scholarly journals Efficacy and Safety of Tumor Treating Fields (TTFields) in Elderly Patients with Newly Diagnosed Glioblastoma: Subgroup Analysis of the Phase 3 EF-14 Clinical Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Zvi Ram ◽  
Chae-Yong Kim ◽  
Andreas F. Hottinger ◽  
Ahmed Idbaih ◽  
Garth Nicholas ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Elderly Patients ◽  
Subgroup Analysis ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Skin Reactions ◽  
Tumor Treating Fields ◽  
Grade 3

BackgroundUnderstudied elderly patients comprise a large segment of high-risk patients with glioblastoma (GBM) that are challenging to treat. Tumor Treating Fields (TTFields) is a locoregional, noninvasive, antimitotic therapy delivering low-intensity, intermediate-frequency alternating electric fields to the tumor. In the phase 3 EF-14 clinical trial, TTFields (200 kHz) improved median progression-free survival (PFS) and median overall survival (OS) in patients with newly diagnosed GBM (ndGBM) when added concomitantly to maintenance temozolomide (TMZ). This EF-14 subgroup analysis evaluated the safety and efficacy of TTFields in elderly patients.MethodsAll 134 patients who are ≥65 years of age were included (TTFields/TMZ combination, n=89; TMZ monotherapy, n=45; 2:1 ratio of randomization). PFS and OS were analyzed using Kaplan–Meier methodology (α=0.05). Health-related quality-of-life (HRQoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire QLQ-C30 supplemented with the brain tumor module (QLQ-BN20). Adverse events (AEs) were evaluated using Common Terminology Criteria for AEs (CTCAE) v4.0.ResultsThe PFS was 6.5 months in patients randomized to the treatment group with TTFields/TMZ combination versus 3.9 months in patients treated with TMZ monotherapy (HR, 0.47; 95% CI, 0.30–0.74; P<0.0236). The OS was 17.4 months in patients treated with TTFields/TMZ combination versus 13.7 months in patients treated with TMZ monotherapy (HR, 0.51; 95% CI, 0.33–0.77; P<0.0204). Annual survival rates with TTFields/TMZ versus TMZ monotherapy were 39% (95% CI, 29–50%) versus 27% (95% CI, 15–41%; P=0.072) at 2 years, 19% (95% CI, 11–29%) versus 11% (95% CI, 4–23%; P=0.135) at 3 years, and 15% (95% CI, 7–25%) versus 0% at 5 years, respectively. There were no significant differences between groups in the preselected items of HRQoL assessment. Grade ≥3 systemic AEs were 46% in the TTFields/TMZ group versus 40% in the TMZ monotherapy group, without statistically significant difference between the two groups. The only TTFields-related AEs were reversible scalp skin reactions, with grades 1–2 and grade 3 skin reactions reported by 51% and 2% of patients, respectively.ConclusionsCombining TTFields with maintenance TMZ significantly improved PFS and OS in elderly patients with ndGBM in the phase 3 EF-14 clinical trial, without significant increases in systemic toxicity or negatively affecting patient HRQoL. TTFields-related skin AEs were low-grade and manageable.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT00916409, identifier: NCT00916409.

ENGOT-en11/GOG-3053/KEYNOTE-B21: Phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with newly diagnosed high-risk endometrial cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5608-TPS5608
Author(s):  
Toon Van Gorp ◽  
Mansoor Raza Mirza ◽  
Alain Lortholary ◽  
David Cibula ◽  
Axel Walther ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Endometrial Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Combination Therapy ◽  
Stage I ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Eortc Qlq

TPS5608 Background: Pembrolizumab, a selective humanized anti–PD-1 monoclonal antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% ORR as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer (EC). ENGOT-en11/GOG-3053/KEYNOTE-B21 is a phase 3, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC. Methods: Eligible patients are ≥18 years old with newly diagnosed, histologically confirmed high-risk (stage I/II non-endometrioid, stage III/IVa, p53 abnormality) EC (carcinoma or carcinosarcoma) following surgery with curative intent with no evidence of disease post-operatively or on imaging, and without prior systemic therapy/radiotherapy. In total, ̃990 patients are randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles + chemotherapy (carboplatin area under the curve [AUC] 5 or 6 + paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2 or 2.7 + paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2 per their treatment assignment. At the investigator’s discretion, radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and International Federation of Gynecology and Obstetrics (FIGO) surgical stage (I/II vs III/IVA). Dual primary endpoints are disease-free survival (DFS; per investigator assessment) and overall survival (OS), both estimated by the Kaplan-Meier method, with a stratified log-rank test to assess treatment differences and a Cox proportional hazard model with Efron’s method of tie handling to assess the magnitude of treatment differences. Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and Endometrial Cancer Module [EORTC QLQ-EN24]). The study began enrollment in December 2020. Clinical trial information: NCT04634877.

scholarly journals Tapentadol Prolonged Release for Severe Chronic Osteoarthritis Pain in the Elderly—A Subgroup Analysis of Routine Clinical Practice Data

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Andreas Schwittay ◽  
Melanie Sohns ◽  
Birgit Heckes ◽  
Christian Elling
Keyword(s):  
Quality Of Life ◽  
Clinical Practice ◽  
Elderly Patients ◽  
Subgroup Analysis ◽  
The Elderly ◽  
Routine Clinical Practice ◽  
Prolonged Release ◽  
Younger Patients ◽  
Quality Of Life Measures

Background. Tapentadol prolonged release (PR) has been shown effective and generally well tolerated in a broad range of chronic pain conditions. This subgroup analysis investigated its benefits for elderly patients with severe chronic osteoarthritis (OA) pain in routine clinical practice. Patients and Methods. Data of all patients with chronic OA pain were extracted from the database of a prospective, 3-month noninterventional tapentadol PR trial. The data of elderly OA patients (>65 years of age; n = 752) were compared with the data of younger OA patients (≤65 years; n = 282). Results. Almost all patients (elderly 98.7% and younger patients 99.3%) had received long-term analgesic medication prior to the start of tapentadol PR treatment but presented with severe pain accompanied by considerable impairments in sleep quality and quality of life measures. Tapentadol PR provided effective pain relief in both patient groups, with slightly better outcomes in younger patients. However, the mean baseline pain intensity of 7.1 (SD 1.5) was reduced by 3.8 points (p≤0.001), and sleep and quality of life measures had also markedly improved in the elderly: quality of sleep by 3 points, quality of life by 3.4 points, social activities by 3 points, and independence by 2.7 points (p≤0.001 for all measures; 11-point scale). At the end of observation, 68% of the elderly had clinically relevant pain reductions of at least 50% (vs baseline), and 87.9% attained either their intended pain reduction target and/or an additional individual treatment target (both predefined during baseline examination). Only 8.4% of the elderly experienced adverse drug reactions, most frequently nausea (2.7% of patients) and dizziness (1.5%). Conclusion. Tapentadol PR provided effective and well-tolerated treatment of severe chronic OA pain for elderly patients in routine clinical practice. The favorable tolerability profile in particular suggests tapentadol PR as a treatment option before classical strong opioids are considered.

The quality of life of patients with newly diagnosed M1 prostate cancer: Experience with EORTC clinical trial 30853

1996 ◽  
Vol 32 (1) ◽  
pp. 72-77 ◽  
Author(s):  
F.C. da Silva ◽  
S.D. Fossa ◽  
N.K. Aaronson ◽  
S. Serbouti ◽  
L. Denis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Clinical Trial ◽  
Newly Diagnosed ◽  
Cancer Experience

Melphalan, Prednisone and Lenalidomide Followed by Lenalidomide Maintenance Displays Treatment Characteristics Favourable to Global Quality of Life in Newly Diagnosed Multiple Myeloma (NDMM) Patients ≥ 65 Years,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3988-3988 ◽  
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Antonio Palumbo ◽  
Roman Hajek ◽  
Martin Kropff ◽  
Maria Teresa Petrucci ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Partial Response ◽  
Progressive Disease ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Risk Of Disease ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 3988 Background: Melphalan, prednisone and lenalidomide followed by lenalidomide maintenance (MPR-R) demonstrated higher response rates (ORR; 77% vs. 50%, p <.001; VGPR or better: 32% vs. 12%, p <.001) and significantly reduced the risk of disease progression (hazard ratio [HR] = 0.423, p <.001) vs. MP alone [Palumbo, 2010]. Alongside efficacy considerations, analyses on health-related quality of life (HRQoL) may help more fully establish a regimen's overall treatment profile. HRQoL improvements with MPR-R were observed during MPR induction as well as lenalidomide maintenance, documenting a well-balanced profile in terms of efficacy, tolerability and HRQoL [Dimopoulos, 2011]. Alternative findings on novel NDMM treatment have shown efficacy of melphalan, prednisone and bortezomib (VMP) treatment to be associated with an intermittent deterioration in patients' HRQoL [Dhawan, 2009]. Methods: A mixed effects model was developed based on parameters pre-selected as potentially clinically relevant in impacting HRQoL. Models were run on six domains pre-selected based on clinical relevance: Global QoL, Physical Functioning, Fatigue and Pain (from EORTC QLQ-C30), and Disease Symptoms and Side Effects of Treatment (from EORTC MY20). Cycle 16 was determined as the last observation time point with a statistically meaningful sample size at time of follow-up (May 2010). Following explanatory variables were included: time-dependant covariates at individual HRQoL measurement time points (i.e. cycle 4, 7, 10, 13 and 16), treatment group (MPR-R vs. MP), gender (Female vs. Male), age, baseline QoL, Partial Response (PR) vs. Stable Disease (SD) and Very Good Partial Response or better (≥VGPR) vs. SD, Progressive Disease (PD) and Discontinuation (DC). Neutropenia and anemia, both Grade 3 or 4, were considered the clinically most relevant safety parameters. Main results for Global QoL are reported, with results from other domains found to be comparable. Results: Across all time-dependant covariates, a statistically significant reduction on Global QoL (−4.63; p=.004) was observed at Cycle 4. Being female vs. male significantly reduced Global QoL by -−.07 (p=.026). Each additional life year was found to lower Global QoL b− −0.40 points (p=.034). Baseline Global QoL was also significant, each additional score point leading to +0.30 (p <.001). A response level of ≥VGPR vs. SD increased Global QoL by 9.11 (p=.023); Progressive Disease (PD) reduced Global QoL by -−.34 score points (p <.001). All other pre-defined variables did not significantly impact Global QoL. Clinically meaningful changes for Global QoL in the underlying patient population have been determined to constitute at least a 7-point change [Dimopoulos, 2011]. Progressive disease (reducing Global QoL), respectively ≥VGPR (increasing Global QoL) exerted clinically meaningful changes, as did anemia grade 3–4, which had a clinically meaningful, but not statistically significant negative impact (−9.85; p=.057). Although no significant direct effect of MPR-R over MP on Global QoL was detected in the underlying model, MPR-R displays properties which favor an improved HRQoL profile, including a stronger delay in PD and higher % of VGPR vs. MP patients. Furthermore, certain properties more frequently observed with MPR-R than MP (neutropenia grade 3 or 4 and discontinuation, DC) were shown not to have a significant impact on HRQoL. Anemia grade 3 or 4, exerted a clinically meaningful negative effect but was not significantly more often observed with MPR-R compared to MP (24% vs. 17%, p= 0.091). Conclusions: More patients achieved ≥VGPR when receiving continuous MPR-R treatment than those receiving MP. In the above pooled analysis, ≥VGPR was shown to improve Global QoL in a clinically meaningful and statistically significant way. Furthermore, progression was also shown to negatively impact Global QoL (−8.34; p <.001), with MPR-R significantly reducing the risk of disease progression over MP. Delaying progression with continuous MPR-R therefore helps to maintain a high Global QoL. Disclosures: Dimopoulos: Celgene: Consultancy, Honoraria. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma. Palumbo:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Ortho-Biotech: Honoraria. Hajek:Celgene: Honoraria; Janssen-Cilag: Honoraria; Merck: Honoraria. Petrucci:Celgene: Honoraria. Lewis:Celgene: Employment, Equity Ownership. Millar:Celgene: Consultancy. Zhang:Celgene: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. Delforge:Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Speakers Bureau.

Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: BIBABRAX study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4615-4615 ◽  
Author(s):  
Jaime Feliu Batlle ◽  
Monica Jorge Fernandez ◽  
Teresa Macarulla ◽  
Bartomeu Massuti ◽  
Ana Albero ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Performance Status ◽  
Locally Advanced ◽  
Standards Of Care ◽  
Ecog Ps

4615 Background: FOLFIRINOX and nab-paclitaxel plus gemcitabine (nab-P+G) are the standard of care in the first-line treatment of mPC patients (pt) with good performance status. However, no standards of care exist for elderly ( > 70 years) pt as they are usually excluded in clinical trials. This study aimed to evaluate whether the clinical benefit of nab-P+G could be extended to elderly pt with mPC. Methods: This was an open-label, single-arm, multicenter, phase II trial, to assess the efficacy and safety of Nab-P+G in elderly pt (≥ 70 years) with ECOG PS 0–1 and untreated unresectable locally advanced or metastatic PC. Pt received four-week cycles of intravenous (i.v.) nab-paclitaxel 125 mg/m2, followed by i.v. gemcitabine 1,000 mg/m2, on days 1, 8 and 15, until disease progression. Efficacy was evaluated according RECIST v 1.1 criteria and safety according NCI-CTCAE v 4.0 criteria. Results: Eighty pt were enrolled in the study. Median age was 74.6 years (range 70-87.9), 57.5% were men, 71% had ECOG PS 1 and 86% metastatic disease. 16.3% of patients had a history of prior tumor surgical resection, 12.5% received chemotherapy and 3.8% radiotherapy. Primary tumor was located in head (32.5%), tail (25.0%) and body (22.5%). Nab-P and G was reduced in 49% and 41% of pt respectively. 15 pt definitely interrupt study treatment due to toxicity: neurotoxicity (7), asthenia (5), neutropenia (1), leukocytosis (1) and hepatotoxicity (1). Time until definite deterioration (reduction ≥10 points as compared to baseline in EORTC-QLQ C30) was 1.6 months and deterioration-free rate at 3 months was 54.3%. Overall response rate was 13.8%, clinical benefit rate 67.5%, median PFS 7.2 months and median OS 9.2 months. The most common treatment-related adverse events were asthenia (60.0%), diarrhea (40.0%), neutropenia (33.8%), hair loss (28.8%), thrombocytopenia (26.3%), and nausea (23.8%). Only asthenia and neutropenia presented a relatively high incidence of grade 3 and 4 toxicities (21.3%). At least 1 SAE was reported in 55% of pt. Conclusions: BIBABRAX study confirms the clinical benefit of nab-P+G in an elderly population with mPC, in terms of survival, clinical response and tolerance, therefore it could be considered a treatment option for elderly patients. However, it was unable to demonstrate the preplanned benefit on the quality of life. Further research is needed on treatment strategies that could reduce deterioration of the quality of life in these pt. Clinical trial information: NCT02391662 .

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