14 research outputs found
Clinical benefit of cancer drugs approved in Switzerland 2010-2019
Background It is unknown to what extent cancer drugs approved in Switzerland by the Swissmedic fulfil criteria of clinical benefit according to the European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS), the American Society of Clinical Oncology Value Framework version 2 (ASCO-VF) and the Swiss OLUtool v2 (OLUtool). Patients and methods An electronic search identified studies that led to marketing authorisations in Switzerland 2010-2019. Studies were evaluated according to ESMO-MCBS, ASCO-VF and OLUtool. Substantial benefit for ESMO-MCBS, was defined as a grade A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. For ASCO-VF and OLUtool clinical benefit was defined as score ≥45 and A or B, respectively. Concordance between the frameworks was calculated with Cohen's Kappa (κ). Factors associated with clinical benefit were evaluated by logistic regression. Results In the study period, 48 drugs were approved for 92 evaluable indications, based on 100 studies. Ratings for ESMO-MCBS, ASCO-VF and OLUtool could be performed for 100, 86, and 97 studies, respectively. Overall, 39 (39%), 44 (51%), 45 (46%) of the studies showed substantial clinical benefit according to ESMO-MCBS v1.1, ASCO-VF, OLUtool criteria, respectively. There was fair concordance between ESMO-MCBS and ASCO-VF in the palliative setting (κ = 0.31, P = 0.004) and moderate concordance between ESMO-MCBS and OLUtool (κ = 0.41, P<0.001). There was no significant concordance between ASCO-VF and OLUtool (κ = 0.18, P = 0.12). Factors associated with substantial clinical benefit in multivariable analysis were HRQoL benefit reported as secondary outcome for ESMO-MCBS and the ASCO-VF and blinded studies for OLUtool. Conclusions At the time of approval, only around half of the trials supporting marketing authorisation of recently approved cancer drugs in Switzerland meet the criteria for substantial clinical benefit when evaluated with ESMO-MCBS, ASCO-VF or OLUtool. There was at best only moderate concordance between the grading systems
Clinical Benefit and Expedited Approval of Cancer Drugs in the United States, European Union, Switzerland, Japan, Canada, and Australia
We studied all new cancer drugs approved in the six aforementioned jurisdictions from 2007 to 2020. We extracted all applicable expedited programs, total regulatory review times, and, for drugs first approved by the FDA, times to subsequent regulatory approval. Clinical benefit was assessed using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale value framework and ASCO-Cancer Research Committee's targets. Nonparametric Kruskal-Wallis test was used to compare total review times for high versus low clinical benefit drugs. One hundred and twenty eight drugs received initial approval in at least one of the six included jurisdictions. Most drugs approved by the FDA (91%) and Health Canada (59%) qualified for at least one expedited program within those jurisdictions, compared with 46% of EMA approvals and 18% of PMDA approvals. The FDA was the first regulator to approve 102 (80%) drugs. Delays in submission accounted for a median of 20.2% (EMA) to 83.8% (PMDA) of the time to subsequent approval. There was no association between high clinical benefit and shorter total review times. Most new cancer therapies were approved first by the FDA, and delays in submission of regulatory applications accounted for substantial delays in approving cancer drugs in other countries. Regulators should prioritize faster review for drugs with high clinical benefit
Association between control group therapy and magnitude of clinical benefit of cancer drugs
Little is known about the impact of control group therapy on clinical benefit scales such as American Society of Clinical Oncology Value Framework (ASCO-VF), European Society for Medical Oncology Magnitude Clinical Benefit Scale (ESMO-MCBS), National Comprehensive Cancer Network (NCCN) Evidence Blocks and ASCO Cancer Research Committee (ASCO-CRC). We searched Drugs@FDA to identify cancer drugs approved between January 2012 and December 2021 based on randomized trials (RCTs). Definition of substantial clinical benefit was based on recommendations for each scale. Associations between characteristics of control group therapy and clinical benefit were explored using logistic regression. RCTs with a control group of active treatment plus placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = 0.003) and ASCO-VF (OR 0.30, P = 0.008) but not with NCCN Evidence Blocks or ASCO-CRC. This effect was attenuated and lost statistical significance without adjustment for quality of life (QoL) and/or toxicity (ESMO-MCBS OR 0.50, P = 0.17; ASCO-VF OR 0.49, P = 0.11). Clinical benefit scales can be sensitive to control group therapy. RCTs with substantial overlap between experimental and control therapy showed lower magnitude of clinical benefit using ESMO-MCBS and ASCO-VF scales; possibly due to differences in the weighting of QoL and toxicity between different frameworks
Electronic health records and patient registries in medical oncology departments in Spain
We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain. This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM. We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department. Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes. Not applicable The online version contains supplementary material available at 10.1007/s12094-021-02614-9
Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer : patient-reported outcomes from the FLIPPER trial
In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2− advanced breast cancer (ABC). We assessed health-related quality of life (QoL) using patient-reported outcomes (PROs). In this phase II double-blinded study, PROs were assessed at baseline after every three cycles and at the end of the treatment using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23. Time to deterioration (TTD) in global health status (GHS)/QoL was defined as a decrease of ⩾10 points. Changes from baseline (CFB) and TTD were analysed using linear mixed-effect and Cox regression models, respectively. Of the 189 randomised (1:1) patients, 178 (94%) completed ⩾1 post-baseline assessment; 50% received ⩾22 cycles of study treatment, with a questionnaire compliance >90%. Mean baseline scores were comparable between arms. GHS/QoL scores were maintained throughout the palbociclib/fulvestrant treatment. CFB showed significant differences for GHS/QoL, appetite loss, constipation and systemic therapy side effect scores favouring placebo/fulvestrant. TTD in GHS/QoL was delayed in placebo/fulvestrant versus palbociclib/fulvestrant [30.3 versus 11.1 months; adjusted hazard ratio (aHR): 1.57, 95% CI: 1.03-2.39, p = 0.036]; this difference was not significant in patients with progressive disease (aHR: 1.2, 95% CI: 0.6-2.2, p = 0.658). No statistically significant differences in TTD were found for the other QLQ-C30 and QLQ-BR23 scales. Although TTD in GHS/QoL was prolonged with placebo/fulvestrant, no differences were observed on other functional or symptom scales. This finding and the improvement in PFS support the combination of palbociclib/fulvestrant as a beneficial therapeutic option for HR+/HER2− ABC. Sponsor Study Code: GEICAM/2014-12 EudraCT Number: 2015-002437-21 ClinTrials.gov reference: NCT0269048
marcadors biològics predictius de resposta a la quimioteràpia primària (neoadjuvant) amb antraciclines i taxans
Predir la resposta a la quimioteràpia és un repte fonamental en el tractament de pacients amb càncer de mama. El benefici de la quimioteràpia amb antraciclines i taxans en càncer de mama precoç és modest i els efectes secundaris a llarg termini no desdenyables. La identificació de factors predictius de resposta permetria millorar l'eficàcia de la quimioteràpia i minimitzar les toxicitats secundàries. Actualment no disposem de biomarcadors específics per predir la resposta del tumor a la quimioteràpia amb antraciclines i taxans.
L’amplificació del gen Human epidermal growth factor receptor 2 (HER2), la topoisomerasa II alfa (TOP2A) i la duplicació del centròmer del cromosoma 17 (CEP17) s’han proposats com a biomarcadors predictius de resposta a les antraciclines mentre que una expressió disminuïda de la proteïna Tau i dels isotips I a IV de la β-tubulina s’han relacionat amb la resposta a la quimioteràpia amb taxans. Els resultats dels estudis són discordants i cap d’aquests biomarcadors tumorals pot ser considerat un marcador predictiu de resposta a les antraciclines i taxans.
En el present estudi s’han analizat aquests potencials marcadors predictius de resposta al tractament en una cohort de 140 pacients amb càncer de mama estadis II i III tractades amb quimioteràpia neoadjuvant amb antraciclines i taxans, emprant la resposta completa patològica com a marcador subrogat de quimiosensibilitat. Posteriorment s'ha avaluat el seu impacte en la supervivència.
Els resultats d’aquesta tesi demostren: que la duplicació del CEP17 prediu la resposta completa patològica en pacients amb càncer de mama tractades amb esquemes de quimioteràpia basades en antraciclines, i que la baixa expressió de la proteïna Tau s’associa a la resposta a la quimioteràpia neoadjuvant i al benefici amb taxans. Les pacients amb alta expressió de la proteïna Tau tenen millor pronòstic.Predicting response to chemotherapy is a central challenge in treating patients with breast cancer. Anthracycline–taxane-based chemotherapy produces a modest improvement in survival for women with early-stage breast cancer. However, these drugs are associated with serious side-effects and careful selection is needed to ensure that they are given only to patients who may benefit from them. To date, no specific biomarkers have been identified to predict tumor response to anthracycline-taxane-based chemotherapy.
Human epidermal growth factor receptor 2 (HER2), topoisomerase II alpha (TOP2A) genes and chromosome 17 centromere enumeration probe (CEP17) duplication have all been proposed as predictive biomarkers of anthracycline treatment, whereas low expression of the microtubule-associated protein Tau and classes I to IV β-tubulin isotypes has been linked to better response to taxane chemotherapy. However, reports are conflicting, and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracycline–taxane-based chemotherapy.
We studied the predictive and prognostic value of TOP2A gene alterations, HER2 gene amplification, CEP17 duplication and Tau protein expression, as well as classes I to IV β-tubulin isotypes expression in 140 patients with operable or locally advanced breast cancer receiving anthracycline-taxane-based neoadjuvant chemotherapy.
The results of this thesis show that: CEP17 duplication predicts pathologic complete response to primary anthracycline-based chemotherapy, and low Tau protein expression is associated with response to neoadjuvant chemotherapy and taxane benefit. Patients with high Tau expression have a better prognosis
marcadors biològics predictius de resposta a la quimioteràpia primària (neoadjuvant) amb antraciclines i taxans
Predir la resposta a la quimioteràpia és un repte fonamental en el tractament de pacients amb càncer de mama. El benefici de la quimioteràpia amb antraciclines i taxans en càncer de mama precoç és modest i els efectes secundaris a llarg termini no desdenyables. La identificació de factors predictius de resposta permetria millorar l'eficàcia de la quimioteràpia i minimitzar les toxicitats secundàries. Actualment no disposem de biomarcadors específics per predir la resposta del tumor a la quimioteràpia amb antraciclines i taxans.
L’amplificació del gen Human epidermal growth factor receptor 2 (HER2), la topoisomerasa II alfa (TOP2A) i la duplicació del centròmer del cromosoma 17 (CEP17) s’han proposats com a biomarcadors predictius de resposta a les antraciclines mentre que una expressió disminuïda de la proteïna Tau i dels isotips I a IV de la β-tubulina s’han relacionat amb la resposta a la quimioteràpia amb taxans. Els resultats dels estudis són discordants i cap d’aquests biomarcadors tumorals pot ser considerat un marcador predictiu de resposta a les antraciclines i taxans.
En el present estudi s’han analizat aquests potencials marcadors predictius de resposta al tractament en una cohort de 140 pacients amb càncer de mama estadis II i III tractades amb quimioteràpia neoadjuvant amb antraciclines i taxans, emprant la resposta completa patològica com a marcador subrogat de quimiosensibilitat. Posteriorment s'ha avaluat el seu impacte en la supervivència.
Els resultats d’aquesta tesi demostren: que la duplicació del CEP17 prediu la resposta completa patològica en pacients amb càncer de mama tractades amb esquemes de quimioteràpia basades en antraciclines, i que la baixa expressió de la proteïna Tau s’associa a la resposta a la quimioteràpia neoadjuvant i al benefici amb taxans. Les pacients amb alta expressió de la proteïna Tau tenen millor pronòstic.Predicting response to chemotherapy is a central challenge in treating patients with breast cancer. Anthracycline–taxane-based chemotherapy produces a modest improvement in survival for women with early-stage breast cancer. However, these drugs are associated with serious side-effects and careful selection is needed to ensure that they are given only to patients who may benefit from them. To date, no specific biomarkers have been identified to predict tumor response to anthracycline-taxane-based chemotherapy.
Human epidermal growth factor receptor 2 (HER2), topoisomerase II alpha (TOP2A) genes and chromosome 17 centromere enumeration probe (CEP17) duplication have all been proposed as predictive biomarkers of anthracycline treatment, whereas low expression of the microtubule-associated protein Tau and classes I to IV β-tubulin isotypes has been linked to better response to taxane chemotherapy. However, reports are conflicting, and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracycline–taxane-based chemotherapy.
We studied the predictive and prognostic value of TOP2A gene alterations, HER2 gene amplification, CEP17 duplication and Tau protein expression, as well as classes I to IV β-tubulin isotypes expression in 140 patients with operable or locally advanced breast cancer receiving anthracycline-taxane-based neoadjuvant chemotherapy.
The results of this thesis show that: CEP17 duplication predicts pathologic complete response to primary anthracycline-based chemotherapy, and low Tau protein expression is associated with response to neoadjuvant chemotherapy and taxane benefit. Patients with high Tau expression have a better prognosis
Marcadors biològics predictius de resposta a la quimioteràpia primària (neoadjuvant) amb antraciclines i taxans
Predir la resposta a la quimioteràpia és un repte fonamental en el tractament de pacients amb càncer de mama. El benefici de la quimioteràpia amb antraciclines i taxans en càncer de mama precoç és modest i els efectes secundaris a llarg termini no desdenyables. La identificació de factors predictius de resposta permetria millorar l'eficàcia de la quimioteràpia i minimitzar les toxicitats secundàries. Actualment no disposem de biomarcadors específics per predir la resposta del tumor a la quimioteràpia amb antraciclines i taxans. L'amplificació del gen Human epidermal growth factor receptor 2 (HER2), la topoisomerasa II alfa (TOP2A) i la duplicació del centròmer del cromosoma 17 (CEP17) s'han proposats com a biomarcadors predictius de resposta a les antraciclines mentre que una expressió disminuïda de la proteïna Tau i dels isotips I a IV de la β-tubulina s'han relacionat amb la resposta a la quimioteràpia amb taxans. Els resultats dels estudis són discordants i cap d'aquests biomarcadors tumorals pot ser considerat un marcador predictiu de resposta a les antraciclines i taxans. En el present estudi s'han analizat aquests potencials marcadors predictius de resposta al tractament en una cohort de 140 pacients amb càncer de mama estadis II i III tractades amb quimioteràpia neoadjuvant amb antraciclines i taxans, emprant la resposta completa patològica com a marcador subrogat de quimiosensibilitat. Posteriorment s'ha avaluat el seu impacte en la supervivència. Els resultats d'aquesta tesi demostren: que la duplicació del CEP17 prediu la resposta completa patològica en pacients amb càncer de mama tractades amb esquemes de quimioteràpia basades en antraciclines, i que la baixa expressió de la proteïna Tau s'associa a la resposta a la quimioteràpia neoadjuvant i al benefici amb taxans. Les pacients amb alta expressió de la proteïna Tau tenen millor pronòstic.Predicting response to chemotherapy is a central challenge in treating patients with breast cancer. Anthracycline-taxane-based chemotherapy produces a modest improvement in survival for women with early-stage breast cancer. However, these drugs are associated with serious side-effects and careful selection is needed to ensure that they are given only to patients who may benefit from them. To date, no specific biomarkers have been identified to predict tumor response to anthracycline-taxane-based chemotherapy. Human epidermal growth factor receptor 2 (HER2), topoisomerase II alpha (TOP2A) genes and chromosome 17 centromere enumeration probe (CEP17) duplication have all been proposed as predictive biomarkers of anthracycline treatment, whereas low expression of the microtubule-associated protein Tau and classes I to IV β-tubulin isotypes has been linked to better response to taxane chemotherapy. However, reports are conflicting, and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracycline-taxane-based chemotherapy. We studied the predictive and prognostic value of TOP2A gene alterations, HER2 gene amplification, CEP17 duplication and Tau protein expression, as well as classes I to IV β-tubulin isotypes expression in 140 patients with operable or locally advanced breast cancer receiving anthracycline-taxane-based neoadjuvant chemotherapy. The results of this thesis show that: CEP17 duplication predicts pathologic complete response to primary anthracycline-based chemotherapy, and low Tau protein expression is associated with response to neoadjuvant chemotherapy and taxane benefit. Patients with high Tau expression have a better prognosis
Clinical benefit and prices of cancer drugs in the United States and Europe
Background: Given rising cancer drug costs, Medicare recently proposed to tie some US drug prices to average prices paid by comparable countries. To understand the potential scope of this policy, we assessed differences in cancer drug prices in the US and selected European countries. We also evaluated the correlation between drug prices and their clinical benefit, as measured by two value frameworks: the American Society of Clinical Oncology Value Framework v2 (ASCO VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale v1.1 (ESMO-MCBS). Methods: We identified all new drugs for adult solid and hematologic cancers, approved by the FDA from 2009-2017 and that have also been approved by the EMA by December 31, 2018. US average sales prices (and if not available, wholesale acquisition costs) were extracted as of February 1, 2019, and compared to comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland. ASCO VF and ESMO-MCBS scores were assessed for pivotal trials supporting solid tumor drugs; in case of multiple trials, we focused on the highest score. Consistent with the developers of the rating scales, “high benefit” was defined as scores of A-B (neo/adjuvant setting) and 4-5 (palliative setting) on the ESMO-MCBS scale and scores≥45 on the ASCO VF. Linear regression models and non-parametric Kruskal-Wallis test and were used to assess the association between drug prices and benefit scores. Results: The study cohort included 63 drugs approved by the FDA and the EMA during the study period. 46 (73%) were approved for solid tumors, and 17 (27%) were approved for hematologic malignancies. Overall, median cancer drug prices in included European countries were 52% (interquartile range: 37-72%) lower than US prices. There was no statistically significant association between monthly treatment cost and ASCO-VF or ESMO-MCBS scores in any country. There was also no association between price differential between US and median European drug prices and either ASCO-VF (P = 0.599) or ESMO-MBCS (P = 0.321) scores. Conclusions: Cancer drug prices in the US were significantly higher than in the compared European countries. Drug prices of cancer drugs were not associated with clinical benefit in the US or in European countries
Treatment with anticancer drugs for advanced pancreatic cancer : a systematic review
Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes. We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach. We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status. The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care. The online version contains supplementary material available at 10.1186/s12885-023-11207-4