Search

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. [ABSTRACT FROM AUTHOR]

Background: In 2-5% of patients with colorectal cancer (CRC), human epidermal growth factor 2 (HER2) is amplified or overexpressed. Despite prior evidence that anti-HER2 therapy confers clinical benefit (CB) in one-third of these patients, it is not approved for this indication in Europe. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile. Here, we present the results of the cohort 'trastuzumab/pertuzumab for treatment-refractory patients with RAS/BRAF-wild-type HER2amplified metastatic CRC (HER2+mCRC)'., Methods: Patients with progressive treatment-refractory RAS/BRAF-wild-type HER2+mCRC with measurable disease were included for trastuzumab plus pertuzumab treatment. Primary endpoints of DRUP are CB (defined as confirmed objective response (OR) or stable disease (SD) ≥ 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and 24 patients in stage 2 if at least 1/8 patients had CB. To identify biomarkers for response, whole genome sequencing (WGS) was performed on pre-treatment biopsies., Results: CB was observed in 11/24 evaluable patients (46%) with HER2+mCRC, seven patients achieved an OR (29%). Median duration of response was 8.4 months. Patients had undergone a median of 3 prior treatment lines. Median progression-free survival and overall survival were 4.3 months (95% CI 1.9-10.3) and 8.2 months (95% CI 7.2-14.7), respectively. No unexpected toxicities were observed. WGS provided potential explanations for resistance in 3/10 patients without CB, for whom WGS was available., Conclusions: The results of this study confirm a clinically significant benefit of trastuzumab plus pertuzumab treatment in patients with HER2+mCRC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Derk-Jan A. de Groot received funding for research grants from Siemens and Hoffman-La Roche. All outside the submitted work and all money had been received by the UMCG. Jeanine M.L. Roodhardt is a member of Advisory boards from Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, GSK and Amgen (all paid to institution), received research funding from BMS, Pierre Fabre, Servier, Cleara, Xilis, DoMore diagnostics and HUB organoids B.V. (all paid to institution) and is a Board Member of Foundation Hubrecht Oragnoid Biobank. Liselot Valkenburg-van Iersel reported consulting fees from Sevier, Amgen and Pierre Fabre. Emile E. Voest is founder and current member of the supervisory board of the Hartwig Medical Foundation, independent non-executive director of Sanofi, co-founder of Mosaic Therapeutics, and a board member and founder of the Center for Personalized Cancer Treatment. He has received clinical study grants from Amgen, AstraZenica, BI, BMS, Clovis, Eli Lilly, GSK, Ipsen, MSD, Novartis, Pfizer, Roche and Sanofi, all paid to the Netherlands Cancer Institute. The other authors declare no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care., Methods: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017-2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan-Meier and Log-rank tests., Results: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017-2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017-2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065)., Conclusion: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer., Competing Interests: Conflict of interest JdV has served as a consultant for Amgen, AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier. All outside the submitted work. The other authors have no conflicts., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin., Methods: Patients diagnosed with non-metastatic periampullary cancer in 2012-2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan-Meier analysis and multivariable Cox regression analyses, stratified by origin., Results: Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55-0.69) and DC (HR = 0.69; 95% CI 0.48-0.98), but not AC (HR = 0.87; 95% CI 0.62-1.22) and DA (HR = 0.85; 95% CI 0.48-1.50)., Conclusion: This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Ampullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016., Methods: Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease., Results: In total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989-1995 to 0.68 per 100,000in 2010-2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989-1995 to 63.9% in 2010-2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9-22.8) in 1989-1995 to 29.1% (26.0-31.2) in 2010-2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6-5.0) to 5.9 months (4.7-7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients., Conclusion: Both incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy., Competing Interests: Declaration of competing interest Drs. de Vos-Geelen reports grants, personal fees and non-financial support from Servier, personal fees from AstraZeneca, personal fees from MSD, personal fees from Pierre Fabre, personal fees from Amgen, outside the submitted work. Dr. ir. Geurts reports grants from Roche, grants from Pfizer, grants from Novartis, grants from Eisai, grants from Lilly, outside the submitted work. Dr. Haj Mohammad reports non-financial support from Servier, non-financial support from MSD, non-financial support from BMS, non-financial support from Eli Lily, non-financial support from Astra Zeneca, outside the submitted work. Dr. van Laarhoven reports grants and non-financial support from BMS, grants and non-financial support from Celgene, grants and non-financial support from Lilly, grants and non-financial support from Nordic, grants and non-financial support from Servier, grants from Bayer, grants from Merck Serono, grants from MSD, grants from Philips, outside the submitted work. Dr. Tjan-Heijnen reports grants and personal fees from Roche, grants and personal fees from Novartis, grants and personal fees from Pfizer, grants and personal fees from Lilly, personal fees from Accord Healthcare, grants from AstraZeneca, grants from Eisai, grants from Daiichi Sankyo, outside the submitted work. Dr. Valkenburg-van Iersel reports non-financial support from Servier, non-financial support from Pierre Fabre, non-financial support from Roche, outside the submitted work. Dr. Wilmink reports grants and non-financial support from Servier, non-financial support from MSD, non-financial support from AstraZeneca, grants and non-financial support from Celgene, grants from Halozyme, grants from Merck, grants from Roche, grants from Pfizer, grants from Amgen, grants from Novartis, outside the submitted work. The other authors have declared no conflicts of interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A bioanalytical assay for the new poly(ADP-ribose) polymerase-1 inhibitor olaparib in combination with melphalan was developed and validated. For the quantitative assay, human plasma samples were pre-treated on ice using protein precipitation with 2% (v/v) acetic acid in acetonitrile containing erlotinib and melphalan-d₈ as internal standards. The extract was diluted with water and injected into the chromatographic system. This system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with an isocratic elution using 0.01% (v/v) of formic acid in a mixture of water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10-5000 ng/ml calibration range for both drugs. The lowest level of this range corresponded to the lower limit of quantification. Within day precisions were 3.0-9.3%, between day precisions 6.0-9.8% and accuracies were between 101 and 110% for the whole calibration range. After validation the assay was used to assess the pharmacokinetics of olaparib in a patient with metastatic breast carcinoma. In addition, systemic exposure of melphalan was monitored in patients subjected to isolated hepatic perfusion with this drug. Both applications show that the new assay can be applied for human pharmacokinetic studies for both drugs., (Copyright © 2011 Elsevier B.V. All rights reserved.)