Virtual Library
Start Your Search
J.G. Aerts
Author of
-
+
ISS04 - Industry Supported Symposium: Treatment Selection Strategies in Advanced NSCLC - A Symphony of Views - Eli Lilly and Company (ID 438)
- Event: WCLC 2016
- Type: Industry Supported Symposium
- Track:
- Presentations: 1
- Moderators:G.V. Scagliotti, T. Mok
- Coordinates: 12/04/2016, 17:15 - 18:45, Hall C1
-
+
ISS04.02 - Orchestral Manoeuvres of the Immuno Checkpoints: Targeted or Untargeted Agents? (ID 6854)
17:20 - 17:45 | Author(s): J.G. Aerts
- Abstract
Abstract not provided
-
+
OA13 - Immunotherapy in Malignant Pleural Mesothelioma: Current Status of Trials and New Approaches (ID 392)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
-
+
OA13.06 - Autologous Dendritic Cells Loaded with Allogeneic Tumor Cell Lysate (Pheralys®) in Patients with Mesothelioma: Final Results of a Phase I Study (ID 5631)
15:15 - 15:25 | Author(s): J.G. Aerts
- Abstract
- Presentation
Background:
Mesothelioma is an aggressive malignancy without curative treatment options. We have previously shown promising activity of dendritic cell (DC) immunotherapy loaded with autologous tumor cell lysate (Hegmans 2013, Cornelissen 2016). Because of quality and quantity issues (availability, standardization etc) with the autologous lysate, we have developed an off-the-shelf allogenic tumor cell lysate from human mesothelioma cell lines (Pheralys.[®]).
Methods:
Patients (pts) with advanced mesothelioma, either treatment naive, or non-progressing after chemotherapy, were included. Leucapheresis was performed to obtain an enriched monocyte fraction from which immature DC were generated which were loaded with the allogenic lysate. The DC were matured, frozen and stored. In subsequent cohorts of 3 pts 10, 25, or 50 × 10[6 ]DC were administered IV and intradermally, 3 times at a bi-weekly interval and after 3 and 6 months. Primary endpoint was toxicity occurring within 8 weeks after the first vaccination. Secondary endpoints were response rate (RR), progression free survival (PFS) and overall survival (OS). PFS and OS were determined from time of registration in the trial. Immunological read-outs were performed (DTH skin testing, peripheral blood testing).
Results:
Nine pts (median age 69yrs, 8 male, 1 female) were included. All patients developed transient grade 1-fever and a grade 1-2 injection site reaction. No dose limiting toxicities or autoimmunity signs were observed. In 2 pts (22%), both treated with 25 ×10[6] cells, a partial response (PR) was observed, the other 7 pts had stable disease as best overall response. All patients are alive with a median follow up of 11.9 months after trial inclusion(range 7.6-16.5 months). Median PFS was 8.3 months (95% confidence interval (CI) 3.7-not yet reached), PFS at 12 months was 33% (95% CI 8%-62%). Data on immunological read outs are pending.
Conclusion:
DC immunotherapy with allogenic tumor cell lysate is safe and clinically active. Data on PFS and OS are promising and still maturing. The recommended dose for future studies will be 25 * 10[6] cells based on the responses and logistic reasons (the number of monocytes obtained during leucapheresis to generate 5 vaccinations). A randomized trial comparing DC therapy with Pheralys versus best supportive care as maintenance treatment after chemotherapy is planned to start in Q1 2017.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P1.06-014 - What Factors Determine Treatment Satisfaction in Patients with Advanced NSCLC Receiving Chemotherapy? (ID 6025)
14:30 - 14:30 | Author(s): J.G. Aerts
- Abstract
Background:
In advanced non-small cell lung cancer (NSCLC) treatment decisions regarding palliative chemotherapy are complex due to limited survival gain and treatment-related toxicities. Insight into determinants of patients’ treatment satisfaction may impact decision-making and patient care. We determined the relation of patient- and treatment-related variables to treatment satisfaction.
Methods:
In a prospective observational multi-center study, patients with stage IIIB or IV NSCLC receiving pemetrexed (PEM)-based chemotherapy as first- or second-line treatment were enrolled. After four cycles of chemotherapy, patients completed the WHO Quality of Life-BREF (WHOQoL-BREF), which contains one item measuring overall QoL on a 1-5 scale, and the Cancer Therapy Satisfaction Questionnaire (CTSQ). The CTSQ was recently validated (Cheung et al, Qual Life Res. 2016;25(1):71-80). It consists of 16 items scored on a 1-5 scale and contains three domains. Only satisfaction with therapy (SWT) and feelings about side effects (FSE) were used. The domain scores range between 0-100, with higher scores representing better SWT and more positive FSE. We collected sociodemographic information and ECOG performance status at baseline. Adverse events (cancer- or therapy-related) during treatment were weekly registered (CTCAE 3.0). Tumor response measurements were obtained (RECIST 1.1). Patient- and treatment-related determinants univariably associated with SWT (p<0.05) were analyzed using multivariable linear regression (method: Enter).
Results:
Of the 95 patients receiving four cycles of chemotherapy, 69 patients completed the CTSQ. The majority of these patients had stage IV NSCLC (87.7%) and received PEM-based therapy as first-line treatment (92.3%). Treatment resulted in stable disease (SD; 53.8%), partial response (PR; 40.0%) and progressive disease (PD; 6.2%). The mean SWT domain score was 79.6±13.1. Univariably, higher patients’ age (p=0.034), tumor response (PR vs. SD or PD, p=0.040), overall QoL (p=0.008) and FSE (p=0.004) were significantly related to SWT. The frequency of (severe) adverse events was not associated with SWT (p=0.546). After including these variables in the multivariable analysis, only age (β=0.44; 95%CI (0.09-0.79)) and FSE (β=0.13; 95%CI (0.00-0.26) were independently related to SWT.
Conclusion:
Importantly, higher SWT in elderly supports the opinion that palliative chemotherapy should not be reserved for younger age groups. Although symptomatic adverse events are known key contributors to QoL, the frequency of (severe) adverse events was not related with SWT. However, in patients with better FSE treatment satisfaction was higher. Therefore, patients’ education about and management of adverse events may have added value in maintaining patients’ well-being during chemotherapy, ultimately resulting in higher treatment satisfaction. This study is funded by ZonMw, the Netherlands.
-
+
P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03a-011 - Population Pharmacokinetic/Pharmacodynamic Monitoring of Pemetrexed to Predict Survival in Patients with Advanced NSCLC (ID 6226)
14:30 - 14:30 | Author(s): J.G. Aerts
- Abstract
Background:
A major challenge in advanced non-small cell lung cancer (NSCLC) remains the identification of predictors of clinical benefit from pemetrexed. Total systemic exposure to pemetrexed and its metabolites could be predictive for progression-free and overall survival (PFS/OS). However, sampling times in population pharmacokinetic (PK) analyses of pemetrexed are limited. We performed population PK modeling of pemetrexed during total treatment period and evaluated total systemic exposure as a predictor.
Methods:
In a prospective observational multi-center study, treatment-naive patients with stage IIIB or IV NSCLC receiving pemetrexed/platinum treatment were enrolled. Pemetrexed, dosed based on body surface area (500mg/m[2]), was administered as a 10-minute intravenous infusion every 21 days. Prior to and weekly after each pemetrexed administration, plasma sampling was performed (cycle-PK). Simultaneously, glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboriation (CKD-EPI) formula. In a subgroup, blood samples were collected at 10, 30 minutes and 1,2,4, 8, 24 hours after start of pemetrexed infusion (24-hour-PK). We used a recently validated assay to quantify plasma pemetrexed concentrations (Stoop et al, J Pharm Biomed Anal 2016;128:1-8). Population PK analyses were performed using nonlinear mixed effects modeling (NONMEM version 7.2). The final model, based on both cycle-PK and 24-hour-PK, was used to estimate the area under the plasma concentration versus time curve during cycle 1 (AUC~cycle~). With a Cox-regression analysis we examined the relation between AUC~cycle~ and OS/PFS, adjusted for known prognostic factors (sex, disease stage, WHO performance-score).
Results:
For 97 of the 151 patients, concentrations of pemetrexed were quantified (24-hour-PK, n=15; cycle-PK, n=82). A two-compartment model parametrized (population estimate (%standard error of the estimate) in terms of clearance (CL; 5.44L/h (14.9%)), central distribution volume (V~1~; 19.6L (11.3%)), peripheral distribution volume (V~2~; 173L (32.7%)), intercompartimental clearance (Q; 0.19L/h (31.6%)) and incorporated between-patient variability of CL (10.7%), estimated cycle-PK appropriately. GFR and other covariates did not improve the estimation of the parameters. The AUC~cylce ~was significantly different between males (190.8±64.9mg·h/L) and females (165.4±47.2mg·h/L). When we stratified for sex, the highest quartile of AUC independently predicted worse OS (HR=3.06, 95%CI: 1.43-6.57) and PFS (HR=2.79 95%CI: 1.36-5.70), adjusted for the remaining prognostic factors, GFR and pemetrexed dosage.
Conclusion:
Paradoxically worse OS and PFS in patients with high plasma pemetrexed AUC may suggest lower intracellular levels of pemetrexed. Another possibility is that these patients poorly metabolize pemetrexed into its more effective metabolites, which inhibit tumor growth more strongly by prolonged intracellular retention and higher affinity to target enzymes.
-
+
P2.03a-012 - Nephrotoxicity in Patients with Advanced NSCLC Receiving Pemetrexed-Based Chemotherapy (ID 6028)
14:30 - 14:30 | Author(s): J.G. Aerts
- Abstract
Background:
In patients with advanced non-small cell lung cancer (NSCLC) pemetrexed (PEM) is increasingly used as maintenance therapy after induction PEM/platinum treatment. Despite the extensive use of PEM, the incidence of nephrotoxicity during (maintenance) PEM therapy has not been systematically evaluated. Knowledge about nephrotoxicity during PEM-based treatment could determine the need for adapted renal protective strategies. We assessed the occurrence of nephrotoxicity and its influence on treatment continuation in NSCLC patients receiving PEM-based therapy.
Methods:
In a prospective observational multi-center study, treatment-naive patients with stage IIIB or IV NSCLC were enrolled. Patients were treated with PEM-cisplatin (PEMCIS; PEM 500mg/m[2] and CIS 75mg/m[2]) or PEM-carboplatin (PEMCAR; CAR AUC=5). Patients with at least disease stabilization after four cycles and a favorable toxicity profile were eligible for PEM maintenance therapy. Prior to the initial PEM/platinum cycle, baseline serum creatinine (μmol/l) was obtained. Subsequently, prior to and weekly after each administration of PEM(/platinum) serum creatinine was measured. Glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboriation (CKD-EPI) formula. Acute kidney disease (AKD) was defined as >1.5-fold increase of serum creatinine and/or decrease in GFR >35% or GFR<60mL/min within 3 months (KDIGO).
Results:
Of the 151 patients starting PEM-based therapy, the majority of patients had stage IV disease (86.8%) and they were treated with PEMCIS (64.2%) or PEMCAR (35.8%). During the first four cycles, treatment was discontinued in four patients (2.6%) due to AKD. Patients starting maintenance therapy (n=44, 29.1%) received a median number of 4 PEM cycles. During maintenance treatment with PEM, 12 patients developed AKD (27.3%): three patients could continue treatment after recovery of renal function and in one patient AKD was a part of septic shock. The remaining eight patients (18.2%) stopped treatment due to renal impairment. From patients with a decreased renal function at baseline (eGFR<90mL/min) a significantly higher proportion of patients stopped maintenance therapy due to renal impairment compared to patients with an eGFR≥90mL/min at baseline (6/11 vs. 2/33, p<0.05).
Conclusion:
Patients have a significant risk of developing nephrotoxicity leading to treatment discontinuation during maintenance therapy, especially if the renal clearance is impaired at the start of induction PEM/platinum therapy. In those patients a cumulative systemic dose of PEM or increased susceptibility may play a role in the development of nephrotoxicity. Patients might benefit from altered renal protective strategies, like continuation of hydration during maintenance therapy or dose-adjustment based on renal function. This study was funded by ZonMw, the Netherlands.
