Highlights
- •Phase II study of ipilimumab in adolescents with advanced melanoma.
- •At 1 year, 3 of 4 patients on 3 mg/kg and 5 of 8 patients on 10 mg/kg were alive.
- •Two patients on 10 mg/kg had partial response and 1 on 3 mg/kg had stable disease.
- •The safety profile was consistent with that observed in the adult population.
- •The study was stopped due to slow accrual of patients.
Abstract
Background
Ipilimumab is approved for the treatment of advanced melanoma in adults; however,
little information on the efficacy and safety of ipilimumab in younger patients is
available.
Methods
Patients aged 12 to <18 years with previously treated or untreated, unresectable stage
III or IV malignant melanoma received ipilimumab 3 or 10 mg/kg every 3 weeks. Primary
end-points were 1-year overall survival and safety.
Results
Over a period of 3.5 years, 12 patients received ipilimumab at either 3 mg/kg (n = 4)
or 10 mg/kg (n = 8). The median number of ipilimumab doses was four for 3 mg/kg and
three for 10 mg/kg. At 1 year, three of four patients on 3 mg/kg and five of eight
patients on 10 mg/kg were alive. Two patients on 10 mg/kg had partial response, and
one on 3 mg/kg had stable disease. One patient had durable partial response at 3 years
without further treatment, at time of this report. There was one grade 3/4 immune-mediated
adverse reaction with 3 mg/kg and five with 10 mg/kg. There were no treatment-related
deaths. The study was stopped due to slow accrual.
Conclusions
At >1 year follow-up, ipilimumab demonstrated activity in melanoma patients aged 12
to <18 years, with a similar safety profile as that seen in adults. Our trial highlights
the difficulties of enrolling younger patients with rare diseases in clinical trials
for treatments that are approved in adults, suggesting adolescents with cancer types
occurring predominantly in adults should be considered for inclusion in adult trials
of promising new drugs.
Clinical trial registration: NCT01696045.
Keywords
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References
- Incidence of childhood and adolescent melanoma in the United States: 1973–2009.Pediatrics. 2013; 131: 846-854
- The genomic landscape of childhood and adolescent melanoma.J Invest Dermatol. 2015; 135: 816-823
- Improved survival with ipilimumab in patients with metastatic melanoma.N Engl J Med. 2010; 363: 711-723
- Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma.J Clin Oncol. 2015; 33: 1889-1894
- Phase I clinical trial of ipilimumab in pediatric patients with advanced solid tumors.Clin Cancer Res. 2016; 22: 1364-1370
- Therapeutic effect and tolerance of ipilimumab in metastatic malignant melanoma in children- V. Case report.Klin Onkol. 2015; 28 ([Article in Czech]): S115-S120
- Yervoy [package insert]. Bristol-Myers Squibb Inc, Princeton, NJJuly 2017
- Exposure-response relationships of the efficacy and safety of ipilimumab in patients with advanced melanoma.Clin Cancer Res. 2013; 19: 3977-3986
- Model-based clinical pharmacology profiling of ipilimumab in patients with advanced melanoma.Br J Clin Pharmacol. 2014; 78: 106-117
- Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases.Cancer Immunol Immunother. 2009; 58: 1297-1306
- Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.Lancet Oncol. 2010; 11: 155-164
- Is the European pediatric medicine regulation working for children and adolescents with cancer?.Clin Cancer Res. 2013; 19 (Epub 2013 Jan 17): 1315-1325https://doi.org/10.1158/1078-0432.CCR-12-2551
- Enrolling adolescents in disease/target-appropriate adult oncology clinical trials of investigational agents.Clin Cancer Res. 2017; 23: 9-12
- Early phase clinical trials of anticancer agents in children and adolescents – an ITCC perspective.Nat Rev Clin Oncol. 2017; 14: 497-507
Article info
Publication history
Published online: October 26, 2017
Accepted:
September 24,
2017
Received:
September 1,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Most adolescents' melanomas are conventional malignant adult-type melanomasEuropean Journal of CancerVol. 95
- PreviewPaediatric melanoma has been characterised with age ranges from <10 to ≤21 years [1]. Conventional malignant melanomas occur rarely before, mostly after the 18th birthday, but are genomically comparable [2]. In the past, patients' age was more an academic question. The growing number of effective drugs, drug combinations and means to differentiate true paediatric melanomas (Spitz nevus, Spitzoid melanoma, melanoma arising in giant congenital nevi [2]) from adult-type conventional melanomas require a change of paradigm.
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