Improving Cancer Clinical Trial Participation for Older Adults

The global population is aging, leading to a significant rise in cancer incidence among older adults. By 2050, nearly 40% of new cancer cases are projected to occur in individuals aged 70 and over [1]. Despite this increasing need, older adults are consistently underrepresented in cancer clinical trials, hindering the development of treatment standards tailored to their unique needs. This underrepresentation stems from restrictive eligibility criteria, age bias, and concerns about treatment tolerance.

The Challenges of Including Older Adults in Trials

Older cancer patients often present with complexities such as multimorbidity (multiple health conditions), frailty, limited life expectancy, and a heightened risk of severe treatment toxicities. These factors, combined with logistical barriers like complex trial protocols and insufficient infrastructure, contribute to their limited participation [1]. A recent analysis revealed that only 1.5% of clinical trials registered between 2008 and 2021 included patients aged 60 and over, even when age wasn’t an explicit exclusion criterion [1].

Ethical and Scientific Implications

This lack of representation poses both ethical and scientific problems. Treatments proven effective in younger, healthier patients may not be directly transferable to older adults, whose therapeutic priorities often differ. For many, maintaining quality of life, functional independence, and cognitive function takes precedence over simply prolonging survival [1]. Clinical trials must evolve to incorporate criteria and measurable objectives that are more relevant to this population.

Strategies to Improve Participation

Experts have proposed several pragmatic strategies to address this issue. These include:

• Expanding Eligibility Criteria: Including patients with an ECOG performance status of 2 or controlled comorbidities, ensuring their safety is not compromised. Trials like GO2 and MRC-FOCUS-2 have demonstrated that adapted treatment regimens, such as dose reduction, can limit toxicities without compromising effectiveness in older patients with gastroesophageal or colorectal cancers [3].
• Integrating Geriatric Assessment: Utilizing tools like Geriatric Assessment Management (GAM) or G-Code to stratify patients based on frailty levels, personalize treatments, and improve tolerance. The ESOGIA-GFPC-GECP 08-02 trial showed that geriatric assessment-guided treatment led to fewer toxicities in older patients with non-small cell lung cancer [3].
• Adopting Innovative Trial Models: Employing pragmatic trials that reflect real-world care conditions and adaptive protocols that allow for adjustments during the study, such as therapeutic de-escalation.
• Decentralizing Trials: Utilizing telemedicine and remote monitoring to reduce geographic and logistical barriers.

Overcoming Barriers: Digital Divide, Logistics, and Ageism

Despite progress, challenges remain. The digital divide is a significant hurdle, as demonstrated by a study where 61% of elderly patients declined electronic patient-reported outcomes (PROMs) due to lack of internet access [3]. Solutions include simplified interfaces, technical support, and offering alternative data collection methods like paper questionnaires or telephone interviews. Reimbursing travel expenses, coordinating appointments, and utilizing telemedicine can alleviate logistical burdens. Addressing ageism through clinician training and awareness campaigns is also crucial [4].

The Importance of Relevant Endpoints

Traditional trial endpoints like overall survival and response rate may not fully capture the priorities of older patients. Experts recommend incorporating composite or co-primary criteria that assess tolerance, quality of life, and functional autonomy. Measuring time to functional deterioration, duration of hospitalizations, and utilizing frailty scales and cognitive assessments can provide a more comprehensive evaluation [4]. Patient-reported outcomes (PROs) are essential for assessing areas like nutrition, depression, and mobility.

Regulatory and Financial Considerations

Currently, trials focused on older adults are primarily funded by public or academic sources. Allocating budgetary supplements to centers recruiting older patients, covering costs associated with geriatric assessments, could incentivize greater inclusion. Regulatory agencies, such as the FDA, could also mandate the routine collection of geriatric data in trials involving patients aged 70 and older [4].

The FDA issued guidance in March 2022 recommending the inclusion of older adult patients in cancer clinical trials to better evaluate the benefit-risk profile of cancer drugs in this population, with particular emphasis on those over age 75 [4].

Conclusion

Including older adults in oncology clinical trials is an ethical and scientific imperative. A multidimensional approach—adapting trial designs, integrating geriatric evaluations, diversifying criteria, and removing barriers—is essential to ensure that cancer treatments are effective and appropriate for all patients, regardless of age. Initiatives like G-Code, decentralized trials, and caregiver involvement pave the way for a more inclusive and representative oncogeriatrics.