Ethical considerations in the relief of cancer pain.

The management of pain for patients with cancer and cancer survivors is a critical clinical task that involves a multitude of ethical issues at almost every phase of the cancer experience. This review is divided into three sections: In the first, we address rights and duties in the relief of pain from the perspective of patients, clinicians, health care institutions and organizations, and public policy. This section includes a detailed description of issues and duties in relation to opioid misuse and addiction. In the second section, we discuss the ethical consideration of therapeutic planning. The final section addresses ethical considerations in the management of pain at the end of life including a detailed discussion regarding ethical issues relating to the use of palliative sedation as a clinical intervention of last resort.

Feasibility of Large-Scale Implementation of an Electronic Patient-Reported Outcome Remote Monitoring System for Patients on Active Treatment at a Community Cancer Center.

PURPOSE: The use of digital symptom monitoring with patient-reported outcomes (PROs) has been shown to improve patient outcomes. The evidence of benefit has been largely derived from research studies. The feasibility of adopting this technology in the real-world setting is unknown. METHODS: We report on the clinical implementation of a proprietary electronic patient-reported outcome (ePRO)-based digital symptom monitoring platform at the Highlands Oncology Group practice, a large community oncology practice. We present here our experience with patient enrollment, engagement, and retention; reasons for discontinued use; proportion of reports generating alerts and containing severe symptoms; and the responses to alerts including nursing telephone consultations and urgent office visits. RESULTS: Over an approximately 17-month period, 923 patients were successfully enrolled. Patients enrolled from June 20, 2020, through November 30, 2021, with follow-up through February 28, 2022. Retention rates at 3, 6, 9, and 12 months were 94%, 88%, 73%, and 67%, respectively, with greater retention at 12 months in patients age 65 years or older. Few patients discontinued use for reasons related to the platform (n = 47; 5%). Of the 25,311 ePRO reports submitted, 49% (n = 12,334) exceeded the predefined alert thresholds and 8% (n = 1,920) included severe symptoms. The nursing team responded within 24 hours by telephone to 31.2% (n = 3,910) of all reports with alerts. Of reports with severe symptoms, 72.7% (n = 1,395) received a call. Only 6.4% (n = 249) of phone calls required an office evaluation within 72 hours of the report. CONCLUSION: This single-center experience indicates that an ePRO-based digital symptom monitoring platform can be effectively implemented at a large scale with a high level of long-term patient engagement. Most reports could be effectively resolved by nurses, and physician intervention was infrequently required.

An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed?

In 2016, the then US President Barack Obama announced the Cancer Moonshot with a view to making 10 years' worth of progress in cancer prevention, diagnosis and treatment in only 5 years. This Perspective evaluates the FDA approvals of therapeutic agents for use in solid tumour oncology for the period 2017-2021 against the aspirations of the Cancer Moonshot. In the past 5 years, the FDA issued an unprecedented 161 new approvals of therapeutic agents for various indications in adult patients with solid tumours. However, less than a third (27%) of the newly approved medicines are supported by unequivocal evidence of an overall survival benefit; most are supported by positive signals from surrogate end points. Herein, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 was used to evaluate the clinical value of the therapies granted FDA approval during the period 2017-2021. The results of this appraisal indicate a low level of clinical benefit for a substantial proportion (~20%) of the new indications, with most (~44%) providing intermediate benefit. The data suggest that, beyond increases in the sheer quantity of approvals, considerable improvement in the quality of the approved treatments is required to more confidently ensure that the clinical benefits are real and substantial enough to clearly justify the risks to patients.

Lessons learnt from scoring adjuvant colon cancer trials and meta-analyses using the ESMO-Magnitude of Clinical Benefit Scale V.1.1.

Click here to listen to the Podcast BACKGROUND: Form 1 of the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) serves to grade therapies with curative intent. Hitherto only few trials with curative intent have been field tested using form 1. We aimed to evaluate the applicability of the scale and to assess the reasonableness of the generated scores in early colon cancer, in order to identify shortcomings that may be rectified in future amendments. METHODS: Adjuvant studies were identified in PubMed, Food and Drug Administration and European Medicines Agency registration sites, as well as ESMO and National Comprehensive Cancer Network guidelines. Studies meeting inclusion criteria were graded using form 1 of the ESMO-MCBS V.1.1 and field tested by ESMO Colorectal Cancer Faculty. Shortcomings of the scale were identified and evaluated. RESULTS: Eighteen of 57 trials and 7 out of 14 meta-analyses identified met criteria for ESMO-MCBS V.1.1 grading. In stage III colon cancer, randomised clinical trials and meta-analyses of modulated 5-fluorouracil (5-FU) based chemotherapy versus surgery scored ESMO-MCBS grade A and randomised controlled trials (RCTs) and meta-analyses comprising oxaliplatin added to this 5-FU backbone showed a more modest additional overall survival benefit (grade A and B). For stage II colon cancer, the findings are less consistent. The fluoropyrimidine trials in stage II were graded 'no evaluable benefit' but the most recent meta-analysis demonstrated a 5.4% survival advantage after 8 years follow-up (grade A). RCTs and a meta-analysis adding oxaliplatin demonstrated no added benefit. Exploratory toxicity evaluation and annotation was problematic given inconsistent toxicity reporting and limited results of late toxicity. Field testers (n=37) reviewed the scores, 25 confirmed their reasonableness, 12 found them mostly reasonable. Moreover, they identified the inability of crediting improved convenience in non-inferiority trials as a shortcoming. CONCLUSION: Form 1 of the ESMO-MCBS V.1.1 provided very reasonable grading for adjuvant colon cancer studies.

Application of the ESMO-Magnitude of Clinical Benefit Scale (V.1.1) to the field of early breast cancer therapies.

Click here to listen to the Podcast BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated value scale for solid tumour anticancer treatments. Form 1 of the ESMO-MCBS, used to grade therapies with curative intent including adjuvant therapies, has only been evaluated for a limited number of studies. This is the first large-scale field testing in early breast cancer to assess the applicability of the scale to this data set and the reasonableness of derived scores and to identify any shortcomings to be addressed in future modifications of the scale. METHOD: Representative key studies and meta-analyses of the major modalities of adjuvant systemic therapy of breast cancer were identified for each of the major clinical scenarios (HER2-positive, HER2-negative, endocrine-responsive) and were graded with form 1 of the ESMO-MCBS. These generated scores were reviewed by a panel of experts for reasonableness. Shortcomings and issues related to the application of the scale and interpretation of results were identified and critically evaluated. RESULTS: Sixty-five studies were eligible for evaluation: 59 individual studies and 6 meta-analyses. These studies incorporated 101 therapeutic comparisons, 61 of which were scorable. Review of the generated scores indicated that, with few exceptions, they generally reflected contemporary standards of practice. Six shortcomings were identified related to grading based on disease-free survival (DFS), lack of information regarding acute and long-term toxicity and an inability to grade single-arm de-escalation scales. CONCLUSIONS: Form 1 of the ESMO-MCBS is a robust tool for the evaluation of the magnitude of benefit studies in early breast cancer. The scale can be further improved by addressing issues related to grading based on DFS, annotating grades with information regarding acute and long-term toxicity and developing an approach to grade single-arm de-escalation studies.

EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies.

OBJECTIVE: Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). METHODS: Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies. RESULTS: In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described. CONCLUSIONS: Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials.

Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?

This review article is an overview of the session at the European Society for Medical Oncology (ESMO) Asia 2018 Congress entitled: 'Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?'. The article provides an overview of the session speakers' views on the impact that the lack of accessibility and availability of medicines has on patient outcomes in the treatment of breast cancer, colorectal cancer and lung cancer, responsible for more than one-third of cancer deaths in the Asian region. It also lists the various global policy initiatives that ESMO supports to promote the best cancer care in the Asian and Asia-Pacific region. The review presents extrapolated data from the 'ESMO International Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in countries outside of Europe', which reveals several disparities among Asian countries, across the different income levels. In low- and middle-income countries, some barriers to the accessibility of anticancer medicines include the lack of government reimbursement, budget allocation for healthcare and quality-assured generic and biosimilar medicines, as well as shortages and patent rights. Throughout the article, the session presenters provide their views on strategies that can be considered to overcome these barriers.

Comparative Assessment of Clinical Benefit Using the ESMO-Magnitude of Clinical Benefit Scale Version 1.1 and the ASCO Value Framework Net Health Benefit Score.

PURPOSE: To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies. METHODS: The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance. RESULTS: The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman's rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity. CONCLUSION: The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales.

Palliative care: needs of advanced breast cancer patients.

Advanced breast cancer is characterized by many physical manifestations with the potential to undermine the quality of life (most related to the cancer and some to treatments), as well as substantial impact on psychosocial well-being. Patients with advanced breast cancer and their families have complex needs that have to be addressed in order to minimize severe distress and deterioration in the quality of life of patients and their family members. This task requires the full engagement of an interdisciplinary approach to palliative care with strong emphasis on the assessment of needs and anticipated needs, patient expectations, skilled therapeutics, and commitment to continuity of care. In this review, we address four issues: 1) organizational and conceptual issues in palliative care of patients with breast cancer, 2) common physical symptoms among patients with breast cancer and their management, 3) common psychological issues among patients with breast cancer, and 4) common challenging palliative care problems in breast cancer.

Indicators of integration at ESMO Designated Centres of Integrated Oncology and Palliative Care.

BACKGROUND: A recent international consensus panel identified 13 major indicators to assess the level of integration between oncology and palliative care. We examined these indicators among European Society for Medical Oncology (ESMO) Designated Centres (ESMO-DCs) of Integrated Oncology and Palliative Care (PC) and determined the centre characteristics associated with greater integration. METHODS: This is a preplanned secondary analysis of a recent survey to characterise the structure, processes and outcomes of the palliative care programmes at ESMO-DCs. We assessed the level of integration using 13 major indicators. We calculated two Palliative Care and Oncology Integration Indexes consisting of all 13 indicators (PCOI-13, range 0-13) and 9 of the 13 indicators (PCOI-9, range 0-9), with a higher index indicating greater integration. RESULTS: The survey response rate was 152/184 (83%). Among the 13 major indicators, interdisciplinary team was most likely to be achieved (95%), while early referral to palliative care (median time from referral to death >6 months before death) was only present in 24 (20%) of ESMO-DCs. The median PCOI-13 was 7.8 (IQR 6.4-9.6) and the median PCOI-9 was 6 (IQR 5-7). The presence of dually trained palliative oncologists was associated with higher PCOI-13 (median 8.4 vs 7.0; p=0.01) and PCOI-9 (median 6 vs 5; p=0.03). Non-tertiary hospitals generally had higher PCOI-13 (median 8.6 vs 7.2; p=0.01) and ESMO-DCs outside of Europe had higher PCOI-9 (median 7 vs 6; p=0.03). CONCLUSIONS: Assessment of the level of integration at ESMO-DCs with PCOIs highlighted strengths, areas for further development and how double-boarded palliative oncologists may promote integration.

The ESMO-Magnitude of Clinical Benefit Scale for novel oncology drugs: correspondence with three years of reimbursement decisions in Israel.

BACKGROUND: The European Society for Medical Oncology published in 2015 its Magnitude of Clinical Benefit Scale (ESMO-MCBS) for cancer medicines. Our objective was to evaluate the association between Israel's national reimbursement decisions regarding novel cancer drugs, prior to the availability of ESMO-MCBS, and the later published ESMO-MCBS scores. RESEARCH DESIGN AND METHODS: ESMO-MCBS scores were obtained retrospectively for the cancer drugs that were candidates for reimbursement in Israel in 2013-2015 and were categorized to 'highest benefit' (ESMO-MCBS 4-5 or A) 'medium benefit' (3 or B) and 'lowest benefit' (0-2 or C). The reimbursement decisions were accessed and compared with the categorized ESMO scores. RESULTS: ESMO-MCBS score was available for 19/22 drugs approved for reimbursement and 15/16 non-approved drugs. 58% of the approved drugs gained a 'highest benefit' score and 37% were 'medium benefit'. 87% of the non-approved drugs had 'lowest benefit' scores. Median score for approved drugs was 4 vs. 1 for the non-approved (p < 0.05). CONCLUSIONS: The Israeli decisions regarding reimbursement of novel cancer drugs, demonstrated concordance with ESMO-MCBS scores. Incorporation of ESMO-MCBS data in reimbursement deliberations could assist in framing the appropriate use of the limited resources to deliver effective and affordable cancer care.

Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules.

BACKGROUND: The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), a tool to assess the magnitude of clinical benefit from new cancer therapies. Grading is guided by a dual rule comparing the relative benefit (RB) and the absolute benefit (AB) achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual rule evaluates the RB of an experimental treatment based on the lower limit of the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold. This dual rule addresses two goals: inclusiveness: not unfairly penalising experimental treatments from trials designed with adequate power targeting clinically meaningful relative benefit; and discernment: penalising trials designed to detect a small inconsequential benefit. METHODS: Based on 50 000 simulations of plausible trial scenarios, the sensitivity and specificity of the LL95%CI rule and the ESMO-MCBS dual rule, the robustness of their characteristics for reasonable power and range of targeted and true HRs, are examined. The per cent acceptance of maximal preliminary grade is compared with other dual rules based on point estimate (PE) thresholds for RB. RESULTS: For particularly small or particularly large studies, the observed benefit needs to be relatively big for the ESMO-MCBS dual rule to be satisfied and the maximal grade awarded. Compared with approaches that evaluate RB using the PE thresholds, simulations demonstrate that the MCBS approach better exhibits the desired behaviour achieving the goals of both inclusiveness and discernment. CONCLUSIONS: RB assessment using the LL95%CI for HR rather than a PE threshold has two advantages: it diminishes the probability of excluding big benefit positive studies from achieving due credit and, when combined with the AB assessment, it increases the probability of downgrading a trial with a statistically significant but clinically insignificant observed benefit.