Real‑world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma
- Authors:
- Leila Khoja
- Eshetu G. Atenafu
- Qian Ye
- Craig Gedye
- Maryanne Chappell
- David Hogg
- Marcus O. Butler
- Anthony M. Joshua
View Affiliations
Affiliations: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada
- Published online on: December 31, 2015 https://doi.org/10.3892/ol.2015.4069
-
Pages:
1581-1585
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Abstract
Approved by the Food and Drug Administration in 2011, the anti‑cytotoxic T‑lymphocyte‑associated protein 4 checkpoint inhibitor ipilimumab has delivered a survival benefit of ≥3 years in a subset of metastatic melanoma patients. After participating in the registration trial, patients were treated with this agent in routine practice. Toxicity and efficacy of agents in “real world” settings may differ from trials. The present study aimed to evaluate, with respect to toxicity and outcome, all patients treated with ipilimumab to date at the Princess Margaret Hospital (Toronto, Canada). Patients treated with ipilimumab between 2008 and 2013 were identified, and patient characteristics (age, gender, tumour burden, oncogenic mutation status, number of treatments received and toxicities from treatment) were collected. Progression‑free survival (PFS) and overall survival (OS) were calculated from the commencement of ipilimumab treatment. Associations between clinical characteristics and outcome or toxicity were assessed. Between 2008 and 2013, 129 patients with metastatic cutaneous melanoma were treated. Since, during this period, ipilimumab was approved in the second line setting, ipilimumab was delivered in the second or subsequent line in all patients, and 70% did not receive any further anticancer therapy. Immune‑related toxicities were observed, the onset of which varied from 1 to 162 days. The majority resolved within 6 weeks of the final treatment, with the exception of endocrinopathies and bowel related toxicity. The median PFS and OS were 2.83 and 8.44 months, respectively. No pre‑treatment factor independently predicted toxicity. The number of infusions (4 vs. ≤3) and presence of toxicity were significantly associated with superior survival. The onset of toxicity secondary to ipilimumab could occur later than previously reported. Toxicities were manageable, but required long‑term vigilance.
View References
1
|
Canadian Cancer Society: Canadian Cancer
Statistics. http://www.cancer.ca/en/cancer-information/cancer-101/canadian-cancer-statistics-publication/?region=skAccessed.
August 01–2014
|
2
|
Gedye C, Hogg D, Butler M and Joshua AM:
New treatments for metastatic melanoma. CMAJ. 186:754–760. 2014.
View Article : Google Scholar : PubMed/NCBI
|
3
|
Hodi FS, ODay SJ, McDermott DF, et al:
Improved survival with ipilimumab in patients with metastatic
melanoma. N Engl J Med. 363:711–723. 2010. View Article : Google Scholar : PubMed/NCBI
|
4
|
Robert C, Thomas L, Bondarenko I, et al:
Ipilimumab plus dacarbazine for previously untreated metastatic
melanoma. N Engl J Med. 364:2517–2526. 2011. View Article : Google Scholar : PubMed/NCBI
|
5
|
Schadendorf D, Robert C, Weber JS, et al:
Pooled analysis of long-term survival data from phase II and phase
III trials of ipilimumab in metastatic or locally advanced,
unresectable melanoma. J Clin Oncol. 33:1889–1894. 2015. View Article : Google Scholar : PubMed/NCBI
|
6
|
Tarhini A: Immune-mediated adverse events
associated with ipilimumab ctla-4 blockade therapy: The underlying
mechanisms and clinical management. Scientifica (Cairo).
2013:8575192013.PubMed/NCBI
|
7
|
Topalian SL, Sznol M, McDermott DF, et al:
Survival, durable tumor remission, and long-term safety in patients
with advanced melanoma receiving nivolumab. J Clin Oncol.
32:1020–1030. 2014. View Article : Google Scholar : PubMed/NCBI
|
8
|
Robert C, Ribas A, Wolchok JD, et al:
Anti-programmed-death-receptor-1 treatment with pembrolizumab in
ipilimumab-refractory advanced melanoma: A randomised
dose-comparison cohort of a phase 1 trial. Lancet. 384:1109–1117.
2014. View Article : Google Scholar : PubMed/NCBI
|
9
|
Eggermont AM, Chiarion-Sileni V, Grob JJ,
et al: Ipilimumab versus placebo after complete resection of stage
III melanoma: Initial efficacy and safety results from the EORTC
18071 phase III trial. ASCO Meeting Abstracts. 32:LBA90082014.
|
10
|
Johnson DB, Lovly CM, Flavin M, et al:
NRAS mutation: A potential biomarker of clinical response to
immune-based therapies in metastatic melanoma (MM). ASCO Meeting
Abstracts. 31:90192013.
|
11
|
Zimmerman ZF, Storer B, Godara A, et al:
Outcomes and clinical markers associated with benefit from
ipilimumab (Ipi) in patients with advanced melanoma: A
retrospective single-institution study. ASCO Meeting Abstracts.
31:e200482013.
|
12
|
Kelderman S, Heemskerk B, van Tinteren H,
et al: Lactate dehydrogenase as a selection criterion for
ipilimumab treatment in metastatic melanoma. Cancer Immunol
Immunother. 63:449–458. 2014.PubMed/NCBI
|