Abstract 2613
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.
Resources from the same session
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract