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
4614 - Predictors of Response to Checkpoint Inhibitors in Naïve and Ipilimumab-Refractory Melanoma
Presenter: Domenico Mallardo
Session: Poster Display session 3
Resources:
Abstract
2901 - IFN-γ/IL-10 ratio as predictive biomarker for response to anti-PD-1 therapy in metastatic melanoma patients
Presenter: Emilio Giunta
Session: Poster Display session 3
Resources:
Abstract
2306 - Multiplex Chromogenic Immunohistochemistry (IHC) for Spatial Analysis of Checkpoint-Positive Tumor Infiltrating Lymphocytes (TILs)
Presenter: Scott Ely
Session: Poster Display session 3
Resources:
Abstract
1678 - The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: a meta-analysis of randomized clinical trials.
Presenter: Alberto Carretero-Gonzalez
Session: Poster Display session 3
Resources:
Abstract
5138 - Radiomic Features as a Non-invasive Biomarker to Predict Response to Immunotherapy in Recurrent or Metastatic Urothelial Carcinoma
Presenter: Kye Jin Park
Session: Poster Display session 3
Resources:
Abstract
5800 - Integrative combination of high-plex digital profiling techniques and cluster analysis to reveal complex immune biology in the tumor microenvironment of mesothelioma
Presenter: Carmen Ballesteros-Merino
Session: Poster Display session 3
Resources:
Abstract
5736 - Predictive factors of response to immunotherapy in 198 patients with metastatic non-microcytic lung cancer (mNSCLC): real world data from 2 university hospitals in Spain
Presenter: Juan Felipe Cordoba Ortega
Session: Poster Display session 3
Resources:
Abstract
5645 - Evaluating Lung CT Density Changes Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Treated with Thoracic Radiotherapy (TRT) alone or TRT Followed by Combined Ipilimumab (IPI) and Nivolumab (NIVO).
Presenter: Kujtim Latifi
Session: Poster Display session 3
Resources:
Abstract
1540 - Immuno-oncology therapy biomarkers differences between polyoma-virus positive and negative Merkel cell carcinomas
Presenter: Zoran Gatalica
Session: Poster Display session 3
Resources:
Abstract
4538 - Can we improve patient selection for phase 1 clinical trials (Ph1) based on Immuno-Oncology score prognostic index (VIO)?
Presenter: Ignacio Matos Garcia
Session: Poster Display session 3
Resources:
Abstract