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. 2019 Jul 15;25(14):4238-4247.
doi: 10.1158/1078-0432.CCR-18-3528. Epub 2019 Apr 12.

A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Ramya Ramaswami #  1 , Thomas S Uldrick #  2 , Mark N Polizzotto  2 , Kathleen M Wyvill  2 , Priscila Goncalves  2 , Anaida Widell  2 , Kathryn Lurain  2 , Seth M Steinberg  3 , William Douglas Figg  4 , Giovanna Tosato  5 , Denise Whitby  6 , Robert Yarchoan  2
Affiliations

A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Ramya Ramaswami et al. Clin Cancer Res. .

Abstract

Purpose: VEGF-A is important in the pathogenesis of Kaposi sarcoma, and bevacizumab has a response rate of 31%. We explored the combination of bevacizumab with liposomal doxorubicin in patients with Kaposi sarcoma.

Patients and methods: Patients with Kaposi sarcoma requiring systemic therapy were enrolled in one of two cohorts. Cohort 1 included patients with human immunodeficiency virus (HIV)-negative Kaposi sarcoma or with HIV-associated Kaposi sarcoma who would not be expected to respond to antiretroviral therapy (ART) alone (i.e., either stable or progressive Kaposi sarcoma on ART). Cohort 2 included all other patients with HIV-associated Kaposi sarcoma. Patients were treated with six cycles of liposomal doxorubicin with bevacizumab every 3 weeks followed by up to 11 cycles of bevacizumab alone.

Results: Sixteen patients were enrolled: 10 (two HIV negative) in cohort 1 and six in cohort 2. Fourteen patients had advanced disease (AIDS Clinical Trials Group T1). Overall response rate (complete and partial responses) was 56% [80% confidence interval (CI), 38%-74%] for all patients and were similar in the two cohorts. Median progression-free survival was 6.9 months (95% CI, 4.5 months-not estimable). Grade 3 and 4 adverse events attributed to therapy included hypertension (n = 5), neutropenia (n = 6), gastrointestinal hemorrhage (n = 1), and cerebral ischemia (n = 1). There was a significant decrease in VEGF-A levels from baseline to the end of six cycles of combination therapy.

Conclusions: Pegylated liposomal doxorubicin in combination with bevacizumab has activity in advanced Kaposi sarcoma, but it is unclear whether the combination yields better outcomes than liposomal doxorubicin used alone.

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Conflict of interest statement

Conflicts of interests:

Drs. Uldrick, Polizzotto, Yarchoan and Whitby are co-inventors on US Patent 10,001,483 entitled “Methods for the treatment of Kaposi’s sarcoma or KSHV-induced lymphoma using immunomodulatory compounds, and uses of biomarkers”. The patent application for this was filed in part based on the results of NCI protocol 12-C-0047, entitled “ A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals with or without HIV” Dr Yarchoan’s understanding that foreign patents have also been filed for this invention. . He is also a co-inventor on other patents not related to the manuscript. These inventions were all made as a full-time employee of the US government under 45 Code of Federal Regulations Part 7. Dr. Tosato, who is also a US Government employee, has a patent on KSHV viral IL-6. All rights, title, and interest to these patents have been or should by law be assigned to the U.S. Department of Health and Human Services. The government conveys a portion of the royalties it receives to its employee inventors under the Federal Technology Transfer Act of 1986 (P.L. 99–502).

Figures

Figure 1:
Figure 1:
Representative photographs of a patient treated in cohort 2. A and B are images of cutaneous KS at study entry, and C and D are images of the same areas following 6 cycles of liposomal doxorubicin and bevacizumab. The patient received 3 cycles of bevacizumab maintenance but had progression. He then received 6 additional cycles of combination therapy and 5 cycles of bevacizumab alone and had a partial response as noted in E and F (taken at week 63 at the end of treatment). At follow up at 3 years and 10 months (week 200), the patient had no visible KS lesions and a biopsy confirmed complete response. The patient did not receive any other therapies for his KS during the follow-up period.
Figure 2:
Figure 2:
Kaplan-Meier curve of progression-free survival in 16 patients treated with bevacizumab in combination with liposomal doxorubicin (6 cycles completed at 4.5 months) followed by bevacizumab monotherapy. Median time to progression from best response was 6.9 months. Hatch marks denote time that patients are censored. It should be noted that patients were censored if they restarted combination therapy without meeting criteria for progression.
See this image and copyright information in PMC

References

    1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266(5192):1865. - PubMed
    1. Moore PS, Kingsley LA, Holmberg SD, Spira T, Gupta P, Hoover DR, et al. Kaposi’s sarcoma-associated herpesvirus infection prior to onset of Kaposi’s sarcoma. AIDS. 1996;10(2):175–80. - PubMed
    1. Yarchoan R, Uldrick TS. HIV-Associated Cancers and Related Diseases. New England Journal of Medicine. 2018;378(11):1029–41. - PMC - PubMed
    1. Chokunonga E, Levy LM, Bassett MT, Borok MZ, Mauchaza BG, Chirenje MZ, et al. Aids and cancer in Africa: the evolving epidemic in Zimbabwe. AIDS. 1999;13(18):2583–8. - PubMed
    1. Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103(9):753–62. - PMC - PubMed

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