Abstract
Introduction
Ipilimumab plus nivolumab has been approved for intermediate- and poor-risk metastatic
renal cell carcinoma (RCC). However, the activity in non–clear cell RCC (nccRCC) is
unknown.
Patients and Methods
Patients from Cleveland Clinic and the University of Texas Southwestern who had received
ipilimumab plus nivolumab for metastatic nccRCC from October 2017 to May 2019 were
retrospectively identified. Ipilimumab plus nivolumab was administered in accordance
with the CHECKMATE 214 trial. Imaging was obtained at baseline and every 12 weeks.
The baseline patient characteristics, objective response per Response Evaluation Criteria
in Solid Tumors, version 1.1, and treatment-related adverse events (TRAEs) per Common
Terminology Criteria for Adverse Events, version 5.0, were analyzed.
Results
Eighteen patients were identified. The median age was 59 years (range, 32-81 years),
77.8% were men, and the Eastern Cooperative Oncology Group performance status was
0 (38%) or 1 (50%). The median treatment duration was 2.4 months (range, 0.7-12.3
months). The non–clear cell histologic types included 6 papillary, 5 chromophobe,
3 unclassified, 2 adenocarcinoma of renal origin, 1 translocation, and 1 medullary.
Most had an intermediate (66%) or poor (22%) International Metastatic Database Consortium
risk. The best objective response included 6 partial responses (PRs; 33.3%) and 3
with stable disease (16.7%). Of the patients with a PR, the median time to the best
response was 3.0 months, and median duration of the PR was 4.3 months. The median
progression-free survival was 7.1 months. All-grade TRAEs were noted in 11 patients
(61.1%) and included colitis (22%), hepatotoxicity (16%), rash (11%), and fatigue
(11%). Eleven patients (61%) had TRAEs requiring high-dose glucocorticoids (> 40 mg
of prednisone equivalent daily).
Conclusions
Ipilimumab plus nivolumab demonstrated objective responses and notable toxicity in
patients with nccRCC.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Genitourinary CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.Int J Cancer. 2015; 136: E359-E386
- Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.Lancet. 2011; 378: 1931-1939
- Nivolumab versus everolimus in advanced renal-cell carcinoma.N Engl J Med. 2015; 373: 1803-1813
- Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.N Engl J Med. 2018; 378: 1277-1290
- Non-clear cell renal cell carcinomas: from shadow to light [e-pub ahead of print]. J Clin Oncol.(accessed)https://doi.org/10.1200/JCO.2018.79.2531(accessed October 1, 2019)
- The 2016 WHO classification of tumours of the urinary system and male genital organs—part A: renal, penile, and testicular tumours.Eur Urol. 2016; 70: 93-105
- Systemic therapy for non-clear cell renal cell carcinomas: a systematic review and meta-analysis.Eur Urol. 2015; 67: 740-749
- Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: characterization of survival outcome and application of the International mRCC database consortium criteria.Cancer. 2013; 119: 2999-3006
- Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.Lancet Oncol. 2016; 17: 378-388
- Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (ESPN): a randomized multicenter phase 2 trial.Eur Urol. 2016; 69: 866-874
- Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC.Ann Oncol. 2017; 28: 1339-1345
- PD-L1 expression in nonclear-cell renal cell carcinoma.Ann Oncol. 2014; 25: 2178-2184
- Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma.J Immunother Cancer. 2018; 6: 9
- Thirty-month follow-up of the phase III CheckMate 214 trial of first-line nivolumab+ ipilimumab (N+ I) or sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).J Clin Oncol. 2019; 37: 547
- The clinical activity of PD-1/PD-L1 inhibitors in metastatic non-clear cell renal cell carcinoma.Cancer Immunol Res. 2018; 6: 758-765
- Nivolumab for the treatment of patients with metastatic non-clear cell renal cell carcinoma (nccRCC): a single-institutional experience and literature meta-analysis [e-pub ahead of print]. Oncologist.https://doi.org/10.1634/theoncologist.2019-0372(accessed October 1, 2019)
- First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): results from KEYNOTE-427 cohort B.J Clin Oncol. 2019; 37: 546
- A phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO).J Clin Oncol. 2019; 37: 545
- Atezolizumab plus bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (ccRCCsd): updated results of activity and predictive biomarkers from a phase II study.J Clin Oncol. 2019; 37: 4583
Article info
Publication history
Published online: December 04, 2019
Accepted:
November 27,
2019
Received in revised form:
November 26,
2019
Received:
October 4,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
