Adjuvant Anti-PD-1 Antibody Therapy for Advanced Melanoma: A Multicentre Study of 78 Japanese Cases
DOI:
https://doi.org/10.2340/actadv.v102.678Keywords:
adjuvant therapy, acral melanoma, anti-PD1 Abs, RFSAbstract
Anti-PD-1 antibodies (Abs) are among the optimal adjuvant therapies for melanoma at high risk of recurrence, especially BRAF wild-type melanoma, but the anti-tumour effects of anti-PD-1 Abs in the adjuvant setting for acral melanoma have not been evaluated previously. The aim of this study was to analyse the efficacy and safety profiles of anti-PD-1 Ab monotherapy in the adjuvant setting in an Asian population including a high ratio of acral melanoma. The efficacy and safety profiles of anti-PD-1 Ab monotherapy in the adjuvant setting were retrospectively analysed in 78 Japanese patients with advanced melanoma, including 31 cases (40%) of acral melanoma. Overall relapse-free survival was 60.3% (47 of 78 cases, 95% confidence interval (CI) 49.2–70.4%), and 39.7% of patients (31 of 78 patients, 95% CI 29.6–50.8%) relapsed during the adjuvant PD-1 Ab treatment. Six cases (7.9%) discontinued the protocol due to serious adverse events. One case (1.3%) discontinued the protocol due to trauma. The relapse-free survival of acral melanoma was 25.8%, whereas that of high cumulative sun damage was 60.0%, and that of low cumulative sun damage was 57.1%. The acral type had a significantly lower 12-month relapse-free survival than other cutaneous types (p = 0.029). The acral type appeared to be an independent prognostic factor on multivariate analysis (p = 0.015). Adverse events due to anti-PD-1 antibody were observed in 37.1% overall. The results of this study suggest that anti-PD-1 Ab therapy in the adjuvant setting is less effective for acral melanoma than for other cutaneous types.
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References
Cohen JV, Buchbinder EI. The evolution of adjuvant therapy for melanoma. Curr Oncol Rep 2019; 21: 106.
https://doi.org/10.1007/s11912-019-0858-3 DOI: https://doi.org/10.1007/s11912-019-0858-3
Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017; 67: 472-492.
https://doi.org/10.3322/caac.21409 DOI: https://doi.org/10.3322/caac.21409
Fujimura T, Kambayashi Y, Ohuchi K, Muto Y, Aiba S. Treatment of advanced melanoma: past, present and future. Life (Basel) 2020; 10: 208.
https://doi.org/10.3390/life10090208 DOI: https://doi.org/10.3390/life10090208
Ascierto PA, Del Vecchio M, Mandalá M, Gogas H, Arance AM, Dalle S, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2020; 21: 1465-1477.
https://doi.org/10.1016/S1470-2045(20)30494-0 DOI: https://doi.org/10.1016/S1470-2045(20)30494-0
Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018; 378: 1789-1801.
https://doi.org/10.1056/NEJMoa1802357 DOI: https://doi.org/10.1056/NEJMoa1802357
Goydos JS, Shoen SL. Acral lentiginous melanoma. Cancer Treat Res 2016; 167: 321-329.
https://doi.org/10.1007/978-3-319-22539-5_14 DOI: https://doi.org/10.1007/978-3-319-22539-5_14
Namikawa K, Yamazaki N. Targeted therapy and immunotherapy for melanoma in Japan. Curr Treat Options Oncol 2019; 20: 7.
https://doi.org/10.1007/s11864-019-0607-8 DOI: https://doi.org/10.1007/s11864-019-0607-8
Wang Y, Zhao Y, Ma S. Racial differences in six major subtypes of melanoma: descriptive epidemiology. BMC Cancer 2016; 16: 691.
https://doi.org/10.1186/s12885-016-2747-6 DOI: https://doi.org/10.1186/s12885-016-2747-6
Li J, Wang J, Li D, Wen X, Ding Y, Liu X, et al. Adjuvant PD-1 inhibitor versus high-dose interferon α-2b for Chinese patients with cutaneous and acral melanoma: a retrospective cohort analysis. Dermatol Ther 2021; 34: e15067.
https://doi.org/10.1111/dth.15067 DOI: https://doi.org/10.1111/dth.15067
Amagai R, Muto Y, Kato H, Matsushita S, Maekawa T, Fukushima S, et al. Retrospective analysis of adjuvant therapy using dabrafenib plus trametinib in Japanese patients with advanced melanoma: analysis of 36 cases. Melanoma Res 2021; 31: 575-578.
https://doi.org/10.1097/CMR.0000000000000770 DOI: https://doi.org/10.1097/CMR.0000000000000770
Darmawan CC, Jo G, Montenegro SE, Kwak Y, Cheol L, Cho KH, et al. Early detection of acral melanoma: a review of clinical, dermoscopic, histopathologic, and molecular characteristics. J Am Acad Dermatol 2019; 81: 805-812.
https://doi.org/10.1016/j.jaad.2019.01.081 DOI: https://doi.org/10.1016/j.jaad.2019.01.081
Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol 2018; 31: 24-38.
https://doi.org/10.1038/modpathol.2017.104 DOI: https://doi.org/10.1038/modpathol.2017.104
Hayward NK, Wilmott JS, Waddell N, Johansson PA, Field MA, Nones K, et al. Whole-genome landscapes of major melanoma subtypes. Nature 2017; 545: 175-180.
https://doi.org/10.1038/nature22071 DOI: https://doi.org/10.1038/nature22071
Madore J, Strbenac D, Vilain R, Menzies AM, Yang JY, Thompson JF, et al. PD-l1 negative status is associated with lower mutation burden, differential expression of immune-related genes, and worse survival in stage III melanoma. Clin Cancer Res 2016; 22: 3915-3923.
https://doi.org/10.1158/1078-0432.CCR-15-1714 DOI: https://doi.org/10.1158/1078-0432.CCR-15-1714
Nakamura Y, Namikawa K, Yoshino K, Yoshikawa S, Uchi H, Goto K, et al. Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients. Ann Oncol 2020; 31: 1198-1206.
https://doi.org/10.1016/j.annonc.2020.05.031 DOI: https://doi.org/10.1016/j.annonc.2020.05.031
Mao L, Qi Z, Zhang L, Guo J, Si L. Immunotherapy in acral and mucosal melanoma: current status and future directions. Front Immunol 2021; 12: 680407.
https://doi.org/10.3389/fimmu.2021.680407 DOI: https://doi.org/10.3389/fimmu.2021.680407
Castaneda CA, Torres-Cabala C, Castillo M, Villegas V, Casavilca S, Cano L, et al. Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America. Clin Transl Oncol 2017; 19: 1478-1488.
https://doi.org/10.1007/s12094-017-1685-3 DOI: https://doi.org/10.1007/s12094-017-1685-3
Edwards J, Wilmott JS, Madore J, Gide TN, Quek C, Tasker A, et al. CD103+ tumor-resident CD8+ T cells are associated with improved survival in immunotherapy-naïve melanoma patients and expand significantly during anti-PD-1 treatment. Clin Cancer Res 2018; 24: 3036-3045.
https://doi.org/10.1158/1078-0432.CCR-17-2257 DOI: https://doi.org/10.1158/1078-0432.CCR-17-2257
Kambayashi Y, Fujimura T, Hidaka T, Aiba S. Biomarkers for predicting efficacies of anti-PD1 antibodies. Front Med (Lausanne) 2019; 6: 174.
https://doi.org/10.3389/fmed.2019.00174 DOI: https://doi.org/10.3389/fmed.2019.00174
Iga N, Otsuka A, Hirata M, Kataoka TR, Irie H, Nakashima C, et al. Variable indoleamine 2,3-dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy. Cancer Sci 2019; 110: 3434-3441.
https://doi.org/10.1111/cas.14195 DOI: https://doi.org/10.1111/cas.14195
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373: 23-34.
https://doi.org/10.1056/NEJMoa1504030 DOI: https://doi.org/10.1056/NEJMoa1504030
Nakamura Y, Ishitsuka Y, Tanaka R, Okiyama N, Watanabe R, Saito A, et al. Acral lentiginous melanoma and mucosal melanoma expressed less programmed-death 1 ligand than cutaneous melanoma: a retrospective study of 73 Japanese melanoma patients. J Eur Acad Dermatol Venereol 2019; 33: e424-e426.
https://doi.org/10.1111/jdv.15742 DOI: https://doi.org/10.1111/jdv.15742
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