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1.
BMC Cancer ; 24(1): 887, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044160

RESUMEN

BACKGROUND: In the pivotal phase III RECOURSE trial, trifluridine/tipiracil (FTD/TPI) improved progression-free and overall survival (PFS, OS) of patients with pre-treated metastatic colorectal cancer (mCRC). Subsequently, the TALLISUR trial provided post-authorisation efficacy and safety data and patient-reported outcomes on quality of life (QoL) in a German patient cohort. The present analysis reports the final data on efficacy, safety and QoL and investigates the impact of baseline characteristics and associated prognostic subgroups on outcome. METHODS: In this prospective, multi-centre, Germany-wide, phase IV study, patients with pre-treated mCRC were given the choice to receive either FTD/TPI or best supportive care (BSC). To assess the primary endpoint, QoL, EORTC QLQ-C30 questionnaires were employed. Secondary endpoints included QoL assessed through EQ-5D-5L questionnaires, OS, PFS and safety. Additionally, 3 subgroups were defined according to a post-hoc analysis of the RECOURSE trial: best, good and poor prognostic characteristics (BPC, GPC, PPC). Patients with < 3 metastatic sites at inclusion and/or ≥ 18 months from diagnosis to inclusion were considered to have GPC. GPC patients without liver metastasis at inclusion were considered to have BPC. All remaining patients were considered to have PPC. RESULTS: Of 195 patients, 186 decided to receive FTD/TPI and 9 to receive BSC. The low number of patients in the BSC-arm did not allow statistically meaningful analyses. Treatment with FTD/TPI was associated with maintained QoL. For all patients, median OS was 6.9 months (95% CI 6.1 - 8.3) and for the defined subgroups (BPC n = 20 vs GPC n = 65 vs PPC n = 121) 12.2, 7.9 and 6.8 months (95% CI 6.0 - 18.2, 6.2 - 13.3, 5.4 - 8.1). The most frequent TEAEs were neutropenia (29.6%), anaemia (24.7%) and nausea (23.7%). Febrile neutropenia occurred in 1.1%. CONCLUSIONS: Treatment of patients suffering from pre-treated mCRC with FTD/TPI was associated not only with prolonged survival and delayed progression, but also with maintained QoL. Independent of other baseline characteristics such as ECOG performance status and age, low metastatic burden and indolent disease were factors associated with favourable outcome. CLINICAL TRIAL REGISTRATION: EudraCT-Number 2017-000292-83, first registration 19/06/2017.


Asunto(s)
Neoplasias Colorrectales , Combinación de Medicamentos , Pirrolidinas , Calidad de Vida , Timina , Trifluridina , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Pirrolidinas/uso terapéutico , Trifluridina/uso terapéutico , Trifluridina/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años , Metástasis de la Neoplasia , Supervivencia sin Progresión , Pronóstico , Alemania
2.
Artículo en Inglés | MEDLINE | ID: mdl-38960600

RESUMEN

OBJECTIVE: An effective tool for establishing concordant end-of-life (EOL) care in patients with cancer is advance care planning (ACP). However, various barriers, including psychological obstacles, hamper the access to ACP. Therefore, a new conceptual model combining a psycho-oncological approach with structured ACP was developed. The effectiveness and efficiency of this new concept of collaborative ACP (col-ACP) is evaluated in the present randomised controlled trial in patients with palliative cancer. METHODS: 277 patients with palliative cancer and their relatives were randomised into three groups (1) collaborative ACP (col-ACP) consisting of a psycho-oncological approach addressing barriers to EOL conversations followed by a standardised ACP procedure, (2) supportive intervention (active control) and (3) standard medical care. RESULTS: Patients in the col-ACP group completed advance directives (p<0.01) and healthcare proxies (p<0.01) significantly more often. Additionally, they felt better planned ahead for their future treatment (p<0.01) and were significantly more confident that their relatives were aware of their treatment wishes (p=0.03). In fact, their goals of care were known and highly fulfilled. However, patients' and caregivers' quality of life, patients' stress, depression and peace did not differ between the groups. CONCLUSIONS: The new, well-received, concept of col-ACP improves readiness and access to ACP and results in more consistent EOL care. Further, even if no direct influence on quality of life could be proven, it supports patients in planning their treatment, making autonomous decisions and regaining self-efficacy in the face of life-limiting cancer. Therefore, a closer interlocking and information exchange between psycho-oncological and ACP services seems to be reasonable. TRIAL REGISTRATION NUMBER: NCT03387436.

3.
Cancers (Basel) ; 16(8)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38672643

RESUMEN

Background: Precision oncology treatments are being applied more commonly in breast and gynecological oncology through the implementation of Molecular Tumor Boards (MTBs), but real-world clinical outcome data remain limited. Methods: A retrospective analysis was conducted in patients with breast cancer (BC) and gynecological malignancies referred to our center's MTB from 2018 to 2023. The analysis covered patient characteristics, next-generation sequencing (NGS) results, MTB recommendations, therapy received, and clinical outcomes. Results: Sixty-three patients (77.8%) had metastatic disease, and forty-four patients (54.3%) had previously undergone three or more lines of systemic treatment. Personalized treatment recommendations were provided to 50 patients (63.3%), while 29 (36.7%) had no actionable target. Ultimately, 23 patients (29.1%) underwent molecular-matched treatment (MMT). Commonly altered genes in patients with pan-gyn tumors (BC and gynecological malignancies) included TP53 (n = 42/81, 51.9%), PIK3CA (n = 18/81, 22.2%), BRCA1/2 (n = 10/81, 12.3%), and ARID1A (n = 9/81, 11.1%). Patients treated with MMT showed significantly prolonged progression-free survival (median PFS 5.5 vs. 3.5 months, p = 0.0014). Of all patients who underwent molecular profiling, 13.6% experienced a major clinical benefit (PFSr ≥ 1.3 and PR/SD ≥ 6 months) through precision oncology. Conclusions: NGS-guided precision oncology demonstrated improved clinical outcomes in a subgroup of patients with gynecological and breast cancers.

4.
J Clin Oncol ; 42(4): 410-420, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37963317

RESUMEN

PURPOSE: This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA). METHODS: DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B). RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups. CONCLUSION: Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.


Asunto(s)
Adenocarcinoma , Anticuerpos Monoclonales Humanizados , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/uso terapéutico , Docetaxel/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/patología , Fluorouracilo/efectos adversos , Leucovorina/efectos adversos , Terapia Neoadyuvante/métodos , Oxaliplatino/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología
5.
Artículo en Inglés | MEDLINE | ID: mdl-37979957

RESUMEN

OBJECTIVES: Advance care discussions are a useful communication tools for medical preferences and beneficial for shared decision-making processes in hospital settings. The present study developed the first screening tool for need for advance care planning (ACP). METHODS: In phase 1 (n=92), items were evaluated using feasibility analysis and item reduction. In phase 2 (n=201), reduced screening items were analysed for predictive value of need for ACP. Statistical analysis included receiver-operating characteristics analysis (area under the curve>0.80), optimal cut-off based on sensitivity and specificity, interpretation of OR and construct validity using correlation with death anxiety, communication avoidance within families and trust based on the relationship with the treating physician. RESULTS: Participants in both phases were approximately 60 years old with non-curative prognosis. After item reduction, predictive values of four possible items with good item difficulty and discrimination were compared for mild, moderate and great levels of death anxiety. A two-item combination of I am burdened by thoughts of an unfavourable course of the disease and I am burdened by the feeling of being ill-prepared for the end of life showed best prediction of death anxiety and communication avoidance. Clinical cut-off at sum-score ≥6 was of high sensitivity (95%) and specificity (81%). Previous use of social support and readiness for ACP was related to higher chance of interest in ACP. CONCLUSION: Screening for need of ACP is possible with two objective items and one subjective item. Positive screening therefore indicates when to offer ACP discussions and provides routine estimation of ACP need in clinical practice.

6.
Psychooncology ; 32(12): 1867-1875, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37905904

RESUMEN

BACKGROUND: Advance care planning (ACP) can help to elicit cancer patients' preferences in a discussion process to promote person-centred medical decision-making. Expectations are known to be highly relevant determinants of decisional processes. So far, however, little is known about cancer patients' expectations of ACP that lead to acceptance or refusal of the programme. The presented study, therefore, aims to explore cancer patients' expectations of ACP. METHODS: Semi-structured interviews were conducted with a purposeful sample of 27 cancer patients consenting to or refusing a newly implemented ACP programme in a German university hospital. Data were analysed using typological content analysis. RESULTS: We identified five different expectation clusters in relation to ACP. Consenting participants held expectations about the impact of ACP that were either 'ego-centred' or 'family-centred'. Refusers had expectations based on ignorance and misinformation, or-if they had already completed an advance directive-expectations to avoid unpleasant redundancy, perceiving no additional benefit but a burden from ACP. Finally, refusers in particular expressed expectations of delegated responsibility at the end of life, including anticipation of proxy decision-making. CONCLUSION: Our study results suggest that expectation-modifying measures could be taken to positively influence cancer patients' expectations and thus the acceptance of ACP. In this respect, reducing ignorance and misguided expectations plays a decisive role. Especially in family constellations with expected delegation of responsibility and dependence at the end of life, it might be important to promote ACP as a family-intervention to improve family outcomes.


Asunto(s)
Planificación Anticipada de Atención , Neoplasias , Cuidado Terminal , Humanos , Motivación , Directivas Anticipadas , Prioridad del Paciente , Muerte , Neoplasias/terapia
7.
BMC Palliat Care ; 22(1): 100, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37480117

RESUMEN

BACKGROUND: The number of palliative care patients with complex needs is increasing in developed countries. In addition to physical aspects and symptom control, psychosocial aspects are of great importance for palliative care patients. The aim of this study was to understand which psychosocial aspects are important to patients, relatives and health professionals within the setting of a palliative care unit in comparison with specialised palliative home-care (SPHC). METHODS: We used a qualitative design based on semistructured interviews, which were coded via qualitative content analysis. The study took place in the state of Hesse, Germany, and data collection was conducted in 2017 (interviews from the ELSAH study, which was conducted in a SPHC) and 2018 (supplementary interviews conducted in a palliative care unit). The results from both settings were compared. RESULTS: In the palliative care unit, 10 health professionals, 11 patients and 8 relatives were interviewed. In the outpatient setting, we interviewed 30 health professionals, 14 patients and 14 relatives. We identified four key psychosocial issues related to palliative care that were relevant in both the inpatient and outpatient settings: care planning, patient-centred care, a protected environment with feelings of safety, and psychological well-being. In addition, immediate availability of medical staff, greater relief of the relatives and better accessibility of psychological care were more important in the inpatient setting than in the specialised palliative home care setting. CONCLUSIONS: Knowledge and application of the identified key issues may improve patient-centred palliative care. Accessibility of psychological care and immediate availability of medical staff may be important factors for enhancing psychological well-being in the inpatient palliative care setting. Consideration of the identified key issues may help to develop more collaborative transitions between the palliative care unit and the SPHC and may help to provide palliative care patients and their families with care that is appropriate and feasible for them. TRIAL REGISTRATION: The underlying comparative study of the outpatient setting of specialised palliative home-care (ELSAH) was registered within the German Clinical Trials Register DRKS-ID: DRKS00012421, ( https://drks.de/search/de/trial/DRKS00012421 ) on 19th May 2017.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Enfermería de Cuidados Paliativos al Final de la Vida , Humanos , Cuidados Paliativos , Pacientes Internos , Pacientes Ambulatorios
8.
Int J Cancer ; 153(1): 141-152, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-36757197

RESUMEN

Real-world data on the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) are still limited. The NEPTUN study evaluated effectiveness and safety of first-line nab-paclitaxel (Abraxane) plus carboplatin (nab-P/C) in patients with advanced NSCLC in routine clinical practice in Germany. Patients included in our study were aged ≥18 years, diagnosed with locally advanced or metastatic NSCLC and with decision for first-line nab-P/C in routine clinical practice. Primary objective was 6-month progression-free survival rate (PFS6), secondary objectives included overall survival (OS), overall response rate (ORR) and safety. From 2016 to 2019, 408 patients from 75 sites were enrolled. PFS6 was 39.5% (95% CI: 34.2-44.8), median PFS was 5.1 months (95% CI: 4.6-5.6), ORR was 42.9% (95% CI: 37.7-48.2). Median OS was 10.5 months (95% CI: 9.2-11.6). In subgroup analyses, median OS for squamous vs non-squamous histology was 11.5 months (95% CI: 9.2-13.8) vs 9.8 months (95% CI: 8.1-11.3) and for patients aged ≥70 vs <70 years median OS was 12.4 months (95% CI: 9.8-15.1) vs 9.6 months (95% CI: 7.7-11.1). Adverse events (AEs) related to nab-paclitaxel were reported in 247 (66.4%) patients, while carboplatin-related AEs were documented in 224 (60.2%) patients. Most frequently related AEs were leukopenia (22.3%) for nab-paclitaxel and anemia (20.2%) for carboplatin. Nab-P/C-related deaths were reported in 2 (0.5%) patients (sepsis and neutropenic sepsis). No new or unexpected safety signals emerged. These results support the effectiveness and safety of first-line nab-P/C in patients with advanced NSCLC reported in the pivotal trial and highlight the clinical value of this regimen in the real-world setting.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Adolescente , Adulto , Carcinoma de Pulmón de Células no Pequeñas/patología , Carboplatino/efectos adversos , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Paclitaxel/efectos adversos
9.
Eur J Cancer Care (Engl) ; 31(6): e13756, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36268891

RESUMEN

OBJECTIVES: The objective of this study is to develop a care pathway for a hospital-based advance care planning service for cancer patients. METHODS: A web-based modified Delphi study consulted an expert panel consisting of a convenience sample of stakeholders including professionals with a special interest in advance care planning as well as a 'public and patient involvement group'. After generating ideas for core elements of a care pathway in the first round, numerical ratings and rankings informed the multi-professional research steering group's decision process eventually resulting in a final pathway. RESULTS: The 41 participants in the Delphi study identified 177 potential core elements of the pathway in the first round. In two further rounds, consensus was reached on a final version of the pathway with 148 elements covering the 10 domains: prerequisites, organisation and coordination, identification and referral, provision of information, information sources, family involvement, advance care planning discussion, documentation, update and quality assurance. CONCLUSION: We propose a care pathway for advance care planning for hospital patients with cancer based on the results of a Delphi study that reached consensus on an implementation strategy. Our study pioneers the standardisation of the process and provides input for further policy and research with the aim of aligning cancer patients' care with their preferences and values.


Asunto(s)
Planificación Anticipada de Atención , Neoplasias , Humanos , Técnica Delphi , Vías Clínicas , Hospitales , Neoplasias/terapia
10.
Cancers (Basel) ; 14(18)2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36139590

RESUMEN

BACKGROUND: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. METHODS: We retrospectively analyzed all patients referred to our center's Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel's target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS. RESULTS: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy (n = 30) had significantly longer progression-free survival than patients treated with other therapies (n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits. CONCLUSION: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches.

11.
JAMA Oncol ; 8(8): 1150-1158, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35737383

RESUMEN

Importance: In metastatic esophagogastric adenocarcinoma (EGA), the addition of programmed cell death 1 (PD-1) inhibitors to chemotherapy has improved outcomes in selected patient populations. Objective: To investigate the efficacy of trastuzumab and PD-1 inhibitors with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors or FOLFOX in first-line treatment of advanced ERBB2-positive EGA. Design, Setting, and Participants: This phase 2 multicenter, outpatient, randomized clinical trial with 2 experimental arms compared with historical control individually was conducted between March 2018 and May 2020 across 21 German sites. The reported results are based on a median follow-up of 14.3 months. Patients with previously untreated, metastatic ERBB2-positive (local immunohistochemistry score of 3+ or 2+/in situ hybridization amplification positive) EGA, adequate organ function, and eligibility for immunotherapy were included. Data analysis was performed from June to September 2021. Interventions: Patients were randomized to trastuzumab and nivolumab (1 mg/kg × 4/240 mg for up to 12 months) in combination with mFOLFOX6 (FOLFOX arm) or ipilimumab (3 mg/kg × 4 for up to 12 weeks) (ipilimumab arm). Main Outcomes and Measures: The primary end point was survival improvement with a targeted increase of the 12-month overall survival rate from 55% (trastuzumab/chemotherapy-ToGA regimen) to 70% in each arm. Results: A total of 97 patients were enrolled, and 88 were randomized (18 women, 70 men; median [range] age, 61 [41-80] years). Baseline Eastern Cooperative Oncology Group performance status was 0 in 54 patients (61%) and 1 in 34 patients (39%); 66 patients (75%) had EGA localized in the esophagogastric junction and 22 in the stomach (25%). Central post hoc biomarker analysis (84 patients) showed PD-1 ligand 1 (PD-L1) combined positive score of 1 or greater in 59 patients (72%) and 5 or greater in 46 patients (56%) and confirmed ERBB2 positivity in 76 patients. The observed overall survival rate at 12 months was 70% (95% CI, 54%-81%) with FOLFOX and 57% (95% CI, 41%-71%) with ipilimumab. Treatment-related grade 3 or greater adverse events (AEs) and serious AEs occurred in 29 and 15 patients in the FOLFOX arm and in 20 and 17 patients in the ipilimumab arm, respectively, with a higher incidence of autoimmune-related AEs in the ipilimumab arm and neuropathy in the FOLFOX arm. Liquid biopsy analyses showed strong correlation of early cell-free DNA increase with shorter progression-free and overall survival and emergence of truncating and epitope-loss ERBB2 resistance sequence variations with trastuzumab treatment. Conclusions and Relevance: In this randomized clinical trial, trastuzumab, nivolumab, and FOLFOX showed favorable efficacy compared with historical data and trastuzumab, nivolumab, and ipilimumab in ERBB2-positive EGA. The ipilimumab arm yielded similar OS compared with the ToGA regimen. Trial Registration: ClinicalTrials.gov Identifier: NCT03409848.


Asunto(s)
Adenocarcinoma , Nivolumab , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Ipilimumab/efectos adversos , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Receptor de Muerte Celular Programada 1/uso terapéutico , Receptor ErbB-2 , Trastuzumab/efectos adversos
12.
BMJ Open ; 12(5): e058531, 2022 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-35545378

RESUMEN

OBJECTIVES: During serious illness, open communication with caregivers can ensure high-quality care. Without end-of-life communication, caregivers may become surrogates and decision-makers without knowing the patient's preferences. However, expectations and fears may influence the initiation of communication. The present study investigates differences between palliative patients with cancer and caregivers regarding expectations of end-of-life communication, end-of-life fears and experiences with end-of-life communication. DESIGN: A cross-sectional study using a semi-structured interview and a paper-based questionnaire SETTING: University Hospital in Germany. PARTICIPANTS: 151 participants: 85 palliative cancer patients (mean age: 62.8 years, 65.9% male) and 66 caregivers (mean age: 56.3 years, 28.8% male). PRIMARY AND SECONDARY OUTCOME MEASURES: Expectations, end-of-life fears and experiences of end-of-life discussions. RESULTS: Patients and caregivers wish for the patient to be self-determined. In general, participants reported more positive than negative expectations of end-of-life discussions. Importantly, concerns about emotionally burdening other person was rated much higher in an informal context than a professional context (F(1,149)=316 958, p<0.001, ηp²=0.680), even though the emotional relief was expected to be higher (F(1,149)=46.115, p<0.001, ηp²=0.236). Caregivers reported more fears about the last period of life and more fears about end-of-life discussions than palliative patients, whereas palliative patients tended to avoid the topics of death and dying to a greater extent. CONCLUSIONS: There seems to exist a 'self-other' asymmetry: palliative patients and their caregivers expect substantial personal relief when openly talking about end-of-life issues, but also expect the other person to be burdened by such communication. Professionals repeatedly need to initiate end-of-life communication.


Asunto(s)
Neoplasias , Cuidado Terminal , Cuidadores/psicología , Comunicación , Estudios Transversales , Muerte , Miedo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Motivación , Neoplasias/terapia , Cuidados Paliativos/psicología , Cuidado Terminal/psicología
13.
J Immunother ; 45(2): 89-99, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34908007

RESUMEN

Nivolumab was the first immune checkpoint inhibitor approved for use in advanced non-small cell lung cancer (NSCLC). This noninterventional, prospective cohort study investigates real-world effectiveness of nivolumab in pretreated NSCLC patients in Germany (Enlarge-Lung/CA209-580). Patients with squamous (SQ) or nonsquamous (NSQ) NSCLC previously treated for locally advanced or metastatic (stage IIIB/IV) disease received nivolumab according to the current Summary of Product Characteristics. Overall survival (OS) was the primary endpoint. Of 907 patients enrolled, 660 patients who were followed for at least 12 months across 79 study centers in Germany, were analyzed. Median OS was 11.2 months [95% confidence interval (CI), 9.1-12.9]; outcomes for the 418 patients with NSQ histology [13.1 mo (95% CI, 10.6-15.6)] were more favorable than outcomes for the 242 patients with SQ histology [8.9 mo (95% CI, 6.4-11.3)]. Patients' age, presence of distant or brain metastases, or line of therapy did not affect outcomes; however, patients with poor performance status (ECOG-PS ≥2, n=80) had shorter median OS [4.7 mo (95% CI, 3.1-5.4)]. This study represents one of the largest real-world cohorts providing outcomes of nivolumab in pretreated NSCLC. The results match well with the published evidence from pivotal clinical trials and demonstrate clinical effectiveness of nivolumab in advanced NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/efectos adversos , Estudios Prospectivos
14.
Front Oncol ; 12: 993611, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36605436

RESUMEN

Introduction: In metastatic colorectal cancer (mCRC), the efficacy of immune checkpoint blockade (ICB) has so far been limited to patients with microsatellite instability high tumors (MSI-H). Unfortunately, most mCRC patients suffer from non-immunogenic microsatellite stable (MSS) tumors. Therefore, new combinatorial strategies are urgently needed to enhance the immunogenicity of MSS tumors to finally increase the number of patients benefiting from ICB. Methods: The AVETUX trial aimed to combine the PD-L1 antibody avelumab with the standard of care chemotherapy combination FOLFOX and the anti-EGFR antibody cetuximab. Furthermore, we performed a central radiological review of the pre- and on-treatment computed tomography scans to better define the individual response to treatment. Results and Discussion: In total, 43 patients were treated of which 39 patients were confirmed as RAS/BRAF wildtype in central tissue review and finally response evaluated. A final progression-free survival (PFS) of 11.1 (range: 0.8 to 22.3 months) and a herein updated final overall survival (OS) of 32.9 months (range: 0.8 to 47.1 months) was reached. We observed a strong median depth of response of 67.5% tumor shrinkage and deepness of response correlated significantly with survival. On the other hand, early tumor shrinkage was not an indicator of better outcome at a cut-off of 20% (median values). In a next step, we correlated the individual best radiological response with potential ICB response biomarkers and found that the clonality and diversity, but not frequency of tumor infiltrating lymphocytes (TiLs) and peripheral blood mononuclear cells (PBMCs), strongly correlated with response. In summary, we report the final overall survival of the AVETUX trial and propose T cell clonality and diversity as a potential marker to predict response to chemo-immunotherapy combinations in MSS mCRC by performing a central radiological review. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03174405).

15.
Cancer Med ; 10(22): 8127-8137, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34668662

RESUMEN

BACKGROUND: Platinum-based chemotherapy remains a first-line standard of care for approximately 30% of patients with non-small cell lung cancer (NSCLC) not harboring a druggable alteration. Favorable efficacy and safety of the nab-paclitaxel/carboplatin (nab-P/C) combination was shown in the pivotal phase 3 trial. However, information on effectiveness of nab-P/C in a real-world setting in Germany is missing. The NEPTUN study prospectively investigated the effectiveness and safety of nab-P/C in patients with advanced NSCLC in a real-world setting. METHODS: Patients with advanced or metastatic NSCLC received first-line nab-P/C according to clinical routine. The primary endpoint was 6-month progression-free survival rate (PFS6). Other endpoints included further effectiveness parameters, safety and quality of life. Data were analyzed descriptively. RESULTS: 408 patients were enrolled. PFS6 was 40.8% (95% confidence interval [CI], 35.3-46.2); median PFS was 5.2 months (95% CI, 4.5-5.7). overall response rate was 41.5% (95% CI, 36.3-46.8). Median overall survival (OS) was 10.5 months (95% CI, 9.2-11.6). Subgroup analyses revealed median OS for squamous versus non-squamous histology (11.8 months [95% CI, 9.2-13.8] vs. 9.6 months [95% CI, 7.7-11.2]) and age ≥70 versus <70 years (11.7 months [95% CI, 9.4-14.3] vs. 9.6 months [95% CI, 7.5-11.2]). Most common treatment-emergent adverse events (TEAEs) were anemia (26.5%), leukopenia (25.7%), and thrombocytopenia (16.6%). Mostly reported grade 3/4 TEAEs were leukopenia (10.2%), anemia (8.6%), and pneumonia (5.1%). nab-paclitaxel-related deaths as reported by the investigator occurred in 0.8% of patients. CONCLUSION: These real-world data support the effectiveness and safety of nab-P/C as first-line treatment for patients with advanced NSCLC independent of tumor histology. The results are comparable with the pivotal phase 3 trial. No new safety signals emerged.


Asunto(s)
Albúminas/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/farmacología , Carboplatino/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/farmacología , Estudios Prospectivos
16.
Palliat Med ; 35(10): 1897-1907, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34479460

RESUMEN

BACKGROUND: Impaired readiness may hinder purposeful advance care planning in cancer patients. To reduce barriers to participation in end-of-life decision-making, a collaborative intervention was developed combining a psycho-oncological approach of dignity-based and cognitive-behavioural interventions, followed by a standardised advance care planning-process. AIM: To evaluate the novel collaborative advance care planning-approach by synthetising cancer patient and carer perspectives on communicational and relational effects. DESIGN: As a sub-project of a mixed-methods evaluation study, we conducted an inductive content analysis of qualitative interviews with advanced cancer patients and caregivers to deeply explore the focused impact of a collaborative advance care planning-approach on communication and relationship dynamics. SETTING/PARTICIPANTS: Twelve patients with advanced cancer and 13 carers who participated in a collaborative advance care planning-intervention. RESULTS: The collaborative advance care planning-approach was consistently evaluated positively by participants. Transcriptions of the semi-structured interviews were coded, analysed and merged under three main themes concerning communicational and relationship dynamics: action readiness, content readiness and impact on future communication and relationship. CONCLUSIONS: The novel intervention served to foster individual readiness - including action and content readiness - for advance care planning-discussions by addressing highly individualised barriers to participation, as well as specific end-of-life issues. In addition, societal readiness could be promoted. Although the brief psycho-oncological intervention could not fully meet the needs of all participants, it can be used to develop individual psychotherapeutic strategies to improve different facets of readiness. The collaborative advance care planning-approach might require more time and human resources, but could pioneer successful advance care planning.


Asunto(s)
Planificación Anticipada de Atención , Neoplasias , Cuidado Terminal , Cuidadores , Comunicación , Humanos , Neoplasias/terapia , Investigación Cualitativa
17.
Oncol Res Treat ; 44(9): 469-475, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34350870

RESUMEN

INTRODUCTION: On the one hand, sleep disorders in cancer patients are reported in 30-50% of cancer patients. On the other hand, specific causes for these sleep disorders are little known. This study was done to evaluate factors which may affect sleep of cancer patients. To our knowledge, this is the first study which includes return to work as one factor of sleep disturbance. METHODS: 107 patients with various types of cancer treated in 2 hospitals were interviewed with a battery of questionnaires after having given informed consent. The questionnaires intended to detect abnormalities of sleep and related pain, breathing disorders, restless legs syndrome, depression, rumination, medication, and psychosocial distress. The study was approved by the ethics committee of the University of Marburg. RESULTS: The analysis of the 6 sleep-related questionnaires indicated a sleep disorder of any kind in 68% of all patients. Insomnia symptoms were present in 48 patients (44.9%). Pain, depression, anxiety, and worries about the workplace were significantly related to sleep disorders. CONCLUSION: Sleep disorders are common in cancer patients. The causes are manifold and should be considered by caregivers during diagnosis, therapy, and aftercare of cancer patients. Tumour patients should actively be asked about sleep disorders. If these are present, they should be addressed, and as they have a large impact on quality of life, treatment options should be offered in cooperation with sleep specialists.


Asunto(s)
Neoplasias , Síndrome de las Piernas Inquietas , Trastornos del Sueño-Vigilia , Humanos , Neoplasias/complicaciones , Neoplasias/epidemiología , Calidad de Vida , Sueño , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología , Encuestas y Cuestionarios
18.
J Immunother Cancer ; 9(7)2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34315821

RESUMEN

BACKGROUND: In patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration. METHODS: We treated 43 patients with predominantly microsatellite stable RAS/BRAF wild-type mCRC on a phase II trial combining chemotherapy with the epidermal growth factor receptor antibody cetuximab and the programmed cell death ligand 1 (PD-L1) antibody avelumab. We performed next-generation gene panel sequencing for mutational typing of tumors and liquid biopsy monitoring as well as digital droplet PCR to confirm individual mutations. Translational analyses included tissue immunohistochemistry, multispectral imaging and repertoire sequencing of tumor-infiltrating T cells. Detected PD-L1 mutations were mechanistically validated in CRISPR/Cas9-generated cell models using qRT-PCR, immunoblotting, flow cytometry, complement-dependent cytotoxicity assay, antibody-dependent cytotoxicity by natural killer cell degranulation assay and LDH release assay as well as live cell imaging of T cell mediated tumor cell killing. RESULTS: Circulating tumor DNA showed rapid clearance in the majority of patients mirroring a high rate of early tumor shrinkage. In 3 of 13 patients expressing the high-affinity Fcγ receptor 3a (FcγR3a), tumor subclones with PD-L1 mutations were selected that led to loss of tumor PD-L1 by nonsense-mediated RNA decay in PD-L1 K162fs and protein degradation in PD-L1 L88S. As a consequence, avelumab binding and antibody-dependent cytotoxicity were impaired, while T cell killing of these variant clones was increased. Interestingly, PD-L1 mutant subclones showed slow selection dynamics reversing on avelumab withdrawal and patients with such subclones had above-average treatment benefit. This suggested that the PD-L1 mutations mediated resistance to direct antitumor effects of avelumab, while at the same time loss of PD-L1 reduced biological fitness by enhanced T cell killing limiting subclonal expansion. CONCLUSION: The addition of avelumab to standard treatment appeared feasible and safe. PD-L1 mutations mediate subclonal immune escape to avelumab in some patients with mCRC expressing high-affinity FcγR3a, which may be a subset experiencing most selective pressure. Future trials evaluating the addition of avelumab to standard treatment in MSS mCRC are warranted especially in this patient subpopulation. TRIAL REGISTRATION NUMBER: NCT03174405.


Asunto(s)
Antígeno B7-H1/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Escape del Tumor/genética , Antígeno B7-H1/farmacología , Línea Celular Tumoral , Humanos
19.
J Clin Oncol ; 39(13): 1468-1478, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33764808

RESUMEN

PURPOSE: Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC. METHODS: Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR. RESULTS: Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2- mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab. CONCLUSION: Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/mortalidad , Trastuzumab/uso terapéutico , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Tasa de Supervivencia
20.
JAMA Oncol ; 6(8): 1203-1209, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32584367

RESUMEN

Importance: ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life. Objective: To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients with mBC (phase 2). Design, Setting, and Participants: The MTD in phase 1 was assessed using a 3 + 3 design with capecitabine dose modification. Phase 2 was an open-label, randomized, international multicenter study of patients with mBC treated with T-DM1 plus capecitabine or T-DM1 alone. Eligible patients had previously treated ERBB2-positive mBC or LA/mGC with no prior chemotherapy treatment for advanced disease. Interventions: Patients in the phase 1 mBC cohort received capecitabine (750 mg/m2, 700 mg/m2, or 650 mg/m2 twice daily, days 1-14 of a 3-week cycle) plus T-DM1 3.6 mg/kg every 3 weeks. Patients with LA/mGC received capecitabine at the mBC phase 1 MTD, de-escalating as needed, plus T-DM1 2.4 mg/kg weekly. In phase 2, patients with mBC were randomized (1:1) to receive capecitabine (at the phase 1 MTD) plus T-DM1 or T-DM1 alone. Main Outcomes and Measures: The phase 1 primary objective was to identify the MTD of capecitabine plus T-DM1. The phase 2 primary outcome was investigator-assessed overall response rate (ORR). Results: In phase 1, the median (range) age was 54.0 (37-71) and 57.5 (53-70) years for patients with mBC and patients with LA/mGC, respectively. The capecitabine MTD was identified as 700 mg/m2 in 11 patients with mBC and 6 patients with LA/mGC evaluable for dose-limiting toxic effects. In phase 2, between October 2014 and April 2016, patients with mBC (median [range] age, 52.0 [28-80] years) were randomized to receive combination therapy (n = 81) or T-DM1 (n = 80). The ORR was 44% (36 of 81 patients) and 36% (29 of 80 patients) in the combination and T-DM1 groups, respectively (difference, 8.2%; 90% CI, -4.5 to 20.9; P = .34; clinical cutoff, May 31, 2017). Adverse events (AEs) were reported in 78 of 82 patients (95%) in the combination group, with 36 (44%) experiencing grade 3-4 AEs, and 69 of 78 patients (88%) in the T-DM1 group, with 32 (41%) experiencing grade 3-4 AEs. No grade 5 AEs were reported. Conclusions and Relevance: Adding capecitabine to T-DM1 did not statistically increase ORR associated with T-DM1 in patients with previously treated ERBB2-positive mBC. The combination group reported more AEs, but with no unexpected toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT01702558.


Asunto(s)
Ado-Trastuzumab Emtansina/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Capecitabina/administración & dosificación , Ado-Trastuzumab Emtansina/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptor ErbB-2 , Resultado del Tratamiento
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