Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma.


Journal

American journal of clinical dermatology
ISSN: 1179-1888
Titre abrégé: Am J Clin Dermatol
Pays: New Zealand
ID NLM: 100895290

Informations de publication

Date de publication:
26 Feb 2024
Historique:
accepted: 07 02 2024
medline: 27 2 2024
pubmed: 27 2 2024
entrez: 27 2 2024
Statut: aheadofprint

Résumé

With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III-IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease. With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35-50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority. Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.

Identifiants

pubmed: 38409643
doi: 10.1007/s40257-024-00852-5
pii: 10.1007/s40257-024-00852-5
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NCI NIH HHS
ID : UM1CA186690
Pays : United States
Organisme : NCI NIH HHS
ID : P50CA254865
Pays : United States
Organisme : NCI NIH HHS
ID : P30CA047904
Pays : United States

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Références

Grossmann KF, Othus M, Patel SP, et al. Adjuvant pembrolizumab versus IFNα2b or ipilimumab in resected high-risk melanoma. Cancer Discov. 2022;12(3):644–53. https://doi.org/10.1158/2159-8290.CD-21-1141 .
doi: 10.1158/2159-8290.CD-21-1141 pubmed: 34764195 pmcid: 8904282
Larkin J, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III/IV melanoma: 5-year efficacy and biomarker results from CheckMate 238. Clin Cancer Res. 2023. https://doi.org/10.1158/1078-0432.CCR-22-3145 .
doi: 10.1158/1078-0432.CCR-22-3145 pubmed: 37058595 pmcid: 10472092
Eggermont AMM, Kicinski M, Blank CU, et al. Five-year analysis of adjuvant pembrolizumab or placebo in stage III melanoma. NEJM Evid. 2022. https://doi.org/10.1056/EVIDoa2200214 .
doi: 10.1056/EVIDoa2200214 pubmed: 38319852
Dummer R, Hauschild A, Santinami M, et al. Five-year analysis of adjuvant dabrafenib plus trametinib in stage III melanoma. N Engl J Med. 2020;383(12):1139–48. https://doi.org/10.1056/NEJMoa2005493 .
doi: 10.1056/NEJMoa2005493 pubmed: 32877599
Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718–29. https://doi.org/10.1016/S0140-6736(22)00562-1 .
doi: 10.1016/S0140-6736(22)00562-1 pubmed: 35367007
Kirkwood JM, Del Vecchio M, Weber J, et al. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med. 2023. https://doi.org/10.1038/s41591-023-02583-2 .
doi: 10.1038/s41591-023-02583-2 pubmed: 37845511 pmcid: 10667090
Patel SP, Othus M, Chen Y, et al. Neoadjuvant–adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med. 2023;388(9):813–23. https://doi.org/10.1056/NEJMoa2211437 .
doi: 10.1056/NEJMoa2211437 pubmed: 36856617 pmcid: 10410527
Zhang X, Ferris L, Faries MB, Luke JJ. Debating sentinel Lymph Node Biopsy for Melanoma in the Modern Adjuvant Era. J Clin Oncol. 2023;41(26):4204–7. https://doi.org/10.1200/JCO.23.00255 .
Augustin RC, Luke JJ. Progression/recurrence-free survival 2 in adjuvant melanoma. N Engl J Med Evid. 2022. https://doi.org/10.1056/EVIDe2200240 .
doi: 10.1056/EVIDe2200240
Augustin RC, Luke JJ. PD-1 Monotherapy reigns supreme in adjuvant melanoma…but for how long? Clin Cancer Res Off J Am Assoc Cancer Res. 2023;29(17):3253–5. https://doi.org/10.1158/1078-0432.CCR-23-1194 .
doi: 10.1158/1078-0432.CCR-23-1194
Huang AC, Zappasodi R. A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance. Nat Immunol. 2022;23(5):660–70. https://doi.org/10.1038/s41590-022-01141-1 .
doi: 10.1038/s41590-022-01141-1 pubmed: 35241833 pmcid: 9106900
Eggermont AMM, Chiarion-Sileni V, Grob JJ, et al. Ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results the EORTC 18071 double-blind phase 3 randomized trial. J Clin Oncol. 2019;37(15_suppl):2512. https://doi.org/10.1200/JCO.2019.37.15_suppl.2512 .
doi: 10.1200/JCO.2019.37.15_suppl.2512
Luke JJ, Ascierto PA, Khattak MA, et al. Pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: final analysis of distant metastasis-free survival in the phase 3 KEYNOTE-716 study. J Clin Oncol. 2023;41(17):LBA9505. https://doi.org/10.1200/JCO.2023.41.17_suppl.LBA9505 .
doi: 10.1200/JCO.2023.41.17_suppl.LBA9505
Livingstone E, Zimmer L, Hassel JC, et al. Adjuvant nivolumab plus ipilimumab or nivolumab alone versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): final results of a randomised, double-blind, phase 2 trial. Lancet Lond Engl. 2022;400(10358):1117–29. https://doi.org/10.1016/S0140-6736(22)01654-3 .
doi: 10.1016/S0140-6736(22)01654-3
Khushalani NI, Vassallo M, Goldberg JD, et al. Phase II clinical and immune correlate study of adjuvant nivolumab plus ipilimumab for high-risk resected melanoma. J Immunother Cancer. 2022;10(11): e005684. https://doi.org/10.1136/jitc-2022-005684 .
doi: 10.1136/jitc-2022-005684 pubmed: 36450385 pmcid: 9717375
Weber JS, Schadendorf D, Del Vecchio M, et al. Adjuvant therapy of nivolumab combined with ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or stage IV melanoma (CheckMate 915). J Clin Oncol. 2023;41(3):517–27. https://doi.org/10.1200/JCO.22.00533 .
doi: 10.1200/JCO.22.00533 pubmed: 36162037
Augustin RC, Luke JJ. Induction exposure dose of ipilimumab and failure of adjuvant nivolumab plus ipilimumab in melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2023;41(3):443–6. https://doi.org/10.1200/JCO.22.01770 .
doi: 10.1200/JCO.22.01770
Gershenwald JE, Scolyer RA. Melanoma staging: American Joint Committee on Cancer (AJCC) 8th edition and beyond. Ann Surg Oncol. 2018;25(8):2105–10. https://doi.org/10.1245/s10434-018-6513-7 .
doi: 10.1245/s10434-018-6513-7 pubmed: 29850954
Gershenwald JE, Scolyer RA, Hess KR, 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(6):472–92. https://doi.org/10.3322/caac.21409 .
doi: 10.3322/caac.21409 pubmed: 29028110 pmcid: 5978683
Garbe C, Keim U, Amaral T, et al. Prognosis of patients with primary melanoma stage I and II according to American Joint Committee on Cancer version 8 validated in two independent cohorts: implications for adjuvant treatment. J Clin Oncol Off J Am Soc Clin Oncol. 2022;40(32):3741–9. https://doi.org/10.1200/JCO.22.00202 .
doi: 10.1200/JCO.22.00202
Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. J Clin Oncol. 2021;39(15_suppl):9506. https://doi.org/10.1200/JCO.2021.39.15_suppl.9506 .
doi: 10.1200/JCO.2021.39.15_suppl.9506
Swetter SM, Thompson JA, Albertini MR, et al. NCCN Guidelines® insights: melanoma: cutaneous, version 2.2021: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2021;19(4):364–76. https://doi.org/10.6004/jnccn.2021.0018 .
doi: 10.6004/jnccn.2021.0018 pubmed: 33845460
Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599–609. https://doi.org/10.1056/NEJMoa1310460 .
doi: 10.1056/NEJMoa1310460 pubmed: 24521106 pmcid: 4058881
Bello DM, Faries MB. The landmark series: MSLT-1, MSLT-2 and DeCOG (management of lymph nodes). Ann Surg Oncol. 2020;27(1):15–21. https://doi.org/10.1245/s10434-019-07830-w .
doi: 10.1245/s10434-019-07830-w pubmed: 31535299
Long GV, Kirkwood JMM, Hoeller C, et al. Association of biomarkers (BMs) with efficacy of adjuvant nivolumab (NIVO) vs placebo (PBO) in patients with resected stage IIB/C melanoma (CA209-76K). J Clin Oncol. 2023;41(16_suppl):9504. https://doi.org/10.1200/JCO.2023.41.16_suppl.9504 .
doi: 10.1200/JCO.2023.41.16_suppl.9504
Wilke LG, McCall LM, Posther KE, et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol. 2006;13(4):491–500. https://doi.org/10.1245/ASO.2006.05.013 .
doi: 10.1245/ASO.2006.05.013 pubmed: 16514477
Reijers ILM, Menzies AM, van Akkooi ACJ, et al. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial. Nat Med. 2022;28(6):1178–88. https://doi.org/10.1038/s41591-022-01851-x .
doi: 10.1038/s41591-022-01851-x pubmed: 35661157
Cristescu R, Mogg R, Ayers M, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018;362(6411):eaar3593. https://doi.org/10.1126/science.aar3593 .
doi: 10.1126/science.aar3593 pubmed: 30309915 pmcid: 6718162
Cui C, Xu C, Yang W, et al. Ratio of the interferon-γ signature to the immunosuppression signature predicts anti-PD-1 therapy response in melanoma. NPJ Genom Med. 2021;6(1):1–12. https://doi.org/10.1038/s41525-021-00169-w .
doi: 10.1038/s41525-021-00169-w
Jorgovanovic D, Song M, Wang L, Zhang Y. Roles of IFN-γ in tumor progression and regression: a review. Biomark Res. 2020;8(1):49. https://doi.org/10.1186/s40364-020-00228-x .
doi: 10.1186/s40364-020-00228-x pubmed: 33005420 pmcid: 7526126
Gocher AM, Workman CJ, Vignali DAA. Interferon-γ: teammate or opponent in the tumour microenvironment? Nat Rev Immunol. 2022;22(3):158–72. https://doi.org/10.1038/s41577-021-00566-3 .
doi: 10.1038/s41577-021-00566-3 pubmed: 34155388
Damotte D, Warren S, Arrondeau J, et al. The tumor inflammation signature (TIS) is associated with anti-PD-1 treatment benefit in the CERTIM pan-cancer cohort. J Transl Med. 2019;17(1):357. https://doi.org/10.1186/s12967-019-2100-3 .
doi: 10.1186/s12967-019-2100-3 pubmed: 31684954 pmcid: 6829827
Ayers M, Lunceford J, Nebozhyn M, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Investig. 2017;127(8):2930–40. https://doi.org/10.1172/JCI91190 .
doi: 10.1172/JCI91190 pubmed: 28650338 pmcid: 5531419
Spranger S, Luke JJ, Bao R, et al. Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma. Proc Natl Acad Sci USA. 2016;113(48):E7759–68. https://doi.org/10.1073/pnas.1609376113 .
doi: 10.1073/pnas.1609376113 pubmed: 27837020 pmcid: 5137753
Bao R, Stapor D, Luke JJ. Molecular correlates and therapeutic targets in T cell-inflamed versus non-T cell-inflamed tumors across cancer types. Genome Med. 2020;12(1):90. https://doi.org/10.1186/s13073-020-00787-6 .
doi: 10.1186/s13073-020-00787-6 pubmed: 33106165 pmcid: 7590690
Augustin RC, Cai WL, Luke JJ, Bao R. Facts and hopes in using omics to advance combined immunotherapy strategies. Clin Cancer Res Off J Am Assoc Cancer Res. 2024. https://doi.org/10.1158/1078-0432.CCR-22-2241 .
doi: 10.1158/1078-0432.CCR-22-2241
Augustin RC, Newman S, Li A, et al. Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma. BioRxiv Prepr Serv Biol. 2023. https://doi.org/10.1101/2023.08.24.554717 .
doi: 10.1101/2023.08.24.554717
Sanmamed MF, Perez-Gracia JL, Schalper KA, et al. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients. Ann Oncol. 2017;28(8):1988–95. https://doi.org/10.1093/annonc/mdx190 .
doi: 10.1093/annonc/mdx190 pubmed: 28595336 pmcid: 5834104
Teijeira A, Garasa S, Ochoa MC, et al. IL8, Neutrophils, and NETs in a collusion against cancer immunity and immunotherapy. Clin Cancer Res. 2021;27(9):2383–93. https://doi.org/10.1158/1078-0432.CCR-20-1319 .
doi: 10.1158/1078-0432.CCR-20-1319 pubmed: 33376096
Yuen KC, Liu LF, Gupta V, et al. High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade. Nat Med. 2020;26(5):693–8. https://doi.org/10.1038/s41591-020-0860-1 .
doi: 10.1038/s41591-020-0860-1 pubmed: 32405063 pmcid: 8286544
Davar D, Simonelli M, Gutierrez M, et al. 394 Interleukin-8–neutralizing monoclonal antibody BMS-986253 plus nivolumab (NIVO) in biomarker-enriched, primarily anti–PD-(L)1–experienced patients with advanced cancer: initial phase 1 results. J Immunother Cancer. 2020. https://doi.org/10.1136/jitc-2020-SITC2020.0394 .
doi: 10.1136/jitc-2020-SITC2020.0394
Karapetyan L, Olson AC, Gooding WE, Bao R, Chmura SJ, Luke JJ. Phase I study investigating the safety of stereotactic body radiotherapy (SBRT) with anti-PD-1 and anti-IL-8 for the treatment of multiple metastases in advanced solid tumors. J Clin Oncol. 2021;39(15_suppl):TPS2681. https://doi.org/10.1200/JCO.2021.39.15_suppl.TPS2681 .
doi: 10.1200/JCO.2021.39.15_suppl.TPS2681
Mulder EEP, Dwarkasing JT, Tempel D, et al. Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. Br J Dermatol. 2021;184(5):944–51. https://doi.org/10.1111/bjd.19499 .
doi: 10.1111/bjd.19499 pubmed: 32844403
Bailey CN, Martin BJ, Petkov VI, et al. 31-Gene expression profile testing in cutaneous melanoma and survival outcomes in a population-based analysis: a SEER collaboration. JCO Precis Oncol. 2023;7: e2300044. https://doi.org/10.1200/PO.23.00044 .
doi: 10.1200/PO.23.00044 pubmed: 37384864 pmcid: 10530886
Moding EJ, Nabet BY, Alizadeh AA, Diehn M. Detecting liquid remnants of solid tumors: circulating tumor DNA minimal residual disease. Cancer Discov. 2021;11(12):2968–86. https://doi.org/10.1158/2159-8290.CD-21-0634 .
doi: 10.1158/2159-8290.CD-21-0634 pubmed: 34785539 pmcid: 8976700
Malla M, Loree JM, Kasi PM, Parikh AR. Using circulating tumor DNA in colorectal cancer: current and evolving practices. J Clin Oncol. 2022;40(24):2846–57. https://doi.org/10.1200/JCO.21.02615 .
doi: 10.1200/JCO.21.02615 pubmed: 35839443 pmcid: 9390824
Dasari A, Lin Y, Kopetz S, et al. NRG-GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US). J Clin Oncol. 2022;40(4_suppl):TPS212. https://doi.org/10.1200/JCO.2022.40.4_suppl.TPS212 .
doi: 10.1200/JCO.2022.40.4_suppl.TPS212
Long GV, Desai K, Tang T, et al. 788O Association of pre-treatment ctDNA with disease recurrence and clinical and translational factors in patients with stage IIIB-D/IV melanoma treated with adjuvant immunotherapy (CheckMate 915). Ann Oncol. 2022;33:S904. https://doi.org/10.1016/j.annonc.2022.07.914 .
doi: 10.1016/j.annonc.2022.07.914
Lee RJ, Luke JJ. Potential of circulating tumor DNA to refine immunotherapy. Cancer. 2023;129(11):1646–8. https://doi.org/10.1002/cncr.34714 .
doi: 10.1002/cncr.34714 pubmed: 36869645
Eroglu Z, Krinshpun S, Kalashnikova E, et al. Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients. Cancer. 2023;129(11):1723–34. https://doi.org/10.1002/cncr.34716 .
doi: 10.1002/cncr.34716 pubmed: 36869646
Lee R, Rothwell DG, Jackson R, et al. DETECTION phase II/III trial: circulating tumor DNA–guided therapy for stage IIB/C melanoma after surgical resection. J Clin Oncol. 2022;40(16_suppl):TPS9603. https://doi.org/10.1200/JCO.2022.40.16_suppl.TPS9603 .
doi: 10.1200/JCO.2022.40.16_suppl.TPS9603
Lee R, Rothwell DG, Chow S, et al. CAcTUS: A parallel arm, biomarker driven, phase II feasibility trial to determine the role of circulating tumor DNA in guiding a switch between targeted therapy and immune therapy in patients with advanced cutaneous melanoma. J Clin Oncol. 2021;39(15_suppl):TPS9587. https://doi.org/10.1200/JCO.2021.39.15_suppl.TPS9587 .
doi: 10.1200/JCO.2021.39.15_suppl.TPS9587
Atkins MB, Lee SJ, Chmielowski B, et al. Combination dabrafenib and trametinib versus combination nivolumab and ipilimumab for patients with advanced BRAF-mutant melanoma: the DREAMseq trial-ECOG-ACRIN EA6134. J Clin Oncol Off J Am Soc Clin Oncol. 2023;41(2):186–97. https://doi.org/10.1200/JCO.22.01763 .
doi: 10.1200/JCO.22.01763
Ascierto PA, Mandalà M, Ferrucci PF, et al. Sequencing of ipilimumab plus nivolumab and encorafenib plus binimetinib for untreated BRAF-mutated metastatic melanoma (SECOMBIT): a randomized, three-arm, open-label phase II trial. J Clin Oncol Off J Am Soc Clin Oncol. 2023;41(2):212–21. https://doi.org/10.1200/JCO.21.02961 .
doi: 10.1200/JCO.21.02961
Washington University School of Medicine. A phase II randomized study of tiragolumab plus atezolizumab versus atezolizumab in the treatment of stage II melanoma patients who are ctDNA-positive following resection. clinicaltrials.gov; 2023. https://clinicaltrials.gov/study/NCT05060003 . Accessed 17 Oct 2023.
Tarhini AA, Stuckert J, Lee S, Sander C, Kirkwood JM. Prognostic significance of serum S100B protein in high-risk surgically resected melanoma patients participating in intergroup trial ECOG 1694. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(1):38–44. https://doi.org/10.1200/JCO.2008.17.1777 .
doi: 10.1200/JCO.2008.17.1777
Sandru A, Panaitescu E, Voinea S, et al. Prognostic value of melanoma inhibitory activity protein in localized cutaneous malignant melanoma. J Skin Cancer. 2014;2014: 843214. https://doi.org/10.1155/2014/843214 .
doi: 10.1155/2014/843214 pubmed: 25045539 pmcid: 4090457
Hügel R, Muendlein A, Volbeding L, et al. Serum levels of hepatocyte growth factor as a potential tumor marker in patients with malignant melanoma. Melanoma Res. 2016;26(4):354–60. https://doi.org/10.1097/CMR.0000000000000269 .
doi: 10.1097/CMR.0000000000000269 pubmed: 27206057
Brandacher G, Perathoner A, Ladurner R, et al. Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res Off J Am Assoc Cancer Res. 2006;12(4):1144–51. https://doi.org/10.1158/1078-0432.CCR-05-1966 .
doi: 10.1158/1078-0432.CCR-05-1966
Ding L, Gosh A, Lee DJ, et al. Prognostic biomarkers of cutaneous melanoma. Photodermatol Photoimmunol Photomed. 2022;38(5):418–34. https://doi.org/10.1111/phpp.12770 .
doi: 10.1111/phpp.12770 pubmed: 34981569
Li P, He QY, Luo CQ, Qian LY. Circulating miR-221 expression level and prognosis of cutaneous malignant melanoma. Med Sci Monit Int Med J Exp Clin Res. 2014;20:2472–7. https://doi.org/10.12659/MSM.891327 .
doi: 10.12659/MSM.891327
Martino MTD, Arbitrio M, Caracciolo D, et al. miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: a systematic review. Mol Ther Nucl Acids. 2022;27:1191–224. https://doi.org/10.1016/j.omtn.2022.02.005 .
doi: 10.1016/j.omtn.2022.02.005
Kanemaru H, Fukushima S, Yamashita J, et al. The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci. 2011;61(3):187–93. https://doi.org/10.1016/j.jdermsci.2010.12.010 .
doi: 10.1016/j.jdermsci.2010.12.010 pubmed: 21273047
Sigalotti L, Covre A, Fratta E, et al. Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients. J Transl Med. 2012;10:185. https://doi.org/10.1186/1479-5876-10-185 .
doi: 10.1186/1479-5876-10-185 pubmed: 22950745 pmcid: 3539917
Thomas NE, Slater NA, Edmiston SN, et al. DNA methylation profiles in primary cutaneous melanomas are associated with clinically significant pathologic features. Pigment Cell Melanoma Res. 2014;27(6):1097–105. https://doi.org/10.1111/pcmr.12289 .
doi: 10.1111/pcmr.12289 pubmed: 24986547 pmcid: 4211983
Garraway LA, Widlund HR, Rubin MA, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 2005;436(7047):117–22. https://doi.org/10.1038/nature03664 .
doi: 10.1038/nature03664 pubmed: 16001072
Ballotti R, Cheli Y, Bertolotto C. The complex relationship between MITF and the immune system: a melanoma immunotherapy (response) factor? Mol Cancer. 2020;19(1):170. https://doi.org/10.1186/s12943-020-01290-7 .
doi: 10.1186/s12943-020-01290-7 pubmed: 33276788 pmcid: 7718690
Blancafort A, Giró-Perafita A, Oliveras G, et al. Dual fatty acid synthase and HER2 signaling blockade shows marked antitumor activity against breast cancer models resistant to anti-HER2 drugs. PLoS ONE. 2015;10(6): e0131241. https://doi.org/10.1371/journal.pone.0131241 .
doi: 10.1371/journal.pone.0131241 pubmed: 26107737 pmcid: 4479882
Bagati A, Moparthy S, Bianchi-Smiraglia A, et al. Melanoma suppressor functions of the carcinoma oncogene FOXQ1. Cell Rep. 2017;20(12):2820–32. https://doi.org/10.1016/j.celrep.2017.08.057 .
doi: 10.1016/j.celrep.2017.08.057 pubmed: 28930679 pmcid: 5664207
Cykowska A, Hofmann UK, Tiwari A, Kosnopfel C, Riester R, Danalache M. Biomechanical and biochemical assessment of YB-1 expression in A375 melanoma cell line: exploratory study. Front Mol Med. 2023. https://doi.org/10.3389/fmmed.2023.1050487 .
doi: 10.3389/fmmed.2023.1050487
Wang X, Fan D, Yang Y, Gimple RC, Zhou S. Integrative multi-omics approaches to explore immune cell functions: challenges and opportunities. iScience. 2023;26(4):106359. https://doi.org/10.1016/j.isci.2023.106359 .
doi: 10.1016/j.isci.2023.106359 pubmed: 37009227 pmcid: 10060681
Ma A, Xin G, Ma Q. The use of single-cell multi-omics in immuno-oncology. Nat Commun. 2022;13(1):2728. https://doi.org/10.1038/s41467-022-30549-4 .
doi: 10.1038/s41467-022-30549-4 pubmed: 35585090 pmcid: 9117235
Sun R, Lerousseau M, Briend-Diop J, et al. Radiomics to evaluate interlesion heterogeneity and to predict lesion response and patient outcomes using a validated signature of CD8 cells in advanced melanoma patients treated with anti-PD1 immunotherapy. J Immunother Cancer. 2022;10(10): e004867. https://doi.org/10.1136/jitc-2022-004867 .
doi: 10.1136/jitc-2022-004867 pubmed: 36307149 pmcid: 9621183
Colen RR, Rolfo C, Ak M, et al. Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers. J Immunother Cancer. 2021;9(4): e001752. https://doi.org/10.1136/jitc-2020-001752 .
doi: 10.1136/jitc-2020-001752 pubmed: 33849924 pmcid: 8051405
Ghini V, Laera L, Fantechi B, et al. Metabolomics to assess response to immune checkpoint inhibitors in patients with non-small-cell lung cancer. Cancers. 2020;12(12):3574. https://doi.org/10.3390/cancers12123574 .
doi: 10.3390/cancers12123574 pubmed: 33265926 pmcid: 7760033
Szalay AS, Taube JM. Data-rich spatial profiling of cancer tissue: astronomy informs pathology. Clin Cancer Res Off J Am Assoc Cancer Res. 2022;28(16):3417–24. https://doi.org/10.1158/1078-0432.CCR-19-3748 .
doi: 10.1158/1078-0432.CCR-19-3748
Davis-Marcisak EF, Deshpande A, Stein-O’Brien GL, et al. From bench to bedside: single-cell analysis for cancer immunotherapy. Cancer Cell. 2021;39(8):1062–80. https://doi.org/10.1016/j.ccell.2021.07.004 .
doi: 10.1016/j.ccell.2021.07.004 pubmed: 34329587 pmcid: 8406623
Johannet P, Coudray N, Donnelly DM, et al. Using machine learning algorithms to predict immunotherapy response in patients with advanced melanoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2021;27(1):131–40. https://doi.org/10.1158/1078-0432.CCR-20-2415 .
doi: 10.1158/1078-0432.CCR-20-2415
Kong J, Ha D, Lee J, et al. Network-based machine learning approach to predict immunotherapy response in cancer patients. Nat Commun. 2022;13(1):3703. https://doi.org/10.1038/s41467-022-31535-6 .
doi: 10.1038/s41467-022-31535-6 pubmed: 35764641 pmcid: 9240063
Wei F, Azuma K, Nakahara Y, et al. Machine learning for prediction of immunotherapeutic outcome in non-small-cell lung cancer based on circulating cytokine signatures. J Immunother Cancer. 2023;11(7): e006788. https://doi.org/10.1136/jitc-2023-006788 .
doi: 10.1136/jitc-2023-006788 pubmed: 37433717 pmcid: 10347453
Eggermont AMM, Blank CU, Mandalà M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(5):643–54. https://doi.org/10.1016/S1470-2045(21)00065-6 .
doi: 10.1016/S1470-2045(21)00065-6 pubmed: 33857412
Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35. https://doi.org/10.1056/NEJMoa1709030 .
doi: 10.1056/NEJMoa1709030 pubmed: 28891423
Helgadottir H, Ny L, Ullenhag GJ, et al. Survival after introduction of adjuvant treatment in stage III melanoma: a nationwide registry-based study. J Natl Cancer Inst. 2023;115(9):1077–84. https://doi.org/10.1093/jnci/djad081 .
doi: 10.1093/jnci/djad081 pubmed: 37227040 pmcid: 10483326
George B, Kurzrock R. Progression-free survival 2: is it ready for prime time? Cancer. 2022;128(7):1361–2. https://doi.org/10.1002/cncr.34086 .
doi: 10.1002/cncr.34086 pubmed: 34985767
Woodford RG, Zhou DDX, Kok PS, et al. The validity of progression-free survival 2 as a surrogate trial end point for overall survival. Cancer. 2022;128(7):1449–57. https://doi.org/10.1002/cncr.34085 .
doi: 10.1002/cncr.34085 pubmed: 34985773
Livingstone A, Agarwal A, Stockler MR, Menzies AM, Howard K, Morton RL. Preferences for immunotherapy in melanoma: a systematic review. Ann Surg Oncol. 2020;27(2):571–84. https://doi.org/10.1245/s10434-019-07963-y .
doi: 10.1245/s10434-019-07963-y pubmed: 31664622
De Meza MM, Blokx WAM, Bonenkamp JJ, et al. Adjuvant BRAF-MEK inhibitors versus anti PD-1 therapy in stage III melanoma: a propensity-matched outcome analysis. Cancers. 2023;15(2):409. https://doi.org/10.3390/cancers15020409 .
doi: 10.3390/cancers15020409 pubmed: 36672358 pmcid: 9857200
Ascierto PA, Stroyakovskiy D, Gogas H, et al. Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study. Lancet Oncol. 2023;24(1):33–44. https://doi.org/10.1016/S1470-2045(22)00687-8 .
doi: 10.1016/S1470-2045(22)00687-8 pubmed: 36460017
Ribas A, Ferrucci PF, Atkinson V, et al. Pembrolizumab (pembro) plus dabrafenib (dab) and trametinib (tram) in BRAFV600E/K-mutant melanoma: long-term follow-up of KEYNOTE-022 parts 1, 2, and 3. J Clin Oncol. 2022;40(16_suppl):9516. https://doi.org/10.1200/JCO.2022.40.16_suppl.9516 .
doi: 10.1200/JCO.2022.40.16_suppl.9516
Dummer R, Long GV, Robert C, et al. Randomized phase III trial evaluating spartalizumab plus dabrafenib and trametinib for BRAF V600-mutant unresectable or metastatic melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2022;40(13):1428–38. https://doi.org/10.1200/JCO.21.01601 .
doi: 10.1200/JCO.21.01601
Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24–34. https://doi.org/10.1056/NEJMoa2109970 .
doi: 10.1056/NEJMoa2109970 pubmed: 34986285 pmcid: 9844513
Bristol-Myers S. A phase 3, randomized, double-blind study of adjuvant immunotherapy with nivolumab + relatlimab fixed-dose combination versus nivolumab monotherapy after complete resection of stage III-IV melanoma. clinicaltrials.gov; 2022. https://clinicaltrials.gov/ct2/show/NCT05002569 . Accessed 14 Sept 2022.
Hamid O, Lewis KD, Weise AM, et al. Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: post adjuvant PD-1 analysis. J Clin Oncol. 2023;41(16_suppl):9501. https://doi.org/10.1200/JCO.2023.41.16_suppl.9501 .
doi: 10.1200/JCO.2023.41.16_suppl.9501
Dummer R, Robert C, Scolyer RA, et al. Abstract CT002: KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma. Cancer Res. 2023;83(8_Supplement):CT002. https://doi.org/10.1158/1538-7445.AM2023-CT002 .
doi: 10.1158/1538-7445.AM2023-CT002
Eggermont AM, Ascierto PA, Khushalani NI, et al. PIVOT-12: a phase III study of adjuvant bempegaldesleukin plus nivolumab in resected stage III/IV melanoma at high risk for recurrence. Future Oncol Lond Engl. 2022;18(8):903–13. https://doi.org/10.2217/fon-2021-1286 .
doi: 10.2217/fon-2021-1286
Long GV, Eggermont AM, Gershenwald JE, et al. KEYVIBE-010: Adjuvant coformulated vibostolimab with pembrolizumab versus adjuvant pembrolizumab in patients with high-risk stage II–IV melanoma. J Clin Oncol. 2023;41(16_suppl):TPS9611. https://doi.org/10.1200/JCO.2023.41.16_suppl.TPS9611 .
doi: 10.1200/JCO.2023.41.16_suppl.TPS9611
Khattak A, Weber JS, Meniawy T, et al. Distant metastasis-free survival results from the randomized, phase 2 mRNA-4157-P201/KEYNOTE-942 trial. J Clin Oncol. 2023;41(17_suppl):LBA9503. https://doi.org/10.1200/JCO.2023.41.17_suppl.LBA9503 .
doi: 10.1200/JCO.2023.41.17_suppl.LBA9503
Van Akkooi ACJ, Hauschild A, Long GV, et al. Phase III study of adjuvant encorafenib plus binimetinib versus placebo in fully resected stage IIB/C BRAFV600-mutated melanoma: COLUMBUS-AD study design. J Clin Oncol. 2023;41(16_suppl):TPS9601. https://doi.org/10.1200/JCO.2023.41.16_suppl.TPS9601 .
Krishnamoorthy M, Lenehan JG, Maleki VS. Neoadjuvant immunotherapy for high-risk, resectable malignancies: scientific rationale and clinical challenges. J Natl Cancer Inst. 2021;113(7):823–32. https://doi.org/10.1093/jnci/djaa216 .
doi: 10.1093/jnci/djaa216 pubmed: 33432320 pmcid: 8246900
Patel S, Othus M, Wright P, et al. LBA48 Pathologic response and exploratory analyses of neoadjuvant-adjuvant versus adjuvant pembrolizumab (PEM) for resectable stage IIIb-IV melanoma from SWOG S1801. Ann Oncol. 2023;34:S1288. https://doi.org/10.1016/j.annonc.2023.10.042 .
doi: 10.1016/j.annonc.2023.10.042
Rozeman EA, Hoefsmit EP, Reijers ILM, et al. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma. Nat Med. 2021;27(2):256–63. https://doi.org/10.1038/s41591-020-01211-7 .
doi: 10.1038/s41591-020-01211-7 pubmed: 33558721
Blank CU, Reijers ILM, Saw RPM, et al. Survival data of PRADO: a phase 2 study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma. J Clin Oncol. 2022;40(16_suppl):9501. https://doi.org/10.1200/JCO.2022.40.16_suppl.9501 .
doi: 10.1200/JCO.2022.40.16_suppl.9501
Reijers ILM, Rao D, Versluis JM, et al. IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma. J Exp Med. 2023;220(5): e20221952. https://doi.org/10.1084/jem.20221952 .
doi: 10.1084/jem.20221952 pubmed: 36920329 pmcid: 10037109
Lucas MW, Lijnsvelt J, Pulleman S, et al. The NADINA trial: a multicenter, randomised, phase 3 trial comparing the efficacy of neoadjuvant ipilimumab plus nivolumab with standard adjuvant nivolumab in macroscopic resectable stage III melanoma. J Clin Oncol. 2022;40(16_suppl):TPS9605. https://doi.org/10.1200/JCO.2022.40.16_suppl.TPS9605 .
Amaria RN, Postow M, Burton EM, et al. Neoadjuvant relatlimab and nivolumab in resectable melanoma. Nature. 2022;611(7934):155–60. https://doi.org/10.1038/s41586-022-05368-8 .
doi: 10.1038/s41586-022-05368-8 pubmed: 36289334 pmcid: 9607737
Melanoma Institute Australia. A phase 2, open label, single arm, clinical trial of neoadjuvant relatlimab and nivolumab in high risk, clinical stage II cutaneous melanoma. clinicaltrials.gov; 2023. https://clinicaltrials.gov/study/NCT05418972 . Accessed 31 Dec 2022.
Knight DA, Ngiow SF, Li M, et al. Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Investig. 2013;123(3):1371–81. https://doi.org/10.1172/JCI66236 .
doi: 10.1172/JCI66236 pubmed: 23454771 pmcid: 3582139
Donia M, Fagone P, Nicoletti F, et al. BRAF inhibition improves tumor recognition by the immune system: potential implications for combinatorial therapies against melanoma involving adoptive T-cell transfer. Oncoimmunology. 2012;1(9):1476–83. https://doi.org/10.4161/onci.21940 .
doi: 10.4161/onci.21940 pubmed: 23264894 pmcid: 3525603
Mayo Clinic. Neoadjuvant therapy for patients with high risk stage III melanoma: a pilot clinical trial. clinicaltrials.gov; 2023. https://clinicaltrials.gov/study/NCT03554083 . Accessed 31 Dec 2022.
Ascierto PA, Cioli E, Chiarion-Sileni V, et al. Neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma: NEO-TIM, a phase II randomized non-comparative study. Front Oncol. 2023;13:1107307. https://doi.org/10.3389/fonc.2023.1107307 .
doi: 10.3389/fonc.2023.1107307 pubmed: 36845751 pmcid: 9949553
Long GV, Carlino MS, Au-Yeung G, et al. NeoTrio: randomized trial of neoadjuvant (NAT) pembrolizumab (Pembro) alone, in sequence (SEQ) with, or concurrent (CON) with dabrafenib plus trametinib (D+T) in resectable BRAF-mutant stage III melanoma to determine optimal combination of therapy. J Clin Oncol. 2022;40(16_suppl):9503–9503. https://doi.org/10.1200/JCO.2022.40.16_suppl.9503 .
doi: 10.1200/JCO.2022.40.16_suppl.9503
Tarhini A, Eroglu Z, Sarnaik A, et al. 617 Neoadjuvant intratumoral TAVO-EP (plasmid IL-12 electro gene transfer) in combination with nivolumab; preliminary clinical and biomarker data in patients with operable locoregionally advanced melanoma. J Immunother Cancer. 2022. https://doi.org/10.1136/jitc-2022-SITC2022.0617 .
Incorporated OM. OncoSec announces clinical data of the KEYNOTE-695 TRIAL ASSESSING TAVO
Philogen S.p.A. A pivotal phase iii, open-label, randomized, controlled multi-center study of the efficacy of L19IL2/L19TNF neoadjuvant intratumoral treatment followed by surgery versus surgery alone in clinical stage III B/C melanoma patients. clinicaltrials.gov; 2023. https://clinicaltrials.gov/study/NCT02938299 . Accessed 31 Dec 2022.
Idera pharmaceuticals shares positive results from investigator-sponsored trial in melanoma patients at Amsterdam UMC—enrollment stopped early for efficacy. BioSpace. Accessed 3 Nov 2023. https://www.biospace.com/article/idera-pharmaceuticals-shares-positive-results-from-investigator-sponsored-trial-in-melanoma-patients-at-amsterdam-umc-enrollment-stopped-early-for-efficacy-/ .

Auteurs

Ryan C Augustin (RC)

UPMC Hillman Cancer Center, 5150 Centre Ave. Room 1.27C, Pittsburgh, PA, 15232, USA.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.

Jason J Luke (JJ)

UPMC Hillman Cancer Center, 5150 Centre Ave. Room 1.27C, Pittsburgh, PA, 15232, USA. lukejj@upmc.edu.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. lukejj@upmc.edu.

Classifications MeSH