Clinical Experience in Treating ccRCC (Patient Case 1)
Panelists discuss the challenges of managing intermediate-risk metastatic clear cell renal cell carcinoma (ccRCC) after progression on first-line immunotherapy (IO)/tyrosine kinase inhibitor (TKI) therapy, emphasizing cabozantinib’s role, individualized dosing strategies, proactive toxicity management, and the importance of patient-centered care to optimize long-term disease control and quality of life.
This case highlights the complexity of managing a patient with intermediate-risk metastatic ccRCC following progression on a first-line IO/TKI regimen. After achieving an initial partial response and stable disease for more than 1 year on axitinib plus pembrolizumab, the patient now presents with new hepatic lesions and pulmonary progression. Given her good performance status, minimal toxicity on prior therapy, and desire for an aggressive approach focused on long-term disease control, second-line treatment must balance efficacy with tolerability.
In such scenarios, cabozantinib is a commonly favored option due to its activity in VEGF-refractory disease and tolerability profile. Experience shows that although some patients can maintain full dosing at 60 mg, many require early dose adjustments due to adverse effects. Strategies to improve adherence and minimize interruptions include preemptive education on expected toxicities, early follow-ups, nurse navigator involvement, and flexible monitoring. Individualized management plans, such as dose interruptions or modified schedules (eg, 5 days on/2 days off), are used to optimize dose intensity without compromising quality of life.
Real-world data underscore that only about half of patients proceed to second-line therapy, making first-line treatment duration critical. However, when transition to second line occurs, maintaining continuity through clear communication, anticipatory guidance, and proactive symptom management is key. Long-term management is further supported by imaging surveillance every 3 months, selective brain imaging, and attention to cumulative toxicities such as proteinuria. Ultimately, patient-centric, flexible dosing strategies combined with aggressive but thoughtful sequencing of therapies are essential to prolong disease control and preserve quality of life in patients with advanced ccRCC.
