Physician Assistant Cleveland Clinic Cleveland, OH, United States
Background: Adjuvant pembrolizumab for resected RCC at high-risk for recurrence was approved in November 2021. Little is known about real world toxicity and treatment upon disease progression (PD) in this setting. We present our early experience regarding toxicity and therapy post-PD.
Methods: Patients at Cleveland Clinic treated with adjuvant pembrolizumab for high-risk ccRCC or sarcomatoid RCC were identified. Baseline and disease characteristics, risk group per KEYNOTE-564, toxicity, and post-PD treatment were collected.
Results: 20 patients were identified; median age 67 (range, 44-76), 75% male. Histology was clear cell RCC in 19 (95%), and sarcomatoid RCC without clear cell features in 1 (5%). Three (15%) patients had sarcomatoid features; 6 (30%) had rhabdoid features. T stage was pT1 (n=3; 15%) or pT3 (n=17; 85%); 3 (15%) had node-positive disease. Per KEYNOTE-564 criteria, 13 (65%) were intermediate-high risk, 3 (15%) were high-risk, and 4 (20%) were M1-NED.
Five (25%) patients completed a year of therapy and 9 (45%) are within their year of treatment. Six (30%) patients discontinued therapy prior to completing a full year, with a median time on therapy of 2.5 months (range, 1.4-10.2). Reason for discontinuation was PD (n=3) and toxicity (n=3).
Six (30%) required corticosteroids for irAEs: dermatitis (n=2), nephritis (n=1), ototoxicity (n=1), arthralgia (n=1), and polymyalgia rheumatica and elevated troponin (n=1). The ototoxicity and elevated troponin resolved rapidly with steroids, without long-term sequelae.
Of the 4 (20%) patients who developed PD on therapy, median time to PD was six months. One patient remained on therapy (underwent SRS to oligometastatic lesion) and 3 changed systemic therapy: lenvatinib/pembrolizumab (n=2) and clinical trial (n=1).
Conclusions: Adjuvant pembrolizumab is generally well-tolerated, and risk/benefit discussion is critical. Multi-center analyses are needed to determine practice patterns and outcomes for patients with disease progression on this treatment.
