How to Balance Treatment Risk, Benefit in Older Patients With Cancer

In 2012 alone, there were an estimated 6.7 million new cases of cancer were diagnosed in adults aged 65 years or older, with that number expected to double by 2035.^1,2 However, there is a paucity of evidence to guide treatment in this population.

One reason for the lack of data for this population is that older adults are currently underrepresented in clinical trials. Between 1993 and 1996, patients 65 years and over accounted for 25% of participants in SWOG trials; however, they constituted 63% of the population of patients with cancer in the United States during that same period.

Another reason there may be less evidence for this population is that older patients with cancer are often treated less aggressively, inadequately, or not at all, irrespective of comorbidities. The cause may be related to patients’ intolerance to treatment, or potentially due to physician or patient biases about agerelated tolerance.³

For oncology pharmacists, the question is: How do we balance the benefits and risks of treating older patients with cancer? Oncologists often use the ECOG or Karnofsky performance status scales to assess functional level and ability to tolerate therapy. Geriatricians use a more age-specific, global assessment of function and general health to assess patient status and potential disease and treatment outcomes.

Specifically, geriatricians employ the Comprehensive Geriatric Assessment (CGA), a multidisciplinary, in-depth evaluation of objective health in the older adult using 8 domains that affect cancer prognosis, treatment choice, and tolerance: function, comorbidities, support, cognition, psychology or emotion, nutrition, polypharmacy, and geriatric syndromes (TABLE). Especially when there is apprehension about a patient’s ability to tolerate treatment, the National Comprehensive Cancer Network Older Adult Oncology Panel recommends pretreatment evaluation with the CGA.¹

Generally, pharmacists play a key role in the polypharmacy portion of the CGA, which includes a medication review and adherence assessment, as well as the management of adverse effects. Polypharmacy, often defined as taking 5 or more medications, is associated with drug interactions. For instance, in a retrospective analysis of 244 patients over the age of 70 years, investigators assessed the impact of potential drug interactions (PDIs) and their association with chemotherapy intolerance. They identified 82 PDIs that translated to a doubling of severe nonhematological toxicities with each PDI, and a tripling if the PDI involved chemotherapy.⁴

Medication reviews of existing prescription and OTC medications are conducted prior to initiation or change in treatment, change in comorbid disease management, or change in clinical condition as determined by the clinical team. The process for a comprehensive medication review is described abundantly in the literature.⁵

Pharmacists can also assess objective chemotherapy risk using the Cancer and Aging Research Group (CARG) Chemo-Toxicity Calculator or the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score.^6-8 CARG has been validated for patients aged 65 and older and CRASH for those 70 and older. CARG is easier to use; it is quick and estimates the risk of grade 3, 4, and 5 toxicity.⁷ CRASH separates grade 3 hematologic toxicity and nonhematologic toxicity, incorporates other screenings, and can be considered a complete geriatric assessment in and of itself. The choice to use CRASH or CARG depends on the team’s workflow.⁸ If the pharmacist is zeroing in on chemotherapy risk and assessing how to adjust the dose, CARG may be the better option; if completing a full geriatric assessment, CRASH may be better suited. Both are free to use.

When patients have a deficiency in a CGA domain or a high CARG or CRASH score, it is critical to evaluate the literature and guidelines. It may be necessary to reduce the dose or regimen and intervene to provide education, referrals, and support.

About the Author

Jerline Hsin, PharmD, BCPS, BCOP, is a clinical pharmacist specialist at City of Hope and a member of the editorial advisory board of Pharmacy Times Oncology Edition.

References

1. NCCN. Clinical Practice Guidelines in Oncology. Older adult oncology, version 1.2023. Accessed March 8, 2023. https://www.nccn.org/guidelines/guidelines-detail?category=4&id=1452

2. Pilleron S, Sarfati D, Janssen-Heijnen M, et al. Global cancer incidence in older adults, 2012 and 2035: a population-based study. Int J Cancer. 2019;144:49-58. doi:10.1002/ijc.31664

3. Luciani A, Bertuzzi C, Ascione G, et al. Dose intensity correlate with survival in elderly patients treated with chemotherapy for advanced non-small cell lung cancer. Lung Cancer. 2009;66(1):94-96. doi:10.1016/j.lungcan.2008.12.019

4. Popa MA, Wallace KJ, Brunello A, Extermann M, Balducci L. Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy. J Geriatr Oncol. 2014;5(3):307-314. doi:10.1016/j.jgo.2014.04.002

5. Hoel RW, Giddings Connolly RM, Takahashi PY. Polypharmacy management in older patients. Mayo Clin Proc. 2021:96(1):242-256. doi:10.1016/j.mayocp.2020.06.012

6. Mohile SG, Mohamed MR, Xu H, et al. Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study. Lancet. 2021;398(10314):1894-1904. doi:10.1016/S0140-6736(21)01789-X

7. Chemo-toxicity calculator. Cancer and Aging Research Group. Accessed February 15, 2023. https://www.mycarg.org/?page_id=2405

8. CRASH score form. Moffitt Cancer Center. Accessed February 15, 2023. https://moffitt.org/eforms/crashscoreform