Both late and early phase immune checkpoint inhibitor (CPI) combination trials indicate an impending role of combinations in the first-line treatment of metastatic renal cell carcinoma (mRCC). Sequencing the options following failure of CPI combinations is an emerging conundrum. Objective: To present our single-center clinical experience with targeted therapies (TT) following first-line CPI combinations. Methods: mRCC patients who received TT following failure of a combination regimen with CPI

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... ere identified from an institutional database. Clinical information including tumor characteristics, survival outcomes, and adverse events was retrieved from medical records. Descriptive statistics and Kaplan-Meier survival functions were performed. Results: Of 11 patients identified, median age was 63 (31-79) and 8 (73%) patients were male. First-line treatment was a CPI and TT combination in 7 (64%) patients while the rest received combination of two CPIs. The majority of patients (82%) were intermediate risk category at the initiation of targeted therapies. TTs utilized included cabozantinib (46%), lenvatinib and everolimus (27%), sunitinib (18%), and temsirolimus (9%). Best response was stable disease for 10 (91%) and partial response for 1 (9%) patient. In a median follow up of 9.1 months (range, 4.9-34.1), median progression free survival was 7.7 (95% CI 4.6-10.8) months. Progression has occurred in 7 patients, and 3 patients remain on treatment. One patient discontinued treatment due to toxicity. Conclusions: In our report, TTs demonstrate effective disease control and safety. Further exploration in prospective setting is warranted.