Real-world evidence of adjuvant gemcitabine plus capecitabine vs gemcitabine monotherapy for pancreatic ductal adenocarcinoma

The added value of capecitabine to adjuvant gemcitabine monotherapy (GEM) in pancreatic ductal adenocarcinoma (PDAC) was shown by the ESPAC-4 trial. Real-world data on the effectiveness of gemcitabine plus capecitabine (GEMCAP), in patients ineligible for mFOLFIRINOX, are lacking. Our study assessed whether adjuvant GEMCAP is superior to GEM in a nationwide cohort. Patients treated with adjuvant GEMCAP or GEM after resection of PDAC without preoperative treatment were identified from The Netherlands Cancer Registry (2015-2019). The primary outcome was overall survival (OS), measured from start of chemotherapy. The treatment effect of GEMCAP vs GEM was adjusted for sex, age, performance status, tumor size, lymph node involvement, resection margin and tumor differentiation in a multivariable Cox regression analysis. Secondary outcome was the percentage of patients who completed the planned six adjuvant treatment cycles. Overall, 778 patients were included, of whom 21.1% received GEMCAP and 78.9% received GEM. The median OS was 31.4 months (95% CI 26.8-40.7) for GEMCAP and 22.1 months (95% CI 20.6-25.0) for GEM (HR: 0.71, 95% CI 0.56-0.90; logrank P =.004). After adjustment for prognostic factors, survival remained superior for patients treated with GEMCAP (HR: 0.73, 95% CI 0.57-0.92, logrank P =.009). Survival with GEMCAP was superior to GEM in most subgroups of prognostic factors. Adjuvant chemotherapy was completed in 69.5% of the patients treated with GEMCAP and 62.7% with GEM (P =.11). In this nationwide cohort of patients with PDAC, adjuvant GEMCAP was associated with superior survival as compared to GEM monotherapy and number of cycles was similar

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

The fear of cancer recurrence and progression in patients with pancreatic cancer

Purpose: It is plausible that patients with pancreatic cancer experience fear of tumor recurrence or progression (FOP). The aim of this study was to compare FOP in patients with pancreatic cancer treated with surgical resection, palliative systemic treatment, or best supportive care (BSC) and analyze the association between quality of life (QoL) and FOP and the effect of FOP on overall survival (OS). Methods: This study included patients diagnosed with pancreatic cancer between 2015 and 2018, who participated in the Dutch Pancreatic Cancer Project (PACAP). The association between QoL and WOPS was assessed with logistic regression analyses. OS was evaluated using Kaplan–Meier curves with the log-rank tests and multivariable Cox proportional hazard analyses adjusted for clinical covariates and QoL. Results: Of 315 included patients, 111 patients underwent surgical resection, 138 received palliative systemic treatment, and 66 received BSC. Patients who underwent surgical resection had significantly lower WOPS scores (i.e., less FOP) at initial diagnosis compared to patients who received palliative systemic treatment or BSC only (P < 0.001). Better QoL was independently associated with the probability of having a low FOP in the BSC (OR 0.95, 95% CI 0.91–0.98) but not in the surgical resection (OR 0.97, 95% CI 0.94–1.01) and palliative systemic treatment groups (OR 0.97, 95% CI 0.94–1.00). The baseline WOPS score was not independently associated with OS in any of the subgroups. Conclusion: Given the distress that FOP evokes, FOP should be explicitly addressed by health care providers when guiding pancreatic cancer patients through their treatment trajectory, especially those receiving palliative treatment or BSC

Heterogeneity of first-line palliative systemic treatment in synchronous metastatic esophagogastric cancer patients : a real-world evidence study

The optimal first-line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real-world use of first-line systemic treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first-line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010–2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab-containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab-containing regimen. The highest median OS was found in patients receiving a trastuzumab-containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83–1.02; TTF: HR 0.92, 95%CI 0.82–1.04) but significantly more grade 3–5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first-line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets

Heterogeneity of first-line palliative systemic treatment in synchronous metastatic esophagogastric cancer patients: A real-world evidence study

The optimal first-line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real-world use of first-line systemic treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first-line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010–2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab-containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab-containing regimen. The highest median OS was found in patients receiving a trastuzumab-containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83–1.02; TTF: HR 0.92, 95%CI 0.82–1.04) but significantly more grade 3–5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first-line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets

Hospital volume and beyond first-line palliative systemic treatment in metastatic oesophagogastric adenocarcinoma: A population-based study

Background: Beyond first-line palliative systemic treatment can be beneficial to selected oesophagogastric cancer patients, but experience with its administration may be limited and vary among hospitals. In a population-based study, we analysed the association between hospital systemic treatment volume and administration of beyond first-line treatment in oesophagogastric adenocarcinoma, as well as the effect on overall survival (OS). Methods: Synchronous metastatic oesophagogastric adenocarcinoma patients (2010-2017) were selected from the Netherlands Cancer Registry. Hospitals were categorised in volumes quartiles. The association between hospital systemic treatment volume and the use of beyond first-line treatment was assessed using trend and multivariable logistic regression analyses. OS was compared between hospitals with high and low beyond first-line treatment administration and treatment strategies using Kaplan-Meier curves with log-rank test and multivariable Cox proportional hazard regression. Results: Beyond first-line treatment was administered in 606 of 2,466 patients who received first-line treatment, and increased from 20% to 31% between 2010 and 2017 (P <0.001). The lowest hospital volumes were independently associated with lower beyond first-line treatment administration compared to the highest volume (OR 0.62, 95% CI 0.39-0.99; OR 0.67, 95% CI 0.48-0.95). Median OS was higher in all patients treated in hospitals with a high versus low beyond first-line treatment administration (7.9 versus 6.2 months, P <0.001). Second-line paclitaxel/ramucirumab was administered most frequently and independently associated with longer OS compared to taxane monotherapy (HR 0.74, 95% CI 0.59-0.92). Conclusion: Higher hospital volume was associated with increased beyond first-line treatment administration in oesophagogastric adenocarcinoma. Second-line paclitaxel/ramucirumab resulted in longer survival compared to taxane monotherapy. (C) 2020 The Authors. Published by Elsevier Ltd

First- and Second-Line Palliative Systemic Treatment Outcomes in a Real-World Metastatic Pancreatic Cancer Cohort

Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor survival rate, which can be improved by systemic treatment. Consensus on the most optimal first- and second-line palliative systemic treatment is lacking. The aim of this study was to describe the use of first- and second-line systemic treatment, overall survival (OS), and time to failure (TTF) of first- and second-line treatment in metastatic PDAC in a real-world setting. Patients and Methods: Patients with synchronous metastatic PDAC diagnosed between 2015 and 2018 who received systemic treatment were selected from the nationwide Netherlands Cancer Registry. OS and TTF were evaluated using Kaplan-Meier curves with log-rank test and multivariable Cox proportional hazard analyses. Results: The majority of 1,586 included patients received FOLFIRINOX (65%), followed by gemcitabine (18%), and gemcitabine 1 nabpaclitaxel (13%) in the first line. Median OS for first-line FOLFIRINOX, gemcitabine 1 nab-paclitaxel, and gemcitabine monotherapy was 6.6, 4.7, and 2.9 months, respectively. Compared to FOLFIRINOX, gemcitabine 1 nab-paclitaxel showed significantly inferior OS after adjustment for confounders (hazard ratio [HR], 1.20; 95% CI, 1.02-1.41), and gemcitabine monotherapy was independently associated with a shorter OS and TTF (HR, 1.98; 95% CI, 1.71-2.30 and HR, 2.31; 95% CI, 1.88-2.83, respectively). Of the 121 patients who received second-line systemic treatment, 33% received gemcitabine 1 nab-paclitaxel, followed by gemcitabine (31%) and FOLFIRINOX (10%). Conclusions: Based on population-based data in patients with metastatic PDAC, treatment predominantly consists of FOLFIRINOX in the first line and gemcitabine with or without nab-paclitaxel in the second line. FOLFIRINOX in the first line shows superior OS compared with gemcitabine with or without nab-paclitaxel

Hospital volume and beyond first-line palliative systemic treatment in metastatic oesophagogastric adenocarcinoma:A population-based study

Background: Beyond first-line palliative systemic treatment can be beneficial to selected oesophagogastric cancer patients, but experience with its administration may be limited and vary among hospitals. In a population-based study, we analysed the association between hospital systemic treatment volume and administration of beyond first-line treatment in oesophagogastric adenocarcinoma, as well as the effect on overall survival (OS).Methods: Synchronous metastatic oesophagogastric adenocarcinoma patients (2010-2017) were selected from the Netherlands Cancer Registry. Hospitals were categorised in volumes quartiles. The association between hospital systemic treatment volume and the use of beyond first-line treatment was assessed using trend and multivariable logistic regression analyses. OS was compared between hospitals with high and low beyond first-line treatment administration and treatment strategies using Kaplan-Meier curves with log-rank test and multivariable Cox proportional hazard regression.Results: Beyond first-line treatment was administered in 606 of 2,466 patients who received first-line treatment, and increased from 20% to 31% between 2010 and 2017 (P &lt;0.001). The lowest hospital volumes were independently associated with lower beyond first-line treatment administration compared to the highest volume (OR 0.62, 95% CI 0.39-0.99; OR 0.67, 95% CI 0.48-0.95). Median OS was higher in all patients treated in hospitals with a high versus low beyond first-line treatment administration (7.9 versus 6.2 months, P &lt;0.001). Second-line paclitaxel/ramucirumab was administered most frequently and independently associated with longer OS compared to taxane monotherapy (HR 0.74, 95% CI 0.59-0.92).Conclusion: Higher hospital volume was associated with increased beyond first-line treatment administration in oesophagogastric adenocarcinoma. Second-line paclitaxel/ramucirumab resulted in longer survival compared to taxane monotherapy. (C) 2020 The Authors. Published by Elsevier Ltd.</p

Increased assessment of HER2 in metastatic gastroesophageal cancer patients:a nationwide population-based cohort study

Background: Addition of trastuzumab to first-line palliative chemotherapy in gastroesophageal cancer patients with HER2 overexpression has shown to improve survival. Real-world data on HER2 assessment and administration of trastuzumab are lacking. The aim of this study was to assess HER2 testing, trastuzumab administration, and overall survival (OS) in a nationwide cohort of metastatic gastroesophageal cancer patients. Methods: Data of patients with synchronous metastatic gastroesophageal adenocarcinoma diagnosed in 2010–2016 that received palliative systemic treatment (n = 2846) were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. The ToGA trial criteria were used to determine HER2 overexpression. Proportions of HER2 tested patients were analyzed between hospital volume categories using Chi-square tests, and over time using trend analysis. OS was tested using the Kaplan Meier method with log rank test. Results: HER2 assessment increased annually, from 18% in 2010 to 88% in 2016 (P < 0.01). Median OS increased from 6.9 (2010–2013) to 7.9 months (2014–2016; P < 0.05). Between the hospitals, the proportion of tested patients varied between 29–100%, and was higher in high-volume hospitals (P < 0.01). Overall, 77% of the HER2 positive patients received trastuzumab. Median OS was higher in patients with positive (8.8 months) and negative (7.4 months) HER2 status, compared to non-tested patients (5.6 months; P < 0.05). Conclusion: Increased determination of HER2 and administration of trastuzumab have changed daily practice management of metastatic gastroesophageal cancer patients receiving palliative systemic therapy, and possibly contributed to their improved survival. Further increase in awareness of HER2 testing and trastuzumab administration may improve quality of care and patient outcomes