Managing Safety and Adverse Events in Practice

Managing Safety and Adverse Events in Practice

The overall survival findings from KEYNOTE-B61 are validated by analysis of subsequent therapy patterns, which demonstrate that patients received appropriate standard-of-care treatments following progression. Among the 61% of patients who received subsequent therapy, the most common treatments were VEGF receptor inhibition, followed by mTOR inhibition and checkpoint inhibitor therapy. This treatment paradigm reflects real-world clinical practice, where patients who progress after first-line immunotherapy plus TKI combination typically receive another VEGF receptor inhibitor as second-line therapy. The appropriate use of subsequent therapies supports the validity of the impressive overall survival results observed in the study.

The safety profile of pembrolizumab plus lenvatinib showed that while the vast majority of patients experienced some adverse events, the toxicity pattern was manageable and consistent with expectations for this combination. Grade 3 or 4 adverse events occurred in 77% of patients, with 31% of patients experiencing adverse events leading to treatment discontinuation, and 26% having treatment-related adverse events requiring therapy cessation. These discontinuation rates align with real-world clinical practice, where approximately 20% to 25% of patients typically discontinue combination immunotherapy plus TKI due to toxicity. The similarity between trial and practice rates suggests the study population represents a realistic patient cohort.

Clinical management of toxicities requires careful differentiation between TKI-related and immunotherapy-related adverse events, particularly for overlapping toxicities such as diarrhea and elevated liver function tests. The most common treatment-related adverse events occurring in at least 15% of patients included hypertension, diarrhea, and hypothyroidism—typical chronic TKI toxicities. Effective management strategies emphasize patient education using 3 key principles: understanding, identifying, and reporting adverse events early. This proactive approach includes comprehensive patient education in clinic, specialized classes, nursing education during infusion, frequent checkups, and remote monitoring tools such as blood pressure tracking through patient portals. Early identification and prompt management of adverse events, particularly immunotherapy-related toxicities, prevents progression from acute to severe or chronic complications.