Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.

Results: Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.

Conclusions: Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.
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http://dx.doi.org/10.1007/s00280-016-2991-0DOI Listing
April 2016

[Optimizing good use and costs of anticancer drugs: A French inter regional study of the Observatory of Cancer].

Bull Cancer 2013 Mar;100(3):271-82

Observatoire dédié au Cancer Bretagne et Pays-de-la-Loire, Siège médical Paul-Papin, 49000 Angers, France.

Optimizing the care management of patients is a major issue for our society. In Brittany-Pays-de-la-Loire (almost 10% of French population), an observatory of cancer has been created in 2003. Its main objective was the follow-up of expensive drugs. The knowledge of the use of these drugs in clinical practice has led to development of a thesaurus of good use. Thus, regular exchanges between clinicians have almost totally reduced not medically justified prescriptions by the thesaurus after and before administration to patient. The thesaurus has given away to national guidelines from 2007. For example, in these two regions, optimization of the use of gemcitabine and bevacizumab has allowed to save respectively 2.5 millions euros between 2005 and 2008 and 3 millions euros between 2009 and 2010 (breast cancer only). Optimizing the use of anticancer drugs has allowed a real health economy without any bad impact on patient management. Respecting medical ethics, the main objective remains to optimize health care. This highly participation of clinicians currently allows to reflect together on the relevance of the last chemotherapy.
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http://dx.doi.org/10.1684/bdc.2013.1715DOI Listing
March 2013

[HER2 and gastric cancer. Recommendations for clinical practice in 2011].

Ann Pathol 2011 Apr 7;31(2):78-87. Epub 2011 May 7.

Département de pathologie, centre Jean-Perrin, BP 392, 58, rue Montalembert, 63011 Clermont-Ferrand cedex, France; EA 4233, université d'Auvergne, 63000 Clermont-Ferrand cedex, France.

Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin has been approved by the European Medicines Agency (EMEA) for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry [IHC] 3+ or IHC 2+/ fluorescence in situ hybridization [FISH]-positive or IHC 2+/ silver in situ hybridization [SISH]-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal (GE) junction. HER2 testing in gastric cancer (GC) differs from testing in breast cancer (BC) due to major differences in the tumor biology; as the disease is progressing rapidely, we recommend to test every GC at diagnosis and to offer a rapid testing (less than five days) in the metastatic setting. IHC should be the initial testing methodology and FISH or SISH should be used to retest IHC 2+ samples. As GC more frequently shows incomplete membrane staining and focal staining for HER2, HER2 testing guidelines have been adapted from BC protocols. The scoring system is slightly different in respect to the characteristics of GC. For in situ hybridization, SISH should be used in order to identify heterogeneous staining with a higher accuracy than FISH. Enrollment in training and quality assurance programs is highly recommended. In case of negativity on biopsy, it is recommended to retest for HER2, when possible, on surgical specimens and/or metastasis. This will ensure accurate and consistent HER2 testing results, which will allow the appropriate selection of patients eligible for treatment with trastuzumab.
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http://dx.doi.org/10.1016/j.annpat.2011.03.001DOI Listing
April 2011

Trends in incidence, management, and survival of gastric and cardia carcinomas in the area of Finistere (France) between 1984 and 2003.

Eur J Gastroenterol Hepatol 2010 Dec;22(12):1412-9

Department of Hepato-Gastroenterology, Brest University Hospital of Finistère, Brest, France.

Objective: The aim of this study was to evaluate trends in incidence and prognosis of gastric and cardia carcinomas in the area of Finistère (France) between 1984 and 2003.

Methods: The Digestive Tumor Registry of Finistère recorded all new cases of gastric and cardia carcinomas from January 1, 1984 to December 31, 2003. Raw incidence data were standardized using the direct method based on the reference world population. The data and survival rates were studied in univariate and multivariate analyses.

Results: Between 1984-1988 and 1999-2003 the standardized incidence of distal gastric carcinomas decreased (10.74 ± 0.39-5.68 ± 0.27/year/100 000 inhabitants, P < 0.001). There was no significant increase in the incidence of cardia carcinomas (0.83 ± 0.11-1.25 ± 0.14/year/100 000 inhabitants). The frequency of macroscopically infiltrating tumors doubled (P < 0.001) and linitis plastica increased from 9 to 16.2% (P < 0.001). Overall survival rates increased only for patients with metastatic carcinomas of both locations (P < 0.001) and with advanced tumors of distal stomach (P < 0.001) receiving therapy.

Conclusion: This study showed a significant decrease over time in the incidence of distal gastric carcinomas but no significant increase in the incidence of cardia carcinomas. Despite improvement in the management of patients, prognosis remains dismal, probably because of an increased incidence of poor prognosis of histological and anatomical types.
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http://dx.doi.org/10.1097/MEG.0b013e3283408865DOI Listing
December 2010