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Nivolumab for metastatic renal cell carcinoma (mRCC): Results of a randomized, dose-ranging phase II trial.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, restores T-cell immune activity and showed objective responses in mRCC in a phase I trial (NEJM 366:2443). This phase II trial (NCT01354431) assesses three nivolumab doses in mRCC patients (pts) pretreated with agents targeting the VEGF pathway. Methods: Pts with clear-cell mRCC (≥1 agent targeting VEGF pathway; ≤3 prior systemic therapies) were randomized (blinded 1:1:1) to nivolumab 0.3, 2 or 10 mg/kg IV Q3W until progression or toxicity. The primary objective was to evaluate the dose-response relationship measured by progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR) and safety assessment. Results: All pts (N=168) received prior systemic therapy (70% received ≥2) including VEGFR TKIs (98%), mTOR inhibitors (38%) and immunotherapy (24%). 25% were MSKCC poor risk. All had >16 months of follow-up. No dose-response relationship was noted for PFS (stratified trend test, P=0.9). PFS and ORR were similar across doses (Table). For 0.3 mg/kg, median duration of response was 15.7 months and median OS was 18.2 months; for other doses medians were not reached. Across doses 19/35 responders (54%) had objective responses lasting >12–20+ months. Rates of grade 3–4 related adverse events (AEs) were ≤17% for all doses (Table). There was no grade 3–4 pneumonitis. For 0.3, 2 and 10 mg/kg, 1 (2%), 6 (11%) and 4 (7%) pts, respectively, had treatment-related AEs that led to discontinuation. Conclusions: Antitumor activity was observed with nivolumab in this pretreated mRCC population including objective responses of long duration. No dose-response relationship for PFS was noted and the safety profile was acceptable. Median OS was 18.2 months for the 0.3 mg/kg dose and was not reached for 2 or 10 mg/kg; updated OS will be presented. Clinical trial information: NCT01354431.
|Median PFS, months (80% CI)||2.7 (1.9, 3.0)||4.0 (2.8, 4.2)||4.2 (2.8, 5.5)|
|ORR, n (%)||12 (20)||12 (22)||11 (20)|
|Median OS, months (80% CI)||18.2 (16.7, NR)||NR||NR|
|Treatment-related AE, n (%)
a Safety analysis included 59 treated pts; CI=confidence interval; NR=not reached.
Abstracts by Robert J. Motzer:
Analysis of real-world treatment adherence in a cohort of 2,395 patients with metastatic renal cell carcinoma (mRCC).Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 517
CheckMate 025 phase III trial: Outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC).Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 498
Differential overall survival (OS) results in RECORD-3 study based on three distinct mRCC molecular subgroups classified by BAP1 and/or PBRM1 mutations.Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 561
Presentations by Robert J. Motzer:
Genome-wide association study (GWAS) of efficacy and safety endpoints in pazopanib- or sunitinib-treated patients with renal cell carcinoma (RCC).Meeting: 2014 ASCO Annual Meeting Abstract No: 4503Session: Genitourinary (Nonprostate) Cancer (Oral Abstract Session)