As older adults with cancer are underrepresented in randomized clinical trials (RCT), there is limited evidence on which to rely for treatment decisions for this population. Commonly used RCT endpoints for the assessment of treatment efficacy are more often tumor-centered (e.g., progression-free survival). These endpoints may not be as relevant for the older patients who present more often with comorbidities, non-cancer-related deaths, and treatment toxicity. Moreover, their expectation and preferences are likely to differ from younger adults.

The DATECAN-ELDERLY initiative combines a broad expertise, in geriatric oncology and clinical research, with interest in cancer RCT that include older patients with cancer. In order to guide researchers and clinicians coordinating cancer RCT involving older patients with cancer, the experts reviewed the literature on relevant domains to assess using patient-reported outcomes (PRO) and patient-related outcomes, as well as available tools related to these domains.

Domains considered relevant by the panel of experts when assessing treatment efficacy in RCT for older patients with cancer included functional autonomy, cognition, depression and nutrition. These were based on published guidelines from international societies and from regulatory authorities as well as minimum datasets recommended to collect in RCT including older adults with cancer. In addition, health-related quality of life, patients' symptoms, and satisfaction were also considered by the panel. With regards to tools for the assessment of these domains, we highlighted that each tool has its own strengths and limitations, and very few had been validated in older adults with cancer. Further studies are thus needed to validate these tools in this specific population and define the minimum clinically important difference to use when developing RCTs in this

In cancer randomized controlled trials (RCT), the validated and most objectively defined evaluation criterion is overall survival (OS - delay between randomization and death). Therapeutic progress, the current context of strategic trials, and the multiplication of lines of treatment have resulted in the necessity to identify evaluation criteria other than OS, which can be observed more frequently and sooner. Endpoints such as progression-free survival (PFS) or disease-free survival (DFS) are commonly used instead of OS in RCT. The priority for patients, however, is to live longer or better, and ideally both, which raises the question as to the suitability of these tumor-specific endpoints to assess the benefit/risk balance associated to a new therapy in elderly patients with cancer. Older patients may die from causes other than cancer, and relapse does not necessarily shorten survival. Instead, cancer therapy can sometimes cause severe acute or chronic toxicities and affect functional status or health-related quality of life (HRQoL), and as such these patient-centered outcomes (e.g. autonomy, quality of life) should be given more attention. On the basis of these considerations, OS may not be the most appropriate outcome to measure treatment benefit in the elderly cancer population.

Geriatric oncology experts and task forces including the International Society of Geriatric Oncology, the European Organization for Research and Treatment Cancer (EORTC) and the DIALOG research group (Dialogue Intergroupe pour la personnALisation de la prise en charge en OncoGériatrie), have acknowledged the heterogeneity of primary endpoints used in RCT conducted in elderly cancer patients. This heterogeneity, in terms of dimension (tumor-centered outcomes, patient-centered outcomes including autonomy, nutrition, etc.) and definitions limits the comparison of results across trials. In addition, this can make the design of trials particularly complex since estimation of sample size is usually based on results from past trials. Acknowledging the specificities of the elderly population, the DATECAN-Elderly project is aimed at providing guidelines for the definition of efficacy endpoints that will permit to assess new treatments/interventions in this population.

The DATECAN-Elderly project is a continuation of the development of guidelines within the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials). This international initiative was launched in 2009 to elaborate standardized definitions for survival endpoints in RCT, based on a rigorous and validated consensus methodology. This work has resulted in the publication of guidelines to define time-to-event endpoints to be used in randomized trials for specific cancer sites: sarcomas, pancreas, breast, and other. These guidelines however were not developed for the elderly cancer patients. Events specifically accounted for included exclusively tumor-oriented events (e.g. local, regional, metastatic progressions, or deaths due to various causes).

DATECAN-Elderly guidelines will be developed in cooperation with many experts in the field of geriatric oncology and clinical trials from different scientific backgrounds (medical oncologists, geriatricians, biostatisticians, etc.) and groups/societies (DIALOG, SIOG, EORTC, etc.), favouring the acceptability of the resulting recommendations. R

Results of the DATECAN-Elderly project are expected to address the heterogeneity regarding efficacy endpoints used as primary endpoints in elderly cancer trials. Providing definitions for endpoints should lead to the evaluation of treatment more consistent with patient's experiences and expectations about treatment outcome. Overall, the project should help provide trials' results which are more relevant for the elderly patients, improves the recruitment of elderly patient in RCT, and finally enhance trials' comparison and design.

Inclusion Criteria:

• Elderly patients with cancer

Exclusion Criteria:

• Individual patient data unavailable

No patient will be included.

14 experts participated in the panel

All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed.

All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed.