ICI therapy is an established strategy in mRCC after progressive disease on VEGFR-TKI. Little data exists in the reverse sequence on response rate, progression-free survival (PFS), safety, and tolerability of TKI after 1L ICI therapy.
This is a retrospective analysis of patients with mRCC treated from 2015 to present with 1L ICI, followed by 2L TKI. Response assessment was provided by a blinded radiologist using RECIST 1.1. Descriptive statistics, Fisher’s test and Wilcoxon rank sum test were used.
We report on 27 clear-cell mRCC patients with follow-up of at least 8 weeks on TKI post 1L ICI. Median age at diagnosis was 58 years. 78% of patients had lung, 37% bone, 37% lymph node, and 7% liver metastasis. As 1L therapy, 7 patients received nivolumab, 17 received nivolumab + ipilimumab, and 3 received nivolumab + bevacizumab. All 27 patients had resolution of Grade 3/4 toxicities from ICI and progressive disease at the time of TKI initiation. Median time from discontinuation of ICI to initiation of TKI was 4.1 weeks (range 0-23.3 weeks). 11 patients (41%) had PR (8 of whom had ≥40% tumor reduction), and 16 (59%) had SD as best response to TKI. Median PFS was 10.0 months (95% CI 6.8, not applicable). 9 patients discontinued 2L TKI after a median of 26.3 weeks (range 4.6-44 weeks), 8 patients because of PD and 1 because of toxicity. 2 patients developed Grade 3 transaminitis and 3 patients Grade 3 hand-foot skin reaction. Age, sex, IMDC risk score, nephrectomy status, and TKI agent did not predict PR or SD.Table:
|Variable||Total n (%)||PR (n)||SD (n)||P value|
|Localized at presentation||9 (33)||7||2||0.01|
|Metastatic at Presentation||18 (67)||4||14|
|IMDC good risk||4 (15)||3||1||0.47|
|IMDC intermediate risk||19 (70)||7||12|
|IMDC poor risk||4 (15)||1||3|
|Primary in-situ||6 (22)||1||5|
In this small retrospective study, we observed a high response rate (41%), median PFS 10 months, and manageable toxicity in patients with mRCC treated with TKI after ICI. No patients had outright PD on 2L TKI after ICI.
Clinical trial identification
Not applicable (retrospective study)
Legal entity responsible for the study
MD Anderson Cancer Center Dept of Genitourinary Medical Oncology
G. Jianjun: Travel/Honoraria & Consulting: AstraZeneca. M.T. Campbell: Consulting/advisory role: AstraZeneca, Eisai. A. Zurita Saavedra: Research support: Pfizer. E. Jonasch: Research funding: Exelixis, Pfizer, Novartis Honoraria: Bristol-Myers Squib, Eisai, Exelixis, Novartis, Pfizer. P. Sharma: Stock: Jounce, Kite Pharma, Evelo, Neon & Constellation Consulting/advisory role: Bristol-Myers Squib, GSK, AstraZeneca, Amgen, Constellation, Jounce, Kite Pharma, Evelo, Neon & EMC Serono Patents (spouse): Jounce, Merck, Bristol-Myers Squib. N. Tannir: Travel/Honoraria & Consulting: Bristol-Myers Squib, Exelixis, Nektar, Novartis, Pfizer, Argos, Calithera Research: Bristol-Myers Squib, Exelixis, Epizyme, Novartis, Miranti. All other authors have declared no conflicts of interest.