Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis

Abstract

Acral melanomas are a unique subset of melanomas occurring on the palms, soles, and nails. There is poor prognosis with surgery alone and no specific guidelines for the treatment of metastatic acral melanoma. This meta-analysis explored the systemic therapy outcomes for metastatic acral melanoma. Medline, Pubmed, EMBASE, and the grey literature were searched from 2010 to August 2020 for studies specifying the treatment outcome of metastatic acral melanoma. Studies were assessed by two investigators. A random-effects meta-analysis was performed and pooled Kaplan-Meier curves for progression-free survival and overall survival were created. Critical appraisal was performed using the Newcastle-Ottawa Scale. Nineteen nonrandomized studies were included, comprising 646 patients with acral melanomas and 1609 patients with nonacral melanomas treated with systemic therapy including chemotherapy, KIT-targeted drugs, as well as anti-CTLA-4 and anti-PD-1 checkpoint inhibitor therapy. Thirteen studies included Kaplan-Meier curves for progression-free survival or overall survival and 11 studies reported treatment responses. Patients with acral melanomas had worse prognosis than nonacral cutaneous melanoma (acral overall survival: median 15 months, 95% CI, 13.7-16.3 months; nonacral cutaneous: median 24 months, 95% CI, 22.6-25.4 months, P < 0.001). Acral melanoma patients treated with anti-PD-1 monotherapy had higher overall survival at 12 months (53%) compared with anti-CTLA-4 monotherapy (34%; P < 0.001). This study provides estimates of treatment response for metastatic acral melanoma, demonstrating low activity across a breadth of approved drug therapies, including anti-PD-1, the most active therapy in melanoma to date. Further research into treatments for metastatic acral melanoma is needed. Melanoma Res 31: 482-486

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022

“…A meta-analysis of studies on the treatment of metastatic acral melanoma with checkpoint inhibitors showed an objective response rate of 20%, which is significantly higher than with chemotherapy. In acral melanoma, treatment with anti-PD-1 (n Z 330) was associated with significantly better OS at 12 months (53%) than patients treated with anti-CTLA-4 therapies (n Z 94) (34% survival at 12 months, P < 0.001) [192]. The combination therapy of anti-CTLA-4 and anti-PD-1 immunotherapy showed increased efficacy with an objective response rate of 43% as compared to singleagent therapy [193].…”

Real‐world safety and effectiveness of pembrolizumab in Japanese patients with radically unresectable melanoma: An all‐case postmarketing surveillance in Japan

“… 17 , 18 , 43 This difference in the response rate could be attributed to nivolumab and ipilimumab (both immune checkpoint inhibitors) that were administered as prior therapies in some patients, suggesting the possibility of including nonresponders who were switched in this survey and the substantially lower incidence of acral melanoma and mucosal melanoma in both small‐ and large‐scale international clinical studies. 13 , 44 However, DCR (51.9%) in the RECIST assessment set of this survey was comparable with that in the pembrolizumab phase 3 KEYNOTE‐006 trial (DCR [CR + PR + SD]: 47.6% [q2w] and 46.9% [q3w]). 17 , 18 , 43 The lower ORR observed in this survey (compared with KEYNOTE‐006 studies) could also be attributed to a patient performance status (ECOG PS) of 2/3, as these patients were nonresponders in the real‐world setting in Japan.…”

“…The response rate was lower compared with that in the KEYNOTE‐006 development program (pembrolizumab administered once every 2 weeks [q2w] [36.9%] and q3w [36.1%] vs ipilimumab [11.9%]) 17,18,43 . This difference in the response rate could be attributed to nivolumab and ipilimumab (both immune checkpoint inhibitors) that were administered as prior therapies in some patients, suggesting the possibility of including nonresponders who were switched in this survey and the substantially lower incidence of acral melanoma and mucosal melanoma in both small‐ and large‐scale international clinical studies 13,44 . However, DCR (51.9%) in the RECIST assessment set of this survey was comparable with that in the pembrolizumab phase 3 KEYNOTE‐006 trial (DCR [CR + PR + SD]: 47.6% [q2w] and 46.9% [q3w]) 17,18,43 .…”

“…[8][9][10][11][12] Furthermore, the incidence of B-Raf proto-oncogene (BRAF) mutation is low in both acral and mucosal melanoma, especially compared with melanomas on the skin without CSD. 9,11,13 Compared with other cutaneous melanomas, this lower mutation burden in ALM and mucosal melanomas 11,14 could potentially explain their poor response to anti-programmed cell death protein 1 (anti-PD-1) therapy. 15 With the introduction of immune checkpoint inhibitors and other targeted therapies, systemic therapies for advanced melanoma have drastically improved.…”

“… 8 , 9 , 10 , 11 , 12 Furthermore, the incidence of B‐Raf proto‐oncogene ( BRAF ) mutation is low in both acral and mucosal melanoma, especially compared with melanomas on the skin without CSD. 9 , 11 , 13 Compared with other cutaneous melanomas, this lower mutation burden in ALM and mucosal melanomas 11 , 14 could potentially explain their poor response to anti‐programmed cell death protein 1 (anti‐PD‐1) therapy. 15 …”