0000000000307154
AUTHOR
Karine Le Malicot
PRODIGE 59-DURIGAST trial: A randomised phase II study evaluating FOLFIRI + Durvalumab ± Tremelimumab in second-line of patients with advanced gastric cancer
International audience; Gastric or gastro-oesophageal junction (GEJ) adenocarcinomas present poor overall survival (OS). First-line chemotherapy regimen for patients with HER2-negative tumours is based on a doublet or triplet of fluoropyrimidine plus platinum salt ± taxane. Second-line chemotherapy (Docetaxel or Irinotecan) improves OS which nonetheless remains poor (around 5 months). The first results of immune checkpoint inhibitors (anti-PD-1) combined with chemotherapy in metastatic gastric and GEJ cancers were discordant in recent phase III trials. Data on dual-blockade (anti-PD-L1 or anti-PD-1 plus anti-CTLA-4) plus chemotherapy are lacking. DURIGAST is a randomised, multicenter, non-c…
Construction of quality of life change patterns: example in oncology in a phase III therapeutic trial (FFCD 0307)
Objective Quality of life data in cancerology are often difficult to summarize due to missing data and difficulty to analyze the pattern of evolution in different groups of patients. The aim of this work was to apply a new methodology to construct Quality of Life (QoL) change patterns within patients included in a clinical trial comparing to regimen of treatment in locally advanced eosogastric cancer. Materials and methods In this trial, QoL was assessed every 2 months by self-reported EORTC QLQ-C30 questionnaire. Physical dimension scores were analyzed. After multiple imputation of missing data, 27 statistical measures aiming to describe the variation of QoL measures among follow-up were c…
Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)
Abstract Background FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line. Patients and Methods Patients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H0: 55% and H1= 75%. Data were analyzed …
Decision for adjuvant treatment in stage II colon cancer based on circulating tumor DNA:The CIRCULATE-PRODIGE 70 trial
International audience; Background: Adjuvant treatment for stage II colon cancer remains debated. Finding a tool to select patients at risk for disease recurrence may help the clinical decision. Circulating tumor DNA (ctDNA) has been reported recently as a potential predictive marker for disease recurrence. We thus aim to test its ability to better select stage II colon cancer patients for adjuvant therapy.Methods: This national, phase III trial (NCT00002019-000935-15) conducted in more than 100 centers in France, plans to screen around 2640 patients in order to randomize (2:1; minimization method) 198 ctDNA positive patients. Patients aged 18 to 75 years with ECOG performance status ≤1 wit…
Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma
Background: Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan. Methods: This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined. Results: Baseline splenic volume >
Analyse des infiltrats immunitaires CD3 et CD8 chez 1280 malades atteints de cancers coliques de stade III : approche par intelligence artificielle entièrement automatisée
L’etude retrospective de tumeurs par immunohistochimie constitue un enjeu majeur dans l’amelioration de la prise en charge atteints de pathologies cancereuses. Cependant l’analyse est chronophage pour le pathologiste et reste le plus souvent semi-quantitative pouvant entrainer une perte d’information. L’intelligence artificielle, qui consiste en une approche d’analyse automatisee a haut debit, pourrait permettre de s’affranchir dans ce contexte du pathologiste en apportant de plus une information quantitative. Nous avons ainsi etudie deux parametres immunitaires, CD3 et CD8 sur 1280 lames de malades de la cohorte PETACC8 [1] , une etude europeenne de patients atteints de cancers coliques de…
Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer
Abstract Purpose: The consensus molecular subtypes (CMS) represent a significant advance in the understanding of intertumor heterogeneity in colon cancer. Intratumor heterogeneity (ITH) is the new frontier for refining prognostication and understanding treatment resistance. This study aims at deciphering the transcriptomic ITH of colon cancer and understanding its potential prognostic implications. Experimental Design: We deconvoluted the transcriptomic profiles of 1,779 tumors from the PETACC8 trial and 155 colon cancer cell lines as weighted sums of the four CMSs, using the Weighted In Silico Pathology (WISP) algorithm. We assigned to each tumor and cell line a combination of up to three …
Additional file 1: of Construction of quality of life change patterns: example in oncology in a phase III therapeutic trial (FFCD 0307)
Annex 1: The Full EORTC QLQ-C30 version 3 questionnaire with 30 items and their answer options. The physical functioning scale is concerned by items 1 to 5. Annex 2: Construction steps of quality of life change pattern from longitudinal data score, taking into account the presence of missing scores. Annex 3: Listing of the 27 statistical measures of change with in bold case (N°), the measures selected for the classification. Annex 4: The CritCF formula. (DOCX 568 kb)
Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial
PURPOSE Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4—ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC. METHODS In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternati…
Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19).
Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289…
Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study
Summary Background Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection. Aims We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure. Methods Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated. Results No bleeding complication was reported. One and two liver failures were respect…
Validation of the prognostic impact of lymphocyte infiltration (LI) in patients (pts) with stage III colon cancer (CC) treated with adjuvant FOLFOX plus /- cetuximab: A PETACC8 translational study
International audience; The prognostic value of LI of CC has been demonstrated by several groups. However no validated test is available for clinical practice. We previously described an automated and reproducible method for testing LI (Allard MA et al2012) and aimed to validate it for clinical use. Methods: According to NIH criteria, we designed a prospective analysis of this biomarker in pts included in the PETACC8 phase III study. Primary objective was to compare % of pts without recurrence at 2 years in pts with high versus low LI (#NCT02364024). Secondary objectives were comparison of disease free (DFS) and overall (OS) survivals, and prognostic value of LI on these endpoints. Automate…
Impact of laparoscopy on oncological outcomes after colectomy for stage III colon cancer: A post-hoc multivariate analysis from PETACC8 European randomized clinical trial
Abstract Background In colon cancer (CC), surgery remains the mainstay of treatment with curative intent. Despite several clinical trials comparing open and laparoscopic approaches, data on long-term outcomes for stage III CC are lacking. Methods This post-hoc analysis of the European PETACC8 randomized phase 3 trial included patients from 340 sites between December 2005 and November 2009, with long follow-up (median 7.56 years). Patients were randomly assigned to FOLFOX or FOLFOX+cetuximab after colonic resection. The surgical approach was left to the referring surgeon's discretion. Results Among 2555 patients included, 1796 (70.29%) were operated on by open surgery and 759 (29.71%) by lap…
Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX)
Abstract Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitab…
Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials
Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC).Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3).Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irino…
Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.
IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations…