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Background: The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup)., Patients and Methods: Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan)., Results: The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores., Conclusions: As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors have failed in treating metastatic colorectal cancer (mCRC) patients except those with dMMR/MSI tumors. However, until very recently we had only non-comparative promising data in this population with anti-programmed cell death 1/ programmed cell death ligand 1 (PD1/PD-L1) antibodies alone or combined with anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies. This comparative phase II trial (NCT03186326), conducted in more than 100 centers in France, will include dMMR/MSI mCRC patients with progression after a first-line treatment with chemotherapy ± targeted therapies, to evaluate efficacy and safety of the anti-PDL1 Avelumab versus a standard second-line treatment. Main inclusion criteria were patients aged 18 to 75 years, ECOG performance status ≤2, dMMR/MSI mCRC and failure of a standard first-line regimen. Patient will be randomised to receive Avelumab 10 mg/kg versus standard second-line doublet chemotherapy plus a targeted agent according to tumor RAS status. Patients will be followed for 4 years. A gain of 5 months in median PFS is expected in favour of the Avelumab arm (12 vs 7 months; HR=0.58). Secondary endpoints include objective response rate, overall survival, quality of life and toxicity. In addition, circulating tumour DNA and microbiota will be explored to test their potential prognostic and predictive values. The study was opened in March 2018., Competing Interests: Declaration of Competing Interest JT has received honoraria for speaker or advisory role from Sanofi, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, Lilly, Astra Zeneca and MSD. LE has received honoraria for speaker or advisory role Servier, Merck Serono, Amgen. PLP is a consultant/advisory board member for Merck Serono, Astrazeneca Amgen, Boehringer Ingelheim, Biocartis, Roche, Bristol-Myers Squibb, Pierre Fabre, Servierand MSD. CL has served in a consulting/advisory role and or received honoraria for, Amgen, Pierre Fabre, Novartis, AAA. FE has received honoraria for speaker and/or advisory role from Ipsen, Merck, Bayer, Sanofi and Servier. OB has received honoraria for speaker and/or advisory role from Merck KGaA, Roche Genentech, Bayer, Astra-Zeneca, Grunenthal, MSD, Amgen, Servier, and Pierre Fabre, TA has served in a consulting/advisory role and/or received honoraria from Amgen, Bristol-Myers Squibb, Chugai, Clovis, Halliodx, MSD, Pierre Fabre, Roche/Ventana, Sanofi, Servier and has received travel, accommodations, and expenses from Roche/Ventana, MSD Oncology, and Bristol-Myers Squibb. DT has served in a consulting/advisory role and/or received honoraria from Amgen, Bristol-Myers Squibb, MSD Oncology, Roche/Ventana, Sanofi, Servier, Novartis, Merck Serono and Astra Zeneca. HP has served in a consulting/advisory role and/or received honoraria from Amgen, Sanofi, Servier, Merck Serono and Roche. SK has received honoraria for speaker and/or advisory role from Amgen, Ipsen, MSD, Pfizer, Sanofi, and Servier. EB, JFE, JB, MC and FD have nothing to disclose. CT has received honoraria for speaker or advisory role from Merck, Sanofi, MSD, Ipsen, Amgen, Servier, and Bristol-Myers Squibb. This research was financially supported by Merck Santé S.A.S., an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Primary neuroendocrine breast carcinomas are rare and little-known tumors. Only a limited number of studies on neuroendocrine breast carcinomas have been reported in the literature, and the vast majority of them are small retrospective series or case reports. According to the World Health Organization (WHO), they account for only 2 % to 5 % of breast cancers. Their diagnosis relies on the presence of a neuroendocrine architecture and the expression of neuroendocrine markers (chromogranin A and/or synaptophysin). The revised 2012 WHO classification subdivides them into three categories: (i) well-differentiated neuroendocrine carcinomas, (ii) poorly differentiated neuroendocrine carcinomas or small-cell carcinomas, and (iii) invasive breast carcinomas with neuroendocrine differentiation. Their clinical features and radiological characteristics are not different from those of other types of breast cancer. Because of discordant results, their clinical outcome is still poorly defined. So far, no standard treatment has been established, and most clinicians draw on their experience of invasive ductal cancer. The role of specific treatments like platinum-based chemotherapy, somatostatin analogues, peptide receptor radionucleide therapy or temozolomide remains unclear. A better knowledge of the molecular pathways involved in their carcinogenesis could help to identify new potential therapeutic targets. The efficacy of targeted therapies has to be studied., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab., Patients and Methods: We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated., Results: With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC., Conclusion: DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population., Patients and Methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria., Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT)., Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Malignant ascites, occurring in advanced stages of cancer, is linked with poor prognosis and can cause invalidating symptoms. Physiopathological mechanisms of ascites formation are complex and have yet to be fully elucidated. In most cases, ascites is due to peritoneal carcinomatosis in which vascular permeability is enhanced by VEGF production while lymphatic drainage decreases. Ascites can also be secondary to portal hypertension, for example in case of multiple liver metastases, or due to lymphatic obstruction. While paracentesis and diuretics are commonly used, their efficiency has never been compared in a randomized controlled study. Paracentesis brings immediate but temporary relief in over 90% of cases, and implies multiple hospitalizations. Literature reports ascites control by aldosterone alone or in association with furosemide. But, available data is controversial, and there is no predictive factor to identify patients that respond to diuretic treatment. The indication of diuretic treatment is left to the appreciation of physicians. Existing recommendations are old, and practices influenced by results obtained in non-neoplastic ascites. Additional evidences are required before guidelines can be established for the palliative management of malignant ascites., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)