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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 + nab-paclitaxel (13%) in the first line. Median OS for first-line FOLFIRINOX, gemcitabine + nab-paclitaxel, and gemcitabine monotherapy was 6.6, 4.7, and 2.9 months, respectively. Compared to FOLFIRINOX, gemcitabine + 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 + 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.

Background: Maintaining a sufficient health-related quality of life (HRQoL) is important in the palliative treatment of patients with metastatic colorectal cancer (mCRC). The ORCHESTRA trial (ClinicalTrials.gov identifier: NCT01792934) is designed to prospectively evaluate overall survival benefit and impact on HRQoL of tumor debulking when added to first-line palliative systemic therapy in patients with multiorgan mCRC. In the present study, we report the HRQoL associated with this combination treatment compared with standard systemic therapy. Methods: Patients included in the ORCHESTRA trial with clinical benefit after 3 or 4 cycles of first-line palliative systemic therapy with fluoropyrimidines and oxaliplatin with or without bevacizumab were randomly assigned to maximal tumor debulking followed by systemic therapy versus systemic therapy alone. Patients completed the EORTC Quality of Life Questionnaire-Core 30 and the Multidimensional Fatigue Inventory questionnaire at prespecified time points during treatment. Between-group differences in HRQoL over time were evaluated with linear mixed model analyses. A pattern mixture approach was applied to correct for missing questionnaires due to progressive disease. Results: A total of 300 patients were randomized to the intervention arm (n=148) or the standard arm (n=152). No statistically significant or clinically relevant differences in HRQoL and fatigue were observed when tumor debulking was added to systemic therapy. In patients of both study arms, HRQoL after 1 year of treatment was not significantly different from HRQoL at the time of randomization. Patients in the intervention arm experienced serious adverse events (SAEs) twice as often as patients in the standard arm (P≤.001). Conclusions: Maximal tumor debulking in combination with palliative systemic therapy in patients with multiorgan mCRC was significantly associated with more SAEs resulting from local therapy but no difference in HRQoL compared with palliative systemic therapy alone. There is a remarkable lack of association between the occurrence of SAEs and impact on HRQoL.

Background: A relationship between quality of life (QoL) and survival has been shown for several types of cancer, mostly in clinical trials with highly selected patient groups. The relationship between QoL and survival for patients with pancreatic or periampullary cancer is unclear. Methods: This study analyzed QoL data from a prospective multicenter patient-reported outcome registry in patients with pancreatic or periampullary carcinoma registered in the nationwide Netherlands Cancer Registry (2015–2018). Baseline and delta QoL, between baseline and 3-month follow-up, were assessed with the Happiness, EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30), and QLQ-PAN26 questionnaires. The relationship between QoL and survival was assessed using Cox regression models, and additional prognostic value of separate items was assessed using Nagelkerke R² (explained variance). Results: For the baseline and delta analyses, 233 and 148 patients were available, respectively. Most were diagnosed with pancreatic adenocarcinoma (n=194; 83.3%) and had stage III disease (n=77; 33.0%), with a median overall survival of 13.6 months. Multivariate analysis using baseline scores indicated several scales to be of prognostic value for the total cohort (ie, happiness today, role functioning, diarrhea, pancreatic pain, and body image; hazard ratios all P<.05) and for patients without resection (ie, overall satisfaction with life, physical and cognitive functioning, QLQ-C30 summary score, fatigue, pain, constipation, diarrhea, and body image; hazard ratios all P<.05). Except for diarrhea, all QoL items accounted for >5% of the additional explained variance and were of added prognostic value. Multivariate analysis using delta QoL revealed that only constipation was of prognostic value for the total cohort, whereas no association with survival was found for subgroups with or without resection. Conclusions: In a multicenter cohort of patients with pancreatic or periampullary carcinoma, QoL scores predicted survival regardless of patient, tumor, and treatment characteristics. QoL scores may thus be used for shared decision-making regarding disease management and treatment choice.