2613 - Lenvatinib (Len) alone or in combination with Everolimus (Eve) in heavily pretreated patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitors (ICI) and VEGFR-targeted therapies: A single-institution experience

Background

ICI and VEGFR-targeted therapies are the primary treatments for mRCC. Len plus Eve is currently approved based on improved progression-free survival (PFS) in pts with progressive disease after one prior VEGFR-targeted therapy. However, its efficacy beyond second-line, and after ICI, is not well defined.

Methods

We conducted a retrospective study of pts with mRCC who were treated with Len alone, or in combination with Eve, after at least 2 prior lines of therapy, including ICI and VEGFR-TKI. We report clinical benefit (CB), defined as partial response (PR) + stable disease (SD), PFS, overall survival (OS), and adverse events (AE).

Results

Between 11/2016 and 2/2019, we identified 40 pts with mRCC who were treated with Len +/- Eve. Median age was 59 years (range, 34-76); 62.5% were male; 52.5% had ECOG PS 1 and 35% had ECOG PS 2; 77.5% had clear cell histology; 85% had prior nephrectomy and 95% had metastatic disease in >/= 3 sites; 2.5% had IMDC favorable-risk, 87.5% intermediate-risk, and 10% poor-risk disease. The median number of prior lines of therapy was 4 (range, 2-10); 70% received Len+Eve and 62.5% were treated with Len +/- Eve as 5th-line or later. All pts had prior ICI exposure, primarily nivolumab monotherapy (70%), and 87.5% received >/= 2 prior VEGFR-TKIs. CB was achieved in 67.5% (30% PR + 37.5% SD). At a median follow up of 8.5 months (mo), median PFS was 4.2 mo (95% CI, 3.4-6.5), with a 6-mo PFS probability of 34% (95% CI, 21%-54%). Median OS was 10.8 mo (95% CI, 5.4-13.3), with a 1-year OS probability of 37% (95% CI, 21%-65%). Twenty-three pts (57.5%) have died, and of those only 4 received further therapies after Len +/- Eve. Dose reduction was required in 45% of pts, and the most common grade 3 or 4 AEs were proteinuria (17.5%), fatigue (10%), and diarrhea (10%). Treatment was discontinued in 4 pts (10%) because of toxicity.

Conclusions

Len alone and in combination with Eve demonstrated clinical benefit, with an overall response rate of 30%, and was well tolerated in heavily pretreated pts with mRCC after prior ICI and VEGFR-targeted therapies, supporting its use in this patient population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

Z. Lim: Speaker Bureau / Expert testimony: Exelixis. M.T. Campbell: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), non-branded educational programs: EMD Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), non-branded educational programs: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Apricity Health; Research grant / Funding (self): Exelixis; Research grant / Funding (self): Janssen; Speaker Bureau / Expert testimony, non-branded educational programs: Bristol-Meyers Squibb; Speaker Bureau / Expert testimony, non-branded educational programs: Roche; Speaker Bureau / Expert testimony, non-branded educational programs: Merck. A.Y. Shah: Honoraria (self), Research grant / Funding (self): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): EMD Serono. A. Zurita Saavedra: Speaker Bureau / Expert testimony: McKesson Specialty Health; Speaker Bureau / Expert testimony: Janssen-Cilag, S.A.DEC.V.; Advisory / Consultancy: Incyte; Advisory / Consultancy: Pfizer. E. Jonasch: Advisory / Consultancy, Research grant / Funding (self): Exelixis; Advisory / Consultancy, Research grant / Funding (self): Novartis; Research grant / Funding (self): Peloton; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Roche. N.M. Tannir: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Calithera Biosciences Inc.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai Medical Research; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy, Travel / Accommodation / Expenses: Oncorena; Research grant / Funding (self): Epizyme; Research grant / Funding (self): Mirati Therapeutics. All other authors have declared no conflicts of interest.