Disentangling the reasons why older adults do not readily participate in cancer trials: a socio-epidemiological mixed methods approach.

BACKGROUND: Few studies of the under-representation of older adults in cancer clinical trials (CTs) have encompassed the entire pathway from a trial being available in a cancer centre to the patient's invitation to participate and then agreement or refusal to participate. OBJECTIVES: The study's primary objective was to evaluate CT non-invitation and refusal rates. The secondary objectives were to identify factors associated with non-invitation and refusal and to assess experiences of CT participation from the patients' and professionals' perspectives. METHODS: Here, we used mixed methods and a socio-epidemiological approach to analyse reasons for the non-participation of eligible older patients with a solid cancer in cancer CTs in France. RESULTS: We found that non-invitation and low CT participation are mainly related to the patients' sociodemographic characteristics and living conditions (such as social isolation, being single, divorced or widowed, not having children and the absence of close family members) and the healthcare professionals' perceptions of insufficient informal support or a high homecare requirement. CONCLUSION: Our results suggest that efforts to increase fair inclusion and the participation of older adults in CTs should target the physician-patient relationship, the medical profession and hospital funding, rather than the patient alone.

[Epidemiology of cancer in the elderly in France]. / Épidémiologie du cancer chez la personne âgée en France.

In the population aged 65 and over, there were 233 943 new cases of cancer in 2015 in France. For those aged 85 and over, the incidence was 41 947 new cases of cancer (10.6% of all cancer cases). In 2015, there were 112 596 deaths specifically related to cancer of people aged over 65 (55.6% of whom were men), representing 75.3% of all deaths from cancer.

Antibody drug conjugates in older patients: State of the art.

More than half of cancer cases occur in patients aged 65 years or older. The efficacy and safety of antibody drug conjugates (ADCs) in older patients remains an unclear subject as available evidence is limited. Geriatric population is underrepresented in clinical trials. Consequently, most of our knowledge regarding innovative therapeutics was studied on a younger population. In this review of published literature, we report the available information on efficacy, safety and pharmacokinetics of FDA approved ADCs for hematologic malignancies and solid tumors in the geriatric population. We explore the results of clinical trials dedicated for older individuals as well as subgroup analyses of the geriatric population in major trials evaluating these drugs. Available data suggest a similar efficacy in older adults as compared to general population. However, older patients might be prone to a higher rate of adverse events in incidence with a potential impact on quality of life. We lack data to support primary dose reductions or schedule modifications in this category of patients. No pharmacokinetic differences were reported between age groups. It is crucial to encourage the development of clinical trials dedicated to older patients with geriatric parameters (G8 score, G-CODE…) so that results can be more representative of this population outside of clinical trials.

Enrolment of older adults with advanced or metastatic non-small cell lung cancer in first-line clinical trials in the multicentre ESME cohort.

INTRODUCTION: There is a great need for data based on clinical trials for the older population in order to improve treatment. Historically, the inclusion rate of older adults in clinical trials has been low, but the rate specific to lung cancer is unknown, as are the factors associated with enrolment. MATERIALS AND METHODS: We used the national Epidemio-Strategy and Medical Economics Advanced or Metastatic Lung Cancer (AMLC) Data Platform, a multicentre real-life database. Inclusion criteria were patients with advanced or metastatic non-small cell lung cancer (AMNSCLC) aged 70 years or older, with at least one line of systemic treatment from 01 January 2015 to 31 December 2018. The primary objective was to evaluate the proportion of older adults enrolled in clinical trials. Secondary objectives were to identify factors associated with enrolment in clinical trials for older patients and to compare the overall survival of older adults included in trials versus those not included. RESULTS: There were 3488 patients aged ≥70 years (median age at AMNSCLC 75 years). Among older patients, 234 (6.7%) were enrolled in a clinical trial in the first-line setting. Significant factors associated with enrolment in the multivariable analysis in older patients were: good Eastern Cooperative Oncology Group (ECOG) Performance Status (PS 0) (p < 0.001), de novo versus recurrent presentation at diagnosis (p < 0.001), and non-central nervous system (CNS) metastases versus advanced setting or CNS metastases (p < 0.001). Medical history was associated with fewer inclusions (odds ratio [OR] = 0.74, 95% confidence interval [CI] [0.56; 0.99]). Among older patients, being enrolled in a trial in the first-line setting was not associated with better overall survival (OS) (hazard ratio [HR] = 1.03; 95%CI 0.86-1.22) in the multivariable analysis. DISCUSSION: In this large database, few older AMNSCLC patients were enrolled in a trial. Factors associated with enrolment were: good ECOG PS, absence of medical history, de novo AMNSCLC, and presentation with non-CNS metastases.

Prevalence of Four Sarcopenia Criteria in Older Patients with Cancer, and Their Predictive Value for 6-Month Mortality: The NutriAgeCancer National Prospective Cohort Study.

Older cancer patients have an elevated risk of sarcopenia. The aim was to estimate the prevalence of four criteria for sarcopenia case finding, assessment, diagnosis, and severity determination: abnormal strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F), low hand-grip strength (HGS), low arm circumference (AC, a muscle mass proxy), and low physical performance (PP). Sarcopenia (low HGS and AC) and severe sarcopenia (low HGS, AC, and PP) and their predictive values for 6-month mortality were estimated in the whole population and by metastatic status. We analyzed data from the NutriAgeCancer French nationwide study of cancer patients aged ≥70 referred for geriatric assessment before anti-cancer treatment. We performed Cox proportional hazards analysis for each criterion separately and all criteria combined. Overall, 781 patients from 41 geriatric oncology clinics were included (mean age: 83.1; females: 53%; main cancer types: digestive (29%) and breast (17%); metastases: 42%). The prevalence of abnormal SARC-F, low HGS, a low AC, low PP, sarcopenia, and severe sarcopenia were, respectively, 35.5%, 44.6%, 44.7%, 35.2%, 24.5%, and 11.7%. An abnormal SARC-F and/or low HGS, sarcopenia, and severe sarcopenia were associated with 6-month mortality in patients with metastases (adjusted hazard ratios [95% confidence interval]: 2.72 [1.34-5.49], 3.16 [1.48-6.75] and 6.41 [2.5-16.5], respectively). Sarcopenia was strongly predictive of 6-month mortality in patients with metastatic cancer.

Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis.

OBJECTIVES: We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients. STUDY DESIGN AND SETTING: We included cancer patients aged ≥70 years from the Elderly Cancer Patients cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on the one hand and mortality on the other. RESULTS: The analysis included 1,434 patients (mean age: 80 ± 5.6 years; women: 48%; main cancer sites: digestive tract [36.2%], urinary tract and prostate [26.6%], and breast [16.5%]; metastatic cancer: 48%). Direct relationships to 6- and 12-month mortality were identified for functional impairment (standardized coefficient [SC]: 0.37 [P < 0.001] and 0.32 [P < 0.001], respectively), poor nutritional status (SC: 0.11 [P = 0.005] and 0.14 [P = 0.001]), poor social support (SC = 0.07 [P = 0.08] and 0.09 [P = 0.02]), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment, and depression on mortality were mediated by functional and nutritional status. CONCLUSION: In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality.

Chemotherapy and gene expression profiling in older early luminal breast cancer patients: An International Society of Geriatric Oncology systematic review.

BACKGROUND: The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We summarise evidence on efficacy, safety, and quality-of-life impacts of chemotherapy and on GEP use and impact in older HR-positive, HER2-negative EBC patients. METHODS: We conducted a literature search of PubMed and Embase on publications describing prospective studies evaluating chemotherapy in older adults with HR-positive, HER2-negative EBC and on publications describing retrospective and prospective studies evaluating GEP in older adults. RESULTS: Eight publications on chemotherapy use, including 2,035 older patients with EBC were selected. Only one trial evaluated chemotherapy survival benefits in older adults, showing no benefit. Of four studies comparing different regimens, only one showed the superiority of taxanes versus anthracyclines alone. Those investigating alternative regimens did not show improvements over standard regimens despite significant limitations. Five publications on GEP, including 445,323 older patients, were included and investigated Oncotype DX. Limited evidence shows that GEP aids treatment decisions in this population. GEP was offered less frequently to older versus younger patients. Higher Recurrence Score was prognostic for distant recurrence, but chemotherapy did not improve prognosis. CONCLUSIONS: In older patients with HR-positive, HER2-negative, chemotherapy survival benefits EBC are unclear and GEP is less used. Although its prognostic role is well established, its predictive role remains unknown.

[Why and how to assess older people with cancer?] / Pourquoi et comment évaluer les sujets âgés atteints de cancer ?

The older population accounts for almost 60% of new cancers. Their management is a public health problem and is complex. It raises different questions: Is the patient's prognosis linked to cancer or another pathology? The heterogeneity of this population emphasises the importance of the overall condition assessment, in particular to avoid over-treatment (or under-treatment), and to be able to identify frail or vulnerable elderly patients who are at risk of having more treatment toxicities. Through this article, we will recall the importance of geriatric in-depth evaluation (EGA) by detailing the different factors that impact the therapeutic decision, tolerance to treatments… This EGA is however time-consuming and not all patients can be evaluated. In order to identify the subjects covered by this EGA, screening scales have been developed. Finally, we will develop the place of research in oncogeriatric management.

Complications and Discharge after Radical Cystectomy for Older Patients with Muscle-Invasive Bladder Cancer: The ELCAPA-27 Cohort Study.

Radical cystectomy is the standard of care for localized bladder cancer but is associated with high morbidity and mortality rates-especially among older patients with comorbidities. The association between geriatric assessment parameters on post-operative complications and discharge has not previously been investigated. The present analysis of the Elderly Cancer Patient (ELCAPA) prospective cohort included all patients aged ≥70 having undergone a geriatric assessment and then radical cystectomy for localized muscle-invasive bladder cancer between 2007 and 2018. The primary endpoint was the proportion of patients with one or more complications in the first 30 days after cystectomy. The secondary endpoints were the length of hospital stay (LOS), the 30-day mortality, and discharge rates. Sixty-two patients (median age: 81; range: 79-83.8) were included. The 30-day complication rate was 73%, and 49% of the patients had experienced a major complication, according to the Clavien-Dindo classification. The 30-day mortality rate was 4%. None of the geriatric, oncological, or laboratory parameters were significantly associated with the occurrence or severity of complications. The median (interquartile range) LOS was 18 days (15-23) overall and was longer in patients with complications (19 days vs. 15 days in those without complications; p = 0.013). Thirty days after cystectomy, 25 patients (53%) had been discharged to home and 22 (47%) were still in a rehabilitation unit. In a univariate analysis, a Geriatric-8 score ≤ 14, a loss of one point on the Activities of Daily Living Scale, anemia, at least one grade ≥ 3 comorbidity on the Cumulative Illness Rating Scale-Geriatric, and an inpatient geriatric assessment were associated with a risk of not being discharged to home. In older patients having undergone a geriatric assessment, radical cystectomy is associated with a high complication rate, a longer LOS, and functional decline at 30 days.

Biomarker Testing in Older Patients Treated for an Advanced or Metastatic Non-Squamous Non-Small-Cell Lung Cancer: The French ESME Real-Life Multicenter Cohort Experience.

BACKGROUND: Genomic and immunologic tumor biomarker testing has dramatically changed the prognosis of patients, particularly those treated for advanced/metastatic non-squamous non-small-cell lung cancer (aNSCLC) when access to targeted agents is available. It remains unclear whether older patients have access to therapy-predictive biomarker testing techniques in the same proportion as younger patients. This study aims to compare the proportion of biomarker testing performed in non-squamous aNSCLC at diagnosis between patients aged ≥70 years old and their younger counterparts. METHODS: We conducted a retrospective analysis using the Epidemio-Strategy and Medical Economics (ESME) Advanced or Metastatic Lung Cancer Data Platform, a French multicenter real-life database. All patients with non-squamous aNSCLC diagnosed between 2015 and 2018 were selected. Biomarker testing corresponded to at least one molecular alteration and/or PD-L1 testing performed within 1 month before or 3 months after the aNSCLC diagnosis. RESULTS: In total, 2848 patients aged ≥70 years and 6900 patients aged <70 years were included. Most patients were male. The proportion of current smokers at diagnosis was higher in the <70 years group (42% vs. 17%, p < 0.0001). There was no significant difference in the proportion of biomarker testing performed between the two groups (63% vs. 65%, p = 0.15). EGFR mutations were significantly more common in the older group (22% vs. 12%, p < 0.0001) and KRAS mutations significantly more frequent in the younger group (39% vs. 31% p < 0.0001). The distribution of other driver mutations (ALK, ROS1, BRAF V600E, HER2, and MET) was similar across age. In the multivariable analysis, factors independently associated with biomarker testing were gender, smoking status, history of COPD, stage at primary diagnosis, and histological type. CONCLUSIONS: Age is not a barrier to biomarker testing in patients with aNSCLC.

Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts.

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.

Perspectives on cancer care in older patients in France.

In France, cancer is the leading cause of death. Its incidence is increasing due to the growing population and longer life expectancy. Although older adults represent most new cases, they remain underrepresented in clinical trials. Their prognosis is often worse due to delayed diagnosis and multimorbidities. Geriatric oncology has made great strides worldwide, highlighted by important studies implementing geriatric assessment in clinical research and supported by the successive national cancer plans. This paper reviews the most important actions taken in France during the last decade to improve the management of older patients with cancer.