Management of Colorectal Cancer in Older Adults

Immunotherapy

Between 3.5% and 6.5% of stage IV colorectal cancers are MSI-H and have deficient mismatch repair (dMMR).^99–101 A recent phase 2 trial studied the use of pembrolizumab, an IgG4 monoclonal antibody against PD-1 (programmed cell death-1), in heavily pretreated patients with dMMR metastatic CRC, MMR-proficient (pMMR) metastatic CRC, and noncolorectal dMMR metastatic cancer.¹⁰² Patients with dMMR metastatic CRC had a 50% ORR and 89% disease control rate (DCR), as compared with an ORR of 0% and DCR of 16% in patients with pMMR metastatic CRC. There was also an OS and PFS benefit seen in the dMMR CRC group as compared with the pMMR CRC group. Another phase 2 study, CheckMate 142, studied the anti-PD-1 monoclonal antibody nivolumab with or without ipilimumab (a monoclonal antibody against cytotoxic T-lymphocyte antigen 4) in patients with dMMR and pMMR metastatic CRC.¹⁰³ In the interim analysis, nivolumab was found to provide both disease control and durable response in patients with dMMR metastatic CRC.

While these studies led to the FDA approval of pembrolizumab and nivolumab for management of previously treated MSI-H or dMMR metastatic CRC, data on the use of immunotherapy in older adults is scarce. Immunosenescence, or the gradual deterioration of the immune system that comes with aging, may impact the efficacy of immune checkpoint inhibitors (ICI) in older patients with advanced cancer.¹⁰⁴ There is conflicting data on the efficacy of PD-1 and programmed death ligand-1) PD-L1 inhibitors in older patients across different cancers. A meta-analysis of immunotherapy in older adults with a variety of malignancies showed overall efficacy comparable to that seen in adults younger than 65 years.¹⁰⁵ However, another review found ICIs to be less effective in older patients with head and neck, non-small cell lung cancer, and renal cell carcinoma compared with their younger counterparts.¹⁰⁴ Regarding the toxicity profile of ICIs in the elderly, similar rates of grade 3 or higher adverse events in patients younger than 65 years and older than 65 years have been reported.¹⁰⁶ However, patients aged ≥ 70 years had increased rates of grade 3 to 5 adverse events as compared to patients younger than 65 years (71.7% versus 58.4%, respectively). Given the scant data on ICIs in older patients with MSI-H or dMMR metastatic CRC, more clinical trials inclusive of this population are needed in order to determine the efficacy and safety of immunotherapy.

Palliative Care

The incorporation of palliative care early following the diagnosis of cancer has been shown to improve quality of life, decrease depression, and help with symptom management.¹⁰⁷ The triggers for geriatric patients to initiate palliative care may be different from those of younger patients, as older patients may have different goals of care.¹⁰⁸ Older patients will often choose quality over quantity of life when making treatment decisions.¹⁰⁹ The ideal medical treatment for the frail patient with colorectal cancer would focus on treating disease while providing palliative measures to help support the patient and improve quality of life. It is paramount that patients maintain functional independence as loss of independence is recognized as a major threat to an older patient’s quality of life.¹¹⁰ The optimal way to achieve these goals is through the efforts of a multidisciplinary care team including not only physicians and nurses, but also social workers, nutritionists, physical therapists, and family who can provide support for the patient’s psychosocial, cognitive, and medical needs.¹¹¹ Although cancer and noncancer–related death occur more frequently in the geriatric population, data to guide a specific palliative care approach to the elderly population is lacking.¹⁰⁸