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To examine the relationship between carcinoembryonic antigen (CEA) kinetics and prognosis in metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the PRODIGE9 trial. Associations between monthly CEA measurements within 6 months since baseline and progression-free survival (PFS) were evaluated using a joint-latent class-mixed model. A validation set was used to test our prognosis model. Correlations between CEA trajectories (classes) and baseline characteristics were also investigated. Three classes were identified. Class 1 had low baseline CEA with small variations. Class 2 had high baseline CEA with a rapid decrease reaching the same CEA level at 6 months as in class 1. Class 3 had high baseline CEA with a transient decrease followed by an increase to reach, at 6 months, the same CEA level as at baseline. Six-month PFS was significantly lower in class 3 than in classes 1 and 2 (57% vs. 91% and 93% respectively; p <0.01). Class 3 was significantly associated with ECOG 2 status, a high LDH level and non-resected primary tumor. Variations in CEA kinetics correlate with prognosis in patients receiving first-line chemotherapy for mCRC. We propose here a user-friendly application to classify CEA trajectory. [ABSTRACT FROM AUTHOR]

The COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the oldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer. From January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older referred to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose. Between January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose. Our study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients. Clinical trial registration : This study was registered May 23, 2019 in ClinicalTrials.gov (NCT03960593). [ABSTRACT FROM AUTHOR]

Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high". The first patient was included on April 20, 2021. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background This document is a summary of the French intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018. Design This collaborative work was produced under the auspices of all French medical and surgical societies involved in the management of PA. It is based on the previous guidelines, recent literature review and expert opinions. Recommendations were graded in three categories, according to the level of evidence. Results Over the last seven years, significant changes in PA management have been implemented in clinical practice. Imaging/staging: diffusion magnetic resonance imaging is useful before surgery to rule out small liver metastases. Surgery: centralization of pancreatic surgery in expert centers is associated with a decreased postoperative mortality. Adjuvant chemotherapy: modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine plus nab -paclitaxel combination are first-line standards in fit patients; second-line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line gemcitabine. Conclusion Guidelines for management of PA are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. However, as each individual case is particular, they cannot substitute to multidisciplinary tumor board discussion. [ABSTRACT FROM AUTHOR]

Introduction Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment. Aim PRODIGE 41–BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC. Materials and methods The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy. Results A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response. Conclusion The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017. [ABSTRACT FROM AUTHOR]

Introduction Biliary obstruction secondary to colorectal cancer liver metastases is associated with a poor prognosis especially when chemotherapy cannot be re-started. The aim of this study was to determine the survival after biliary drainage and the associated prognostic factors. Methods Patients from two French centers were included retrospectively after first biliary endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography drainage for biliary obstruction secondary to liver metastases of colorectal cancer, occurring during chemotherapy. Results The final analysis included 69 patients. Overall median survival was 115 days. In univariate analysis, a previous liver surgery, technical and functional success of drainage and restarted chemotherapy were significantly associated with an improved survival. Chemotherapy was restarted after a median of 27 days. When drainage was efficient, survival improved from 33 to 262 days (p < 0.001). In multivariate analysis, significant protective factors for survival included previous a hepatectomy (HR 0.41) and functional success of the drainage (HR 0.29). Predictive factors for death included increased lines of chemotherapy (HR 1.68) and fever before drainage (HR 2.97). Conclusions This is the first study concerning the benefits of biliary drainage for malignant biliary obstruction during the course of chemotherapy for colorectal cancer. A successful biliary drainage leads to improved survival and allows achievement of chemotherapy for 70% of patients. [ABSTRACT FROM AUTHOR]

Introduction Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30–50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained. Aim(s) The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET. Materials and methods Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization. Results 222 patients will be randomly assigned in a 1:1 ratio to receive 120 mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted. Conclusion The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377). [ABSTRACT FROM AUTHOR]

Oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. Two recent retrospective studies strongly suggested that low-dose aspirin used (100 mg/d) after surgical resection of colorectal cancer with a PIK3CA mutation could act as a targeted therapy with a major protective effect on the risk of recurrence. We propose a double-blind randomized phase III study to evaluate aspirin (100 mg/d during 3 years or until recurrence) versus placebo. Main inclusion criteria are patients aged 18 or 20, stage III or high risk stage II. The primary endpoint of the study is 3-year disease-free survival (DFS). Hypotheses are to improve 3-years DFS from placebo: 72% to aspirin: 83% (HR = 0.56). 94 events and 264 patients with PIK3CA mutation are required. The secondary endpoints are DFS at 5 years, the overall survival rate at 5 years, grade 3–4 severe bleeding. [ABSTRACT FROM AUTHOR]

Background No predictive marker has been yet identified for bevacizumab which is widely used in metastatic colorectal cancer. Aims Evaluate impact of single nucleotide polymorphisms involved in Vascular Endothelial Growth Factor pathway on efficacy and tolerance of bevacizumab. Methods We retrospectively included patients who were treated with bevacizumab-based chemotherapy for metastatic colorectal cancer, and for whom a deoxyribonucleic acid sample was available. Ten polymorphisms in Vascular Endothelial Growth Factor-A, his receptors and hypoxia inducible factor-1α were genotyped on germ line DNA using real-time polymerase chain reaction TaqMan ® . Results 89 patients were included. The CC genotype for rs3025039 ( Vascular Endothelial Growth Factor-A c.*237C>T) was associated with a significantly better time to treatment failure (14.2 months) as compared to the CT and TT genotypes (6.0 months) in univariate ( p = 0.004) and multivariate ( p = 0.022; HR = 0.57; 95% CI [0.35–0.92]) analysis. Patients with at least one T allele showed worse overall survival and progression-free survival as compared to homozygous CC patients in univariate analysis (respectively p = 0.016 and p = 0.044). There was significantly more severe hypertension for the CC genotype (29.5%) compared to CT and TT genotypes (7.1%) ( p = 0.022) in multivariate analysis. Conclusions In this retrospective study, the rs3025039 polymorphism was significantly associated with time to treatment failure and hypertension in patients treated with bevacizumab-based chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Chemotherapy combinations and addition of cetuximab or bevacizumab to chemotherapy have been shown to improve overall survival of metastatic colorectal cancer (CRC) patients. However, the efficacy of cetuximab when administered after bevacizumab failure is still unknown. Methods: Fifty-eight consecutive patients diagnosed with advanced colorectal cancer between treated with cetuximab following irinotecan failure were included in our analysis. A multivariate Cox model analysis was performed to estimate the effect of previous bevacizumab regimen on survival. Results: Thirteen (22.4%) were pre-treated with anti-VEGF agents. None of them responded to cetuximab, and this subgroup presented a significantly decreased disease-specific survival as compared to treatment-naïve patients (9.1 months vs. 4.9 months; p =0.026). This difference remained statistically significant in a multivariate Cox model after adjusting for age, sex, performance status (PS), and K-RAS status (RR=2.2; 95% CI: 1.1–4.5, p =0.03). Conclusion: These study results suggest that a previous anti-VEGF therapy decrease cetuximab efficiency. [Copyright &y& Elsevier]