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J Oncol Pharm Pract. 2019 Jun 19:1078155219854797. doi: 10.1177/1078155219854797. [Epub ahead of print]

Outcomes of combination therapy with tyrosine kinase inhibitors and immune checkpoint inhibitors in metastatic renal cell carcinoma - A retrospective study.

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Yale-New Haven Hospital, New Haven, CT, USA.



Renal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor. At the time of this study, there was limited published data on the combination of tyrosine kinase inhibitors and immune checkpoint inhibitors in patients who were heavily pretreated. At our institution, providers have used these combinations in heavily pretreated patients.


We conducted a retrospective review of patients receiving this combination with the primary objectives of assessing duration of therapy and toxicities and a secondary objective of disease progression at six months. We included adult patients with confirmed mRCC receiving combination therapy (immune checkpoint inhibitors/tyrosine kinase inhibitors) any time after January 2015. Electronic medical records were reviewed for pertinent data and follow-up descriptive statistics were performed.


Fifteen patients were on combination immune checkpoint inhibitors/tyrosine kinase inhibitors, with a median of three lines of previous therapy. The median duration of combination therapy was 7.2 months (range: 0.2 to 39.8) with 126 incidences of toxicities. The most frequent toxicity was fatigue (n = 15), followed by diarrhea (n = 8), anorexia (n = 7) and palmar-plantar erythrodysesthesia (n = 7). Overall, 9 (60%) patients experienced at least one grade 3 or 4 toxicity. Eight of 15 (53%) patients remained on therapy at the six-month mark and did not have progression confirmed by an oncologist. Of the 15 patients, 10 discontinued therapy due to progression, 2 due to intolerable side effects, 2 transitioned to end of life care, and 1 patient was still ongoing at the time of data collection.


Based on this review, it appears that combination tyrosine kinase inhibitors/immune checkpoint inhibitors therapy in pre-treated patients with mRCC is tolerable and beneficial.


Combination therapy; immune checkpoint inhibitor; renal cell carcinoma; tyrosine kinase inhibitor


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