Impact of open-label versus blinded study design on patient-reported outcomes data in randomized clinical trials of immunotherapy in advanced or metastatic cancer patients: a systematic review.

AIM: A systematic literature review of immuno-oncology trials was conducted to assess the potential impact of open-label vs double-blind trial design on patient-reported outcome (PRO) data. METHODS: A systematic search of indexed literature published from January 2009 to May 2019 was conducted using PubMed/MEDLINE, Cochrane Library, and EMBASE database. All randomized clinical trials (RCTs) of immuno-oncology therapies on advanced cancer patients reporting PRO data were identified. Descriptive analyses were performed to quantify differences at baseline and over time, by the type of study, regarding questionnaire completion rate and PRO scores. RESULTS: In total, 23 studies were retained (15 open-label, 8 blinded). At baseline, no difference in completion rate was observed between arms irrespective of trial design (absolute mean difference of 2.8% and 2.2% for open label and blinded studies, respectively). No clinically significant difference in baseline PRO scores was observed between arms. Over time, impact on PRO scores could not be identified due to the limited number of studies, heterogeneity of questionnaires and tumor types. CONCLUSIONS: Trial design had no impact on PRO completion rate or baseline scores. Future research should involve analyses by specific cancer types and ideally compare individual data from two similar RCTs (blinded vs. open-label).

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice.

INTRODUCTION: Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance patient-centered care. We evaluated the feasibility of REMOQOL in the French context in the QOLIBRY study. The primary objective was to assess the patients' compliance with REMOQOL. METHODS: The QOLIBRY study was a single-center, prospective study conducted in the University Hospital of Besançon (France). Eligible patients were those treated with systemic therapies for breast, lung or colorectal cancer at any stage. Patients were invited to complete the EORTC QLQ-C30 questionnaire and cancer-site-specific modules before each visit on tablets and/or computers in the hospital or at home. During the consultation, physicians had real-time access to visual summaries of HRQoL scores. Compliance was assessed as adequate if at least 66% of HRQoL assessments were completed during the 4 months of follow-up. RESULTS: Between March 2016 and October 2018, 177 patients were included in the QOLIBRY study. Median age was 64 years (IQR 54-71). The proportion of patients with an adequate compliance rate was 95.5% (n = 63) in the breast cancer cohort, 98.2% (n = 55) in the colorectal cancer cohort, and 90.9% (n = 50) in the lung cancer cohort. The physicians checked the HRQoL results in 73.1% of visits and prescribed supportive care and adapted patient management in 8.3% and 5.2% of visits, respectively. CONCLUSION & PERSPECTIVES: The results of QOLIBRY study suggest that REMOQOL is feasible in the French context. However, information about HRQoL monitoring, training of the physicians in the use of the software, and recommendations for using HRQoL results to guide care are essential and must be improved.

Health-related quality of life assessment for patients with advanced or metastatic renal cell carcinoma treated with a tyrosine kinase inhibitor using electronic patient-reported outcomes in daily clinical practice (QUANARIE trial): study protocol.

BACKGROUND: Two main therapies, pazopanib and sunitinib, are used in the first-line setting for metastatic renal cell carcinoma (mRCC). These two tyrosine kinase inhibitors (TKI) are equally effective in terms of survival; however, they frequently induce adverse events. In this setting, Health-Related Quality of life (HRQoL) is a key element in the choice between these two treatments and the evaluation of treatment effectiveness. It could be of interest to evaluate HRQoL in daily clinical practice to aid adequate therapy choice and management. Currently, the development of information and communication technology may allow HRQoL monitoring in routine practice. The objective of the QUANARIE study is to evaluate the use of HRQoL assessment in daily clinical practice for patients with mRCC treated with TKI using electronic patient-reported outcomes (e-PRO). The present article describes the key elements of the study protocol. METHODS: The QUANARIE study is an interventional, prospective, multicentre trial. Patients diagnosed with mRCC initiating sunitinib or pazopanib treatment will be invited to complete the EORTC QLQ-C30 questionnaire, nine additional questions from the EORTC items library, and the EuroQoL EQ-5D, prior to each visit with the physician. Questionnaires will be completed by patients using tablets and/or computer terminals via the e-PRO software. The physician will have real-time access to a visual summary of the HRQoL evaluation. The primary objective is to assess the proportion of patients having good compliance with Routine Electronic Monitoring of HRQoL (REMOQOL) during the first 12 months. Physicians' satisfaction with REMOQOL will be assessed as a secondary objective. We hypothesise that 80% of patients having good compliance with REMOQOL would be meaningful. A sample size of 56 patients would be needed. DISCUSSION: The results of this study will show whether REMOQOL is feasible on a large scale and whether patients are receptive to this new practice. This study will also determine how real-time multidimensional evaluation of patient perception can help physicians in their daily practice and how they used it in conjunction with other clinical information to manage patient care. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT03062410 ; First Posted: February 23, 2017; Last Update Posted: August 9, 2017.

Development and validation of the FRAGIRE tool for assessment an older person's risk for frailty.

BACKGROUND: Frailty is highly prevalent in elderly people. While significant progress has been made to understand its pathogenesis process, few validated questionnaire exist to assess the multidimensional concept of frailty and to detect people frail or at risk to become frail. The objectives of this study were to construct and validate a new frailty-screening instrument named Frailty Groupe Iso-Ressource Evaluation (FRAGIRE) that accurately predicts the risk for frailty in older adults. METHODS: A prospective multicenter recruitment of the elderly patients was undertaken in France. The subjects were classified into financially-helped group (FH, with financial assistance) and non-financially helped group (NFH, without any financial assistance), considering FH subjects are more frail than the NFH group and thus representing an acceptable surrogate population for frailty. Psychometric properties of the FRAGIRE grid were assessed including discrimination between the FH and NFH groups. Items reduction was made according to statistical analyses and experts' point of view. The association between items response and tests with "help requested status" was assessed in univariate and multivariate unconditional logistic regression analyses and a prognostic score to become frail was finally proposed for each subject. RESULTS: Between May 2013 and July 2013, 385 subjects were included: 338 (88%) in the FH group and 47 (12%) in the NFH group. The initial FRAGIRE grid included 65 items. After conducting the item selection, the final grid of the FRAGIRE was reduced to 19 items. The final grid showed fair discrimination ability to predict frailty (area under the curve (AUC) = 0.85) and good calibration (Hosmer-Lemeshow P-value = 0.580), reflecting a good agreement between the prediction by the final model and actual observation. The Cronbach's alpha for the developed tool scored as high as 0.69 (95% Confidence Interval: 0.64 to 0.74). The final prognostic score was excellent, with an AUC of 0.756. Moreover, it facilitated significant separation of patients into individuals requesting for help from others (P-value < 0.0001), with sensitivity of 81%, specificity of 61%, positive predictive value of 93%, negative predictive value of 34%, and a global predictive value of 78%. CONCLUSIONS: The FRAGIRE seems to have considerable potential as a reliable and effective tool for identifying frail elderly individuals by a public health social worker without medical training.

Quality of Life and Needs in Caregivers: Results From the Prospective Multicentric Open-Label Randomized Study of Informal Caregivers of Elderly Patients.

Objectives: To assess health-related quality of life (QoL) in caregivers of elderly patients with chronic disabilities receiving, or not receiving, social worker support. Methods: This multicenter open-label randomized study assigned caregivers to receive an information booklet, exclusively, or with social worker support. Caregivers completed Short Form-36 (SF-36) and Hospital Anxiety Depression Scale quarterly, and Zarit Burden Interview each semester, for 24 months. We reported caregiver QoL mean changes at 12 and 24 months (M12, M24). Longitudinal QoL analysis up to M24 used mixed models for repeated measures (MMRM). Results: Among the 179 caregivers randomized from 2015 to 2019, the SF-36 physical and mental component summary showed no significant changes at M12 and M24, in terms of neither anxiety nor burden. However, depression significantly increased (M12: 1.4 ± 4.0; M24: 1.7 ± 4.1) with significant adjusted mean increase using MMRM at M24: 3.4 [0.6-2.5] in the control group, exclusively. Conclusion: These findings call for better recognition of the social support to prevent caregiver QoL deterioration and alleviate their depression early in the course of the disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02626377.

Metastatic colorectal carcinoma with signet-ring cells: Clinical, histological and molecular description from an Association des Gastro-Entérologues Oncologues (AGEO) French multicenter retrospective cohort.

BACKGROUND: Metastatic signet-ring cell colorectal carcinoma is rare. We analyzed its clinicopathological and molecular features, prognostic factors and chemosensitivity. METHODS: Retrospective study from 2003 to 2017 in 31 French centers, divided into three groups: curative care (G1), chemotherapy alone (G2), and best supportive care (G3). RESULTS: Tumors were most frequently in the proximal colon (46%), T4 (71%), and poorly differentiated (86%). The predominant metastatic site was peritoneum (69%). Microsatellite instability and BRAF mutation were found in 19% and 9% (mainly right-sided) of patients and RAS mutations in 23%. Median overall survival (mOS) of the patients (n = 204) was 10.1 months (95%CI: 7.9;12.8), 45.1 for G1 (n = 38), 10.9 for G2 (n = 112), and 1.8 months for G3 (n = 54). No difference in mOS was found when comparing tumor locations, percentage of signet-ring cell contingent and microsatellite status. In G1, relapse-free survival was 14 months (95%CI: 6.5-20.9). In G2, median progression-free survival (PFS) was 4.7 months (95%CI: 3.6;5.9]) with first-line treatment. Median PFS was higher with biological agents than without (5.0 vs 3.9 months, p = 0.016). CONCLUSIONS: mSRCC has a poor prognosis with specific location and molecular alterations resulting in low chemosensitivity. Routine microsatellite analysis should be performed because of frequent MSI-high tumors in this population.

Health-related quality of life among long-term survivors of colorectal cancer: a population-based study.

BACKGROUND: The number of long-term colorectal cancer survivors is increasing. Cancer and its treatment can cause physical and psychological complications, but little is known about how it impacts quality of life (QOL) over the long term-5, 10, and 15 years after diagnosis. METHODS: Cancer survivors were randomly selected from three tumor registries in France, diagnosed in 1990 (±1 year), 1995 (±1 year), and 2000 (±1 year). Controls were randomly selected from electoral rolls, stratifying on gender, age group, and residence area. Participants completed two QOL questionnaires, a fatigue questionnaire, an anxiety questionnaire, and a life conditions questionnaire. An analysis of variance was used to compare QOL scores of cancer survivors by period of diagnosis (5, 10, and 15 years) with those of controls, adjusted for sociodemographic data and comorbidities. RESULTS: We included 344 colon cancer and 198 rectal cancer survivors and 1,181 controls. In a global analysis, survivors reported a statistically and clinically significant lower score in social functioning 5 years after diagnosis and higher scores in diarrhea symptoms 5 and 10 years after diagnosis. In subgroup analyses, rectal cancer affected QOL in the physical dimensions at 5 years and in the fatigue dimensions at 5 and 10 years. CONCLUSION: Survivors of colorectal cancer may experience the effects of cancer and its treatment up to 10 years after diagnosis, particularly for rectal cancer. Clinicians, psychologists, and social workers must pay special attention to rectal cancer survivors to improve overall management.

Long-term quality of life after breast cancer: a French registry-based controlled study.

Population-based studies on quality of life (QOL) of long-term breast cancer survivors are quite recent and insufficient attention has been paid to the effect of time since diagnosis. We compared long-term QOL of population-based breast cancer survivors 5, 10, and 15 years after diagnosis with that of healthy controls. Breast cancer survivors were randomly selected from three population-based cancer registries (Bas-Rhin, Calvados and Doubs, France) along with healthy controls, stratified for age and place of residence, randomly selected from electoral rolls. Participants completed five self-administered questionnaires: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Short Form-36 (SF-36), Spielberger State-Trait Anxiety Inventory (STAI), Multidimensional Fatigue Inventory (MFI) and a life conditions questionnaire. An analysis of variance was used to compare QOL scores of breast cancer survivors by period (5, 10, or 15 years) of diagnosis with those of controls, adjusted for sociodemographic data and comorbidities. Six hundred and fifty-two cases and 1,188 controls participated in the study. For many QOL scales, scores were significantly different between cancer survivors and controls. A clinically significant difference was evidenced for the fatigue scales, the SF36 physical functioning, role-physical, and role-emotional scales, with more favorable results for controls. Differences decreased with time and 15-year cancer survivors were generally not different from controls. Scores were particularly influenced by age and mean household income. More efforts should be made, specifically during the first 5 to 10 years after diagnosis, to help women with breast cancer to overcome their impairment in QOL.

Chemotherapy use in end-of-life digestive cancer patients: a retrospective AGEO observational study.

BACKGROUND: The use of chemotherapy (CT) near the end-of-life (EOL) is an important issue in oncology since it could degrade quality of life. CT near EOL is still poorly studied, with no dedicated study in gastrointestinal (GI) cancer patients. AIM: To analyze in GI cancer patients the factors associated with the use of CT within 3- and 1-month before patients' death. METHODS AND PARTICIPANTS: All consecutive patients who died from a GI cancer in 10 French tertiary care hospitals during 2014 were included in this retrospective study. Clinical, demographical and biological data were collected and compared between patients receiving or not CT within 3- and 1-month before death. Variables associated with overall survival (OS) was also determined using of univariate and multivariate analyses with a Cox model. RESULTS: Four hundred and thirty-seven patients with a metastatic GI cancer were included in this study. Among them, 293 pts (67.0%) received CT within 3-months before death, and 121 pts (27.7%) received CT within 1-month before death. Patients receiving CT within 3-months before death were significantly younger (median age: 65.5 vs 72.8 years, p < 0.0001), with a better PS (PS 0 or 1: 53.9 vs 29.3%, p < 0.0001) and a higher albumin level (median: 32.8 vs 31.0 g/L, p = 0.048). Similar results were found for CT within 1 month before death. Palliative care team intervention was less frequent in patients who received CT in their last month of life (39.7% vs 51.3%, p = 0.02). In multivariate analysis, median OS from diagnosis was shorter in the group receiving CT within 1-month before death (HR = 0.59; 95% CI [0.48-0.74]). CONCLUSION: In GI-cancer patients, CT is administered within 3- and 1-month before death, in two and one third of patients, respectively. Patients receiving CT within 1-month before death, had more aggressive disease with poor OS. Palliative care team intervention was associated with less administration of CT in the last month of life. These results highlight the need to better anticipate the time to stop CT treatment in the end-of-life and the importance of an active collaboration between oncology and palliative care teams.

[Attachment and caregivers' life course facing cancer]. / Attachement et parcours de l'aidant face à l'épreuve du cancer.

INTRODUCTION: Since the last cancer plan 2014-2019, the assessment of the impact of the disease on caregivers became essential. The quality of caregiving represents an important part of the patient's quality of life. The main objective was to describe the evolution of caregiver's attachment style during the first three years of the disease support. METHODS: Caregivers have been included through the ICE study (Informal Carers of Elderly). They were taking care for one near parent at least 60 years of age with a diagnosis of cancer (breast, prostate, colorectal). Caregivers were interviewed at home within three months of inclusion in the ICE study. This longitudinal research based on recorded semi-structured interviews and used one scale (RSQ) to evaluate the attachment style: secure attachment, detached-type insecure, preoccupied-type insecure or fearful-type insecure. RESULTS: The evolution of attachment styles reflect different relational strategies among the 33 caregivers included. The three first times of the disease are differently lived by the caregivers and are impacted by an insecurity form. The attachment style is different depending on the stage of the disease and the impact of the assistance provided shows that caregivers use more detachment relational strategy in the first year. Then, between 3 and 15 months, the attachment style is evolving towards more preoccupied style. DISCUSSION: Detached-type insecure caregiver tend to minimize their signs of distress in the first time of disease. By contrast, preoccupied-type insecure adults tend to maximize distress signals. It's important to consider the specificity of each step of the process to better support caregivers.

Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study.

BACKGROUND: A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients. METHODS: Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety. RESULTS: Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively). CONCLUSION: This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.

GINECO Prospective Non-interventional PROSPECTYON Study: Trabectedin Plus Pegylated Liposomal Doxorubicin for Platinum-sensitive Recurrent Ovarian Cancer.

BACKGROUND: Trabectedin and pegylated liposomal doxorubicin (PLD) is an effective combination therapy for platinum-sensitive recurrent ovarian cancer (ROC), particularly for disease relapsing within 6-12 months of platinum therapy. The non-interventional PROSPECTYON study evaluated trabectedin/PLD in French clinical practice. PATIENTS AND METHODS: Patients with ROC after at least one platinum-based regimen received 1.1 mg/m2 trabectedin plus 30 mg/m2 PLD every 3 weeks. Efficacy and safety were evaluated in subgroups according to platinum-free interval [6-12 versus ≥12 months (partially or fully platinum sensitive, respectively)]. RESULTS: Recurrent disease was partially platinum-sensitive in 58 patients and fully sensitive in 33 patients treated between July 2014 and June 2016. Patients in both subgroups received a median of six cycles of trabectedin and PLD. The most common grade 3 or more toxicities were haematological. Median progression-free survival was 6 months for both subgroups. CONCLUSION: Trabectedin/PLD is a valuable treatment option for partially or fully platinum-sensitive ROC.

Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study.

BACKGROUND: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. METHODS: Data from two independent cohorts enrolling patients treated with FFX (n = 107) or GN (n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. RESULTS: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10-21) than in GN groups (9 months; 95% CI: 8-12) before (p = 0.008) and after (p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching (n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX-GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX-GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively (p = 0.094). CONCLUSION: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

Rurality and survival differences in lung cancer: a large population-based multivariate analysis.

Several studies have suggested rural health disadvantages. In France, studies on rural-urban patterns of lung cancer survival have yielded conflicting results. The aim of this analysis was to determine whether rural residence was associated with poor survival in three French counties. The database consisted of all primary lung cancer cases diagnosed in 2000 and 2001 collected through the Doubs cancer registry. A degree of rurality, obtained from socio-demographic and farming parameters of the 1999 French census treated with factor analysis, was attributed to each patient according to his/her place of residence. Among the 802 patients, 21% resided in rural areas, 11% were semi-urban inhabitants and 68% were urban residents. Survival differed significantly between these three rurality categories (p=0.04), with 2-year survival rates of 18, 29 and 24%, respectively. Using a Cox model, rural areas were significantly correlated with poor survival as compared with semi-urban areas (OR=1.42; 95% confidence interval=1.06-1.90; p=0.02). There was no survival difference between semi-urban and urban patients (OR=1.18; 95% confidence interval=0.91-1.53; p=0.21). Patient and tumour characteristics, especially stage and staging procedures, as well as first line treatment, did not vary with the degree of rurality. In conclusion, rurality has to be considered as a strong prognostic factor. Several intricate factors might be hypothesized such as increasing time to diagnosis leading to heavier tumour burden, worse treatment compliance and socioeconomic status. Before practical interventions can be proposed, prospective studies are warranted with further definition of rural risk factors for decreased survival in rural lung cancer patients.

Trastuzumab in Combination with FOLFIRI in Patients with Advanced HER2-Positive Gastro-Esophageal Adenocarcinoma: A Retrospective Multicenter AGEO Study.

BACKGROUND: Trastuzumab with fluoropyrimidine and cisplatin is the standard first-line treatment in patients with HER2-positive advanced gastro-esophageal adenocarcinoma. However, there are no safety and efficacy data of trastuzumab with FOLFIRI. OBJECTIVE: To evaluate safety and efficacy of FOLFIRI plus trastuzumab in patients with HER2-positive advanced gastro-esophageal adenocarcinoma. PATIENTS AND METHODS: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastro-esophageal adenocarcinoma treated with FOLFIRI plus trastuzumab between 2012 and 2015. RESULTS: A total of 33 patients (median age, 60.3; performance status 0-1, 78.8%) with HER2-positive advanced gastro-esophageal adenocarcinoma treated with FOLFIRI plus trastuzumab in first (n = 3), second (n = 20) or third (n = 10) line of chemotherapy were included. There was one case of a severe non-hematological adverse event corresponding to a left ventricular systolic dysfunction. The most common hematological grade 3 or 4 adverse events were neutropenia (12.9%) and thrombocytopenia (6.4%). There was no febrile neutropenia. For patients treated with FOLFIRI plus trastuzumab in second-line chemotherapy, the median overall survival was 9.5 months. CONCLUSIONS: This is the first western population-based study of FOLFIRI plus trastuzumab reporting a satisfactory safety profile and a potential efficacy in advanced HER2-positive gastric cancer.

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: a multicenter AGEO study.

INTRODUCTION: Trastuzumab in combination with platinum-based chemotherapy is the standard first-line regimen in HER2-positive advanced gastric cancer. However, there are very few data concerning efficacy of continuing trastuzumab beyond first-line progression. METHODS: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received a second-line of chemotherapy with or without trastuzumab after progression on platinum-based chemotherapy plus trastuzumab. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method and compared using log-rank test. The prognostic variables with P values ≤ 0.05 in univariate analysis were eligible for the Cox multivariable regression model. RESULTS: From May 2010 to December 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; ECOG performance status [PS] 0-1, 71.2%). The continuation (n=39) versus discontinuation (n=65) of trastuzumab beyond progression was significantly associated with an improvement of median PFS (4.4 versus 2.3 months; P=0.002) and OS (12.6 versus 6.1 months; P=0.001. In the multivariate analysis including the ECOG PS, number of metastatic sites and measurable disease, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.56; 95% CI, 0.35-0.89; P=0.01) and OS (HR, 0.47; 95% CI, 0.28-0.79; P=0.004). CONCLUSION: This study suggests that continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer. These results deserve a prospective randomized validation.

Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: The GERCOR phase II trial ERaFOX.

BACKGROUND: To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer. PATIENTS AND METHODS: Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected. RESULTS: Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding. CONCLUSIONS: Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies.

Efficacy of modern chemotherapy and prognostic factors in patients with ovarian metastases from gastric cancer: A retrospective AGEO multicentre study.

BACKGROUND: Ovarian metastases from gastrointestinal tumours frequently lead to locoregional complications and undermine quality of life. The chemosensitivity of ovarian metastases from gastric cancer is unknown. AIM: To evaluate the efficacy of modern chemotherapy regimens in first-line treatment for patients with ovarian metastases from gastric cancer. METHODS: All consecutive patients with ovarian metastases from gastric cancer who received at least one cycle of chemotherapy were included in this retrospective study. RESULTS: Thirty-five patients were included (median age, 50.5 years; synchronous ovarian metastases, 60%). Seventeen patients (48.6%) underwent oophorectomy. Patients were treated with first-line chemotherapy based on platinum (n=14), irinotecan (n=8), taxane plus platinum (n=4) or epirubicin plus platinum (n=9). The median PFS and OS were 6.8 and 18.8 months, respectively. The objective response rate (ORR) for extra-ovarian (13.6%) and ovarian (20.9%) metastatic sites was not significantly different (p=0.55). There was no significant difference in terms of ORR on ovarian metastatic site according to the first-line chemotherapy (p=0.21). In multivariate analysis, oophorectomy was an independent prognostic factor for OS (p<0.01). CONCLUSIONS: This study suggests that ovarian metastases from gastric cancer are not more resistant than extra-ovarian metastases, and that oophorectomy is an independent prognostic factor significantly linked to OS. Prospective studies are needed to confirm these results.

Evaluation of efficacy and efficiency of a pragmatic intervention by a social worker to support informal caregivers of elderly patients (The ICE Study): study protocol for a randomized controlled trial.

BACKGROUND: Medical progress and the lifestyle modification have prolonged life expectancy, despite the development of chronic diseases. Support and care for older subjects are often provided by a network of informal caregivers composed of family, friends and neighbors, who are essential in helping older persons to continue living at home. It has been shown that the extent and diversity of informal tasks may jeopardize the physical, mental and social wellbeing of caregivers. METHODS/DESIGN: The aim of the Informal Carers of Elderly cohort is to define, through a longitudinal study, profiles of caregivers of older patients with a diagnosis of one of the following diseases: cancer (breast, prostate, colorectal), neurodegenerative diseases (Parkinson's disease, Alzheimer's disease and similar diseases), neurovascular diseases (stroke), sensory diseases (age-related macular degeneration (AMD)) and heart disease (heart failure). Patients must be at least 60 years old and living in the region of Burgundy-Franche-Comte (France). By following the different phases of the caregiving relationship from the announcement of the diagnosis, it will be possible to assess the quality of life of caregivers, coping strategies, levels of anxiety and depression, social support and the extent of their burden. We will also evaluate the efficacy and efficiency of the implementation of a pragmatic intervention by a social worker to help informal caregivers, through a randomized interventional trial nested in the cohort. Qualitative approaches aimed at studying the caregiver/patient relationship, and situations leading to breakdown of the caregiver relationship will be also undertaken. DISCUSSION: Through an analytical and longitudinal definition of profiles of informal caregivers, this study will gather detailed information on their life courses and their health trajectory by identifying consequences associated with the concept of their role as carers. In addition, the randomized interventional trial will explore the relevance of the implementation of a supportive intervention by a social worker to help caregivers. These data will help to identify strategies that could be used to improve the existing sources of aid and to propose new approaches to help caregivers. This study will provide the opportunity to identify the most relevant means of support adapted to caregivers, and provide an impulse for new health care policies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02626377 . Retrospectively registered on 9 December 2015. Protocol date/version: 23 October 2014/version 2.