Therapeutic goals include:
Treatment is individualized according to prognosis and the desired outcome of therapy. Indications for treatment are similar for the different epidemiologic forms of KS (classic [sporadic]; endemic [observed in sub-Saharan Africa]; HIV-associated; iatrogenic [transplant-related]).
Observation may be an option for patients without HIV who have cosmetically acceptable lesions and no other symptoms. People with HIV with limited asymptomatic cutaneous disease can receive antiretroviral therapy (ART) alone.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
For patients with iatrogenic KS, careful reduction of immunosuppressive therapy should be considered. Local and/or systemic therapy can be considered if there is rapid progression, or for patients with symptomatic and/or cosmetically deforming or stigmatizing disease.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[3]Lebbe C, Garbe C, Stratigos AJ, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019 Jun;114:117-27.
http://www.ncbi.nlm.nih.gov/pubmed/31096150?tool=bestpractice.com
[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
People with HIV who require treatment should receive the least toxic therapy possible.
KS with systemic involvement, particularly visceral and lymph node involvement, can carry a poor prognosis. These patients may require supportive care for nutritional, mobility, social, and psychological wellbeing; to control pain; and to monitor and treat disease complications if they occur.
Local therapy
Considered for individual cutaneous lesions (symptomatic and/or cosmetically disturbing) and for patients unable to tolerate systemic therapy.[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
Options include:[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[3]Lebbe C, Garbe C, Stratigos AJ, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019 Jun;114:117-27.
http://www.ncbi.nlm.nih.gov/pubmed/31096150?tool=bestpractice.com
[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
Topical therapies (e.g., retinoids such as alitretinoin, or imiquimod)
Radiation therapy
Intralesional chemotherapy (vinblastine or bleomycin)
Cryotherapy
Marginal excision
Electrodesiccation and curettage.
Marginal excision, electrodesiccation and curettage, cryotherapy, and intralesional chemotherapy are typically reserved for local control of small, symptomatic lesions. Wide local excision for negative margins is not indicated for KS.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
Cryotherapy should be performed by a clinician with expertise in cutaneous cancer cryotherapy.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
Radiation therapy is an effective local treatment; preferred for larger, deeper lesions when systemic therapy is not suitable or effective.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[3]Lebbe C, Garbe C, Stratigos AJ, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019 Jun;114:117-27.
http://www.ncbi.nlm.nih.gov/pubmed/31096150?tool=bestpractice.com
[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
Various radiation therapy dosing regimens have been used. Localized, bulky lesions, particularly those that are ulcerated or infected, may be treated with local external beam radiation therapy.[54]Caccialanza M, Marca S, Piccinno R, et al. Radiotherapy of classic and human immunodeficiency virus-related Kaposi's sarcoma: results in 1482 lesions. J Eur Acad Dermatol Venereol. 2008 Mar;22(3):297-302.
http://www.ncbi.nlm.nih.gov/pubmed/18269597?tool=bestpractice.com
Patients should be informed of the risk of secondary cancers, radiation therapy-induced toxicity, and other adverse effects. Lower-dose regimens can reduce toxicity, and are preferred for smaller, superficial lesions, and palliative therapy.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
Systemic therapy
Indications for systemic treatment include:[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
Widespread skin involvement
Extensive mucosal lesions
Symptomatic edema
Rapidly progressive disease
Symptomatic visceral disease
KS flare (exacerbation).
Liposomal doxorubicin is recommended as first-line treatment.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[3]Lebbe C, Garbe C, Stratigos AJ, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019 Jun;114:117-27.
http://www.ncbi.nlm.nih.gov/pubmed/31096150?tool=bestpractice.com
[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
Myelosuppression is the most important dose-limiting toxicity with liposomal doxorubicin, while neuropathy and alopecia occur infrequently. Cardiotoxicity is very rare, even after the administration of high cumulative doses.
Paclitaxel is an effective second-line treatment. However, there is an increased incidence of alopecia, myalgia, and arthralgia as well as the potential for aggravating preexisting neuropathy.
Nanoparticle albumin-bound (nab)-paclitaxel may be an alternative option if the patient is not able to tolerate paclitaxel.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[55]Fortino S, Santoro M, Iuliano E, et al. Treatment of Kaposi's sarcoma (KS) with nab-paclitaxel. Paper presented at: XVIII National Congress of Medical Oncology. 28-30 Oct 2016. Rome, Italy. Session S: miscellanea. Abstract S63. Ann Oncol. 2016 Sep;27(Suppl 4):iv124.
https://www.annalsofoncology.org/article/S0923-7534(19)56963-0/fulltext
ART for HIV-associated KS (formerly known as epidemic or AIDS-related KS)
Initiation of ART is strongly recommended for all HIV-infected patients, regardless of CD4+ T-cell count.[56]National Institutes of Health, Centers for Disease Control and Prevention, and HIV Medicine Association of the Infectious Diseases Society of America. US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2024 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new
[57]World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach - second edition, 2016. Jun 2016 [internet publication].
https://www.who.int/publications/i/item/9789241549684
ART should be started immediately after HIV diagnosis (on the day of diagnosis, if possible, and within 7 days) to increase uptake and engagement, and accelerate the time to viral suppression.[58]Mateo-Urdiales A, Johnson S, Smith R, et al. Rapid initiation of antiretroviral therapy for people living with HIV. Cochrane Database Syst Rev. 2019 Jun 17;6(6):CD012962.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6575156
http://www.ncbi.nlm.nih.gov/pubmed/31206168?tool=bestpractice.com
[59]World Health Organization. Guidelines for mnaging advanced HIV disease and rapid initiation of antiretroviral therapy. Geneva: World Health Organization; 2017.
https://www.ncbi.nlm.nih.gov/books/NBK475977
http://www.ncbi.nlm.nih.gov/pubmed/29341560?tool=bestpractice.com
Initiation should not be delayed in people with confirmed HIV infection while awaiting testing results, including safety testing and drug-resistance testing; the regimen can be modified when these results are reported.[56]National Institutes of Health, Centers for Disease Control and Prevention, and HIV Medicine Association of the Infectious Diseases Society of America. US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2024 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new
See HIV infection.
Optimal control of HIV infection using ART is a key component in the treatment of HIV-associated KS. A stage-stratified approach to managing patients with HIV-associated KS appears to be beneficial; one Cochrane review reported that, in patients with either severe or progressive KS, ART plus chemotherapy may reduce disease progression compared with ART alone.[60]Gbabe OF, Okwundu CI, Dedicoat M, et al. Treatment of severe or progressive Kaposi's sarcoma in HIV-infected adults. Cochrane Database Syst Rev. 2014 Sep 1;(9):CD003256.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003256.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/25313415?tool=bestpractice.com
Patients who are on ART alone should be reassessed within 4 weeks of starting treatment, including monitoring for immune reconstitution inflammatory syndrome (IRIS).[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
See Complications.
Immunosuppression for iatrogenic (transplant-related) KS
Consider adjusting immunosuppression for iatrogenic KS. In renal transplant recipients, discontinuation of immunosuppressive therapy is an option if dialysis is available.[20]Mbulaiteye SM, Engels EA. Kaposi's sarcoma risk among transplant recipients in the United States (1993-2003). Int J Cancer. 2006 Dec 1;119(11):2685-91.
https://onlinelibrary.wiley.com/doi/10.1002/ijc.22233
http://www.ncbi.nlm.nih.gov/pubmed/16929513?tool=bestpractice.com
[61]Shepherd FA, Maher E, Cardella C, et al. Treatment of Kaposi's sarcoma after solid organ transplantation. J Clin Oncol. 1997 Jun;15(6):2371-7.
http://www.ncbi.nlm.nih.gov/pubmed/9196152?tool=bestpractice.com
Modifying the dose of immunosuppressive drugs may be more difficult in patients with a heart or liver transplant.
Switching to sirolimus for immunosuppression may be sufficient for KS control and treatment; for aggressive or advanced disease, systemic therapy may be given alongside sirolimus.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[3]Lebbe C, Garbe C, Stratigos AJ, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019 Jun;114:117-27.
http://www.ncbi.nlm.nih.gov/pubmed/31096150?tool=bestpractice.com
[5]Esser S, Schöfer H, Hoffmann C, et al. S1 guidelines for the Kaposi sarcoma. J Dtsch Dermatol Ges. 2022 Jun;20(6):892-904.
https://onlinelibrary.wiley.com/doi/10.1111/ddg.14788
http://www.ncbi.nlm.nih.gov/pubmed/35657085?tool=bestpractice.com
Refractory or relapsed KS
Pomalidomide, bortezomib, gemcitabine, lenalidomide, or vinorelbine can be considered as first-line for patients with refractory/relapsed KS.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[62]Polizzotto MN, Uldrick TS, Wyvill KM, et al. Pomalidomide for symptomatic Kaposi's sarcoma in people with and without HIV infection: a phase I/II study. J Clin Oncol. 2016 Dec;34(34):4125-31.
https://ascopubs.org/doi/10.1200/JCO.2016.69.3812
http://www.ncbi.nlm.nih.gov/pubmed/27863194?tool=bestpractice.com
[63]Ramaswami R, Polizzotto MN, Lurain K, et al. Safety, activity, and long-term outcomes of pomalidomide in the treatment of Kaposi sarcoma among individuals with or without HIV infection. Clin Cancer Res. 2022 Mar 1;28(5):840-50.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898289
http://www.ncbi.nlm.nih.gov/pubmed/34862247?tool=bestpractice.com
[64]Reid EG, Suazo A, Lensing SY, et al; AIDS Malignancy Consortium (AMC). Pilot trial AMC-063: safety and efficacy of bortezomib in AIDS-associated Kaposi sarcoma. Clin Cancer Res. 2020 Feb 1;26(3):558-65.
https://aacrjournals.org/clincancerres/article/26/3/558/83202/Pilot-Trial-AMC-063-Safety-and-Efficacy-of
http://www.ncbi.nlm.nih.gov/pubmed/31624104?tool=bestpractice.com
[65]Pourcher V, Desnoyer A, Assoumou L, et al. Phase II trial of lenalidomide in HIV-infected patients with previously treated Kaposi's sarcoma: results of the ANRS 154 Lenakap Trial. AIDS Res Hum Retroviruses. 2017 Jan;33(1):1-10.
http://www.ncbi.nlm.nih.gov/pubmed/27405442?tool=bestpractice.com
[66]Reid EG, Shimabukuro K, Moore P, et al. AMC-070: Lenalidomide is safe and effective in HIV-associated Kaposi sarcoma. Clin Cancer Res. 2022 Jun 13;28(12):2646-56.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9197984
http://www.ncbi.nlm.nih.gov/pubmed/35247913?tool=bestpractice.com
[67]Strother RM, Gregory KM, Pastakia SD, et al. Retrospective analysis of the efficacy of gemcitabine for previously treated AIDS-associated Kaposi's sarcoma in western Kenya. Oncology. 2010;78(1):5-11.
https://karger.com/ocl/article/78/1/5/327633/Retrospective-Analysis-of-the-Efficacy-of
http://www.ncbi.nlm.nih.gov/pubmed/20215784?tool=bestpractice.com
[68]Nasti G, Errante D, Talamini R, et al. Vinorelbine is an effective and safe drug for AIDS-related Kaposi's sarcoma: results of a phase II study. J Clin Oncol. 2000 Apr;18(7):1550-7.
http://www.ncbi.nlm.nih.gov/pubmed/10735904?tool=bestpractice.com
Each of these treatment options can be tried in any order, and a specific drug can be repeated (if tolerated and the duration of response is 3 months or more).[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
Myelosuppression and thromboembolic complications may occur.
In the US, pomalidomide is approved under accelerated approval for patients with HIV-associated KS whose disease has progressed despite the initiation of ART, or in patients with KS who are HIV-negative.[62]Polizzotto MN, Uldrick TS, Wyvill KM, et al. Pomalidomide for symptomatic Kaposi's sarcoma in people with and without HIV infection: a phase I/II study. J Clin Oncol. 2016 Dec;34(34):4125-31.
https://ascopubs.org/doi/10.1200/JCO.2016.69.3812
http://www.ncbi.nlm.nih.gov/pubmed/27863194?tool=bestpractice.com
[63]Ramaswami R, Polizzotto MN, Lurain K, et al. Safety, activity, and long-term outcomes of pomalidomide in the treatment of Kaposi sarcoma among individuals with or without HIV infection. Clin Cancer Res. 2022 Mar 1;28(5):840-50.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898289
http://www.ncbi.nlm.nih.gov/pubmed/34862247?tool=bestpractice.com
Patients taking pomalidomide or lenalidomide must follow strict contraceptive practices as these agents are teratogenic. In the US, patients and medical staff must adhere to a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the medication outweigh its risks.
Therapeutic agents that may be useful as further options in the refractory/relapsed setting include:[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
[69]Schwartsmann G, Sprinz E, Kromfield M, et al. Clinical and pharmacokinetic study of oral etoposide in patients with AIDS-related Kaposi's sarcoma with no prior exposure to cytotoxic therapy. J Clin Oncol. 1997 May;15(5):2118-24.
http://www.ncbi.nlm.nih.gov/pubmed/9164226?tool=bestpractice.com
[70]Tas F, Sen F, Keskin S, et al. Oral etoposide as first-line therapy in the treatment of patients with advanced classic Kaposi's sarcoma (CKS): a single-arm trial (oral etoposide in CKS). J Eur Acad Dermatol Venereol. 2013 Jun;27(6):789-92.
http://www.ncbi.nlm.nih.gov/pubmed/22188463?tool=bestpractice.com
[71]Hosseinipour MC, Kang M, Krown SE, et al; A5264/AMC-067 REACT-KS Team. As-needed vs immediate etoposide chemotherapy in combination with antiretroviral therapy for mild-to-moderate AIDS-associated Kaposi sarcoma in resource-limited settings: A5264/AMC-067 Randomized Clinical Trial. Clin Infect Dis. 2018 Jul 2;67(2):251-60.
https://academic.oup.com/cid/article/67/2/251/4819203
http://www.ncbi.nlm.nih.gov/pubmed/29365083?tool=bestpractice.com
[72]Wang X, Bao Z, Zhang X, et al. Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis. Oncotarget. 2017 May 31;8(35):59901-14.
https://www.oncotarget.com/article/18316/text
http://www.ncbi.nlm.nih.gov/pubmed/28938692?tool=bestpractice.com
[73]Delyon J, Biard L, Renaud M, et al. PD-1 blockade with pembrolizumab in classic or endemic Kaposi's sarcoma: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2022 Apr;23(4):491-500.
http://www.ncbi.nlm.nih.gov/pubmed/35279271?tool=bestpractice.com
[74]Zer A, Icht O, Yosef L, et al. Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). Ann Oncol. 2022 Jul;33(7):720-7.
http://www.ncbi.nlm.nih.gov/pubmed/35339649?tool=bestpractice.com
[75]Koon HB, Krown SE, Lee JY, et al. Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol. 2014 Feb 10;32(5):402-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912327
http://www.ncbi.nlm.nih.gov/pubmed/24378417?tool=bestpractice.com
Etoposide
Imatinib (a tyrosine kinase inhibitor)
Nivolumab (an antiprogrammed death-1 [anti-PD-1] monoclonal antibody immune checkpoint inhibitor) with or without ipilimumab (an anti-cytotoxic T lymphocyte-associated protein-4 [CTLA-4] monoclonal antibody immune checkpoint inhibitor)
Pembrolizumab (an anti-PD-1 monoclonal antibody immune checkpoint inhibitor).
Immune checkpoint inhibitors should not be used in patients with concomitant multicentric Castleman disease (MCD) or KS inflammatory cytokine syndrome because of the risk of exacerbation. Consider additional monitoring if using immune checkpoint inhibitors in patients with a history of Kaposi sarcoma-associated herpesvirus (KSHV)-associated diseases.[2]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Kaposi sarcoma [internet publication].
https://www.nccn.org/guidelines/category_1
See Complications.