| 1. |
- Pellat, A., et al.
(author)
-
Comprehensive mapping review of real-world evidence publications focusing on targeted therapies in solid tumors : A collaborative work from ESMO real-world data and Digital Health Working Group
- 2023
-
In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S925-S925
-
Journal article (other academic/artistic)abstract
- Background: A growing body of real-world evidence (RWE) aims to better reflect outcomes of cancer patients treated in real-world settings. We aimed to conduct a first comprehensive mapping review of the RWE produced over the past 3 years in terms of tumor type, treatment strategies, setting, and data sources, focusing on targeted therapies (TT) in solid tumors.Methods: We conducted a systematic review in PubMed of RWE studies published between 01/2020 and 12/2022. We identified non-interventional studies using observational data, focusing on solid tumors exposure to targeted therapies, excluding immunotherapies. Abstract and full-text screening were performed by 11 independent reviewers.Results: A total of 7,774 publications were retrieved with 1,251 considered eligible and extracted. The number of publications per year progressively increased during this period (328 in 2020; 421 in 2021; 502 in 2022). Most studies (50%) were performed in Asia, followed by Europe (25%) and North America (17%). Only 8% of studies had patients treated in more than one country. Treatment effectiveness and safety were assessed in 71% and 42% of studies respectively. Main data sources were medical records.Conclusions: RWE publications on TT for solid tumors are heterogeneous and mostly rely on retrospective data such as medical records. Population-based and international studies are rare. Collaborative efforts towards international representativeness and the use of routinely collected and/or standardized data sources must be encouraged to increase the relevance and future quality of publications and their potential impact on oncology practice.
|
|
| 2. |
|
|
| 3. |
- Derksen, J. W. G., et al.
(author)
-
Real-world evidence contributions to European medicines agency's safety and efficacy evaluations of oncology targeted therapies between 2018-2022
- 2023
-
In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S930-S930
-
Journal article (other academic/artistic)abstract
- Background: While Real-world Evidence (RWE) has documented value for safety monitoring and disease epidemiology, its objective contribution to safety and efficacy evaluations for regulatory purposes is still unclear. Here, we aim to describe the prevalence and type of RWE considered by European Medicines Agency (EMA) as contribution to efficacy and safety-related evidence generation among approved oncology targeted therapies...Methods: On March 10, 2023, we screened the medicines listing of EMA to identify all anti-cancer targeted therapies for solid malignancies with a decision date (initial marketing authorizations and extension of indications) between 2018-2022. We screened the European public assessment reports (EPARs) using a standardized approach to collect data on RWE. When generated pre-authorization, the RWE contribution to the final regulatory decision was classified as definitive, supportive, or non-supportive. For...Results: Out of a total of 1976 medicines, we identified 55 oncology targeted therapies, corresponding to 75 EPARs (indications), which are described in the table. The use of RWE in regulatory deliberations occurred in 24/75 (32%) EPARs, increasing from 30% in 2018-2020, to 34% in 2021-2022. Pre-authorization RWE was described in 20/24 (83%) EPARs, among which none were definitive, 8 RWE studies (in 7 EPARs) non-supportive, and 20 RWE studies (in 15 EPARs) were supportive of the decision. Published RWE...Conclusions: Over the past 5 years, RWE involvement in the approval of oncology targeted therapies in Europe tends to increase, with the majority being supportive for EMA regulatory decision making complementary to traditional clinical trials...
|
|
| 4. |
|
|
| 5. |
- Karihtala, P., et al.
(author)
-
Current treatment landscape of HR+/HER2-advanced breast cancer in the Nordics : A modified Delphi study
- 2022
-
In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 33:Suppl. 3, s. S218-S218
-
Journal article (other academic/artistic)abstract
- Background: The aim of this Delphi study was to assess current perspectives on HR+/HER2- advanced breast cancer (aBC) treatment strategies among Nordic BC oncologists, and to gain broader understanding of the uptake and implementation of novel treatments.Methods: A modified, three round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection and questionnaires development. The questionnaires covered clinically relevant topics related to HR+/HER2- aBC treatment: treatment patterns in different lines of therapy (first- (1L), second- (2L) and third-line (3L)), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement.Results: In total 28 panelists participated in the study. In rounds one and two, 14 and 21 questions reached consensuses, respectively. Thirteen non-consensus reaching questions were reposted in round three, where 10 reached consensus. Overall, topics that reached a high consensus level included: treatment approaches in 1L and 2L treatment setting for HR+/HER2- aBC, treatment of oligometastatic disease, visceral crisis and brain metastases, and age-related treatment considerations. No consensus was reached for aspects regarding 3L therapy and de novo aBC. Endocrine therapy (ET) combined with CDK4/6i was the treatment of choice for both 1L and 2L therapy. Regarding implementation of clinical guidelines, a discrepancy was observed between treatments recommended in guidelines and those used in clinical practice, especially in cases where novel treatments were proposed.Conclusions: Endocrine therapy combined with a CDK4/6i is the frontline treatment choice for HR+/HER2- aBC in the Nordics. Observed discrepancies between international clinical guidelines and practice are partly due to difference in the availability of novel treatment strategies that might lead to differences in clinical experience in the Nordics. The lack of consensus might reflect limited evidence on these topics and the need for collaborative research efforts. Written on behalf of Nordic Delphi Panellist group.
|
|
| 6. |
- Kofteridis, Diamantis P., et al.
(author)
-
Factors Influencing Non-albicans Candidemia : A Case-Case-Control Study
- 2017
-
In: Mycopathologia. - : Kluwer Academic Publishers. - 0301-486X .- 1573-0832. ; 182:7-8, s. 665-672
-
Journal article (peer-reviewed)abstract
- The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.
|
|
| 7. |
- Nicolaescu, T-M, et al.
(author)
-
Prognostic relevance of pre-treatment c-reactive protein to albumin ratio in patients with diffuse large b cell lymphoma
- 2022
-
In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 33:7, s. S832-S832
-
Journal article (other academic/artistic)abstract
- Background: Previous studies have shown that a high level of pre-treatment C-reactive protein to albumin ratio (CAR) is associated with poor outcomes in patients with diffuse large B cell lymphoma (DLBCL). However, these were single-centre studies with a relatively small number of patients. The aim of our study was to further investigate the prognostic value of CAR in a larger cohort and whether the addition of CAR to the International Prognostic Index (IPI) would result in a better discriminatory ability.Methods: All adult patients treated 2000–2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n=414). The study population was divided into high respectively low CAR group using the Budczies et al.’s cut-off finder. The groups were compared in terms of differences in clinical characteristics, response to treatment and survival. The prognostic ability of IPI vs IPI plus CAR was compared by receiver-operating-characteristic curve (ROC), net reclassification improvement (NRI) and the integrated discrimination improvement index (IDI).Results: The high CAR group was associated with higher IPI score, lower performance status, high LDH, bulky disease and more advanced Ann Arbour stage. The high CAR group had a higher proportion of patients with progressive disease (24.2% vs 6.4%, p<0.001) and a lower proportion of patients with complete remission (61.5% vs 85.7%, p<0.01). The high CAR group had poorer 5-year OS (49% vs 70%; p<0.001) and EFS (45% vs 68%; p<0.001). After adjustment for BMI, bulky disease and IPI, high CAR values independently predicted poor OS (HR: 1.58, 95% CI 1.18–2.11; p=0.002) and EFS (HR: 1.57, 95% CI 1.18–2.10; p=0.002). When assessed by NRI, the addition of CAR to IPI seems to better identify patients with better prognosis compared with IPI alone. However, the area under the ROC curve and IDI did not show any significant improvement in model performance.Conclusions: CAR seems to be a useful prognostic biomarker in patients with DLBCL. Although the addition of CAR to IPI could identify some additional patients with better prognosis, the discriminatory ability of IPI was not improved. IPI remains the standard model for risk stratification in patients with DLBCL.
|
|
| 8. |
- Rodriguez-Wallberg, Kenny A., et al.
(author)
-
ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden : a phase III randomised double-blinded placebo-controlled study
- 2023
-
In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:12
-
Journal article (peer-reviewed)abstract
- Background Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.Methods and analysis A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14–42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.Ethics and dissemination This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.Study registration The National Institutional review board in Sweden dnr:2021–03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.Trial registration number NCT05328258; EudraCT number:2020-004780-71.
|
|
| 9. |
- Schiza, Aglaia, et al.
(author)
-
Predictive role of HER2-status on the effectiveness of endocrine adjuvant treatment in postmenopausal breast cancer patients : a population-based cohort study
- 2021
-
In: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 186, s. 779-789
-
Journal article (peer-reviewed)abstract
- PURPOSE: There are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade.METHODS: A population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively.RESULTS: After propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34-0.77, p value < 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41-1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14-5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10-3.38, p = 0.345).CONCLUSION: Our study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.
|
|
| 10. |
- Valachis, A., 1984-, et al.
(author)
-
Palbociclib dose patterns in Swedish patients with metastatic breast cancer : 5-year update from the SIRI study
- 2023
-
In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S362-S362
-
Journal article (other academic/artistic)abstract
- Background: Although palbociclib combined with endocrine therapy is a well-established treatment option in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), there is limited evidence on patterns of dose reductions in real-world setting. The Swedish Ibrance Registries Insights (SIRI) study investigated real-world dose patterns using a nationwide cohort of palbociclib-treated MBC patients...Methods: This was a retrospective study utilizing population-based Swedish Health Data Registers. The cohort included all patients ≥ 18 years with ≥ 1 dispensation of palbociclib from January 2017 – June 2022. Minimum follow-up was 3 months. Starting dose and dose changes for the full population and for different age groups, in total and over time, was investigated...Results: 2058 patients were identified and the median (IQR) age at treatment initiation was 68.4 (15.7) years. Patients were stratified into three age groups: <50, 50-69, ≥70 years, with the following distribution: 9.9%, 46.1%, and 44.0%, respectively. Most patients were initiated on 125 mg (82.0%), with a lower share for older patients (≥70 years; 74.4%). In total, 45.5% of patients had ≥ 1 dose reduction, with a higher frequency for older patients (≥70 years; 48.5%). Median (IQR) time to first dose...Conclusions: Most Swedish palbociclib-treated patients were initiated on the recommended dose, but a lower starting dose and a higher frequency of dose reductions were observed for older patients. The time to dose reduction was equal across age groups, whereas the probability for dose reduction increased over time for older patients, and for patients with a start dose of 100 mg...
|
|
