First-line RCC Systemic Therapy Following Adjuvant Immunotherapy

Patients with renal cell carcinoma (RCC) who experience disease recurrence on or after adjuvant immunotherapy (IO) benefit from subsequent systemic therapies across different regimens, according to a new study being presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Adjuvant pembrolizumab is approved by the US Food and Drug Administration for the adjuvant treatment of RCC. Further research is needed on sequential treatments following recurrence after pembrolizumab or other IO-based therapies administered in the adjuvant setting.

Talal El Zarif, MD, of Yale University School of Medicine, and colleagues designed an international multicenter study to better understand the benefit of systemic therapy following adjuvant pembrolizumab in these patients. They included 144 patients from 27 institutions who received adjuvant IO-based systemic RCC therapies. The safety and efficacy of subsequent systemic therapy regimens that included vascular endothelial growth factor (VEGF)-targeted therapies or alternative IO-based therapies were evaluated.

Researchers used the Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS) from the time of systemic therapy initiation following adjuvant IO. Objective response rates (ORRs) were determined per Response Evaluation Criteria in Solid Tumors v1.1 criteria, and treatment-related adverse events (TRAEs) leading to treatment discontinuation, dose reduction, or steroid use were noted.

Dr. El Zarif and colleagues observed that most patients had clear cell disease (90%), underwent radical nephrectomy (94%), and had high- or intermediate-high-risk disease (90%) per KEYNOTE-564 risk groups. Additionally, they reported that most patients received adjuvant pembrolizumab (51%), atezolizumab (28%), or nivolumab plus ipilimumab (11%).

Adjuvant IO cessation occurred due to treatment completion (45%), recurrence (25%), or toxicity (24%).

No disease recurrence was found in 36% of patients who remained under observation. Following recurrence, 75% of patients received systemic therapy, while the remaining 25% underwent surgery or radiotherapy.

After a median follow-up of 16.7 months, Dr. El Zarif and colleagues reported a PFS of 16.0 months (95% CI, 10.4-41.7). The 18-month OS was 86% (95% CI, 76.4%-97.3%), and the ORR was 36%.

Most patients received VEGF-targeted therapy (46%), IO/VEGF combination therapy (30%), or single or combination IO therapy (17%). ORRs were comparable across these treatment groups (35%, 45%, and 42%, respectively).

TRAEs occurred in 41% of patients treated with subsequent systemic therapy.

“Patients with RCC who recur on or after adjuvant IO treatment benefit from subsequent systemic therapies across different regimens,” study authors concluded.