Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2016 Nov 15;122(21):3354-3362.
doi: 10.1002/cncr.30259. Epub 2016 Aug 17.

The efficacy of anti-PD-1 agents in acral and mucosal melanoma

Alexander N Shoushtari  1   2 , Rodrigo R Munhoz  3 , Deborah Kuk  4 , Patrick A Ott  5 , Douglas B Johnson  6 , Katy K Tsai  7 , Suthee Rapisuwon  8 , Zeynep Eroglu  9 , Ryan J Sullivan  10 , Jason J Luke  11 , Tara C Gangadhar  12 , April K S Salama  13 , Varina Clark  3 , Clare Burias  3 , Igor Puzanov  6 , Michael B Atkins  8 , Alain P Algazi  7 , Antoni Ribas  14 , Jedd D Wolchok  3   15 , Michael A Postow  3   15
Affiliations
Comparative Study

The efficacy of anti-PD-1 agents in acral and mucosal melanoma

Alexander N Shoushtari et al. Cancer. .

Abstract

Background: Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described.

Methods: A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method.

Results: Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10 mg/kg, and 20 (33%) received nivolumab at a doses ranging from 0.3 to 10 mg/kg every 2 to 3 weeks. The objective response rate was 32% (95% confidence interval, 15%-54%) in patients with acral melanoma and 23% (95% confidence interval, 10%-40%) in those with mucosal melanoma. After a median follow-up of 20 months in the acral melanoma group and 10.6 months in the mucosal melanoma group, the median progression-free survival was 4.1 months and 3.9 months, respectively. Only 2 patients (3%) discontinued treatment because of toxicity.

Conclusions: Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to the published rates in patients with cutaneous melanoma and support the routine use of PD-1 blockade in clinical practice. Further investigation is needed to identify the mechanisms of response and resistance to therapy in these subtypes. Cancer 2016;122:3354-3362. © 2016 American Cancer Society.

Keywords: acral melanoma; anti-programmed cell death receptor 1 (anti-PD-1); immunotherapy; mucosal melanoma; nivolumab; pembrolizumab.

PubMed Disclaimer

Conflict of interest statement

ANS received travel support from BMS and is on a scientific advisory board for Vaccinex. RRM received travel grants from Merck Serrano. ZE reports no relevant disclosures. AKS has served as a consultant for BMS. MAP has received honoraria from Merck and BMS, a research grant from BMS, and has served on scientific advisory boards for Caladrius, BMS, and Amgen. DBJ is on advisory boards for BMS and Genoptix. JW has grant support from BMS and personal fees from BMS and Merck. AR has received personal fees from Merck, Novartis, Genentech, GlaxoSmithKline, Flexus, Compugen, and Amgen. He has ownership/stock in Kita Pharma.

Figures

Figure 1
Figure 1
Waterfall plot of objective response for n=60 patients with primary acral (blue) and mucosal (green) melanoma by RECIST 1.1. Diamonds indicate patients who clinically progressed without a repeat radiographic assessment (n=6). Triangles indicate best response was progressive disease due to growth in non-target lesions. Stars indicate partial responses (n=14) and CR indicates a complete response (n=2). Dashed outlines indicate investigator-assessed responses (n=26). Percent changes greater than 100% are truncated.
Figure 2
Figure 2
Median progression-free survival from time of anti-PD1 therapy. (A) Median PFS in patients with acral melanoma is 4.1 months with a median follow up of 20 months. (B) Median PFS in patients with mucosal melanoma is 3.9 months with a median follow up of 10.6 months.
Figure 3
Figure 3
Median overall survival from time of anti-PD1 therapy in patients with acral melanoma is 31.7 months with a median follow up of 20 months. Follow-up was not mature enough to report median OS in patients with mucosal melanoma.
See this image and copyright information in PMC

Comment in

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. - PubMed
    1. McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW. Incidence of noncutaneous melanomas in the U.S. Cancer. 2005;103:1000–1007. - PubMed
    1. Dupin E, Le Douarin NM. Development of melanocyte precursors from the vertebrate neural crest. Oncogene. 2003;22:3016–3023. - PubMed
    1. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–1678. - PubMed
    1. Bastian BC. The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol. 2014;9:239–271. - PMC - PubMed

MeSH terms