Perspectives on Treatment Choices - From Clinical Evidence to Decision-Making

In the recurrent metastatic setting, certain patient populations warrant caution when considering PD-1 inhibitors as first-line therapy. Patients with preexisting autoimmune diseases are a key group where for which careful assessment is needed. While those with well-controlled autoimmune conditions might still be candidates, the risk of immune-related adverse events and potential flares of their underlying disease is significantly higher. For patients with poorly controlled autoimmune disease, immunotherapy is generally avoided due to the high likelihood of severe toxicity, which can greatly impair quality of life or require hospitalization.

Another important group includes organ transplant recipients, especially heart transplant patients, who face a substantial risk of transplant rejection when treated with immune checkpoint inhibitors. Kidney transplant patients may have the option of dialysis as a backup, but the risk of rejection remains a serious concern across transplant types. The decision to proceed with immunotherapy in these patients requires thorough discussion weighing the potential benefits against the risks of graft loss.

Beyond specific contraindications, treatment decisions also depend on factors such as disease burden and symptomatology. For patients with moderate disease burden or elevated viral markers but minimal symptoms, starting with chemotherapy might be preferred to reduce the risk of immune-related toxicity, reserving immunotherapy for later lines. Conversely, those with aggressive, symptomatic disease may be counseled to accept the risks of immunotherapy upfront, given its potential for durable response. Additionally, for frail patients, single-agent immunotherapy may be favored over chemotherapy due to its more favorable toxicity profile and reduced impact on fatigue and overall well-being.