Phase II Trial of Imatinib in AIDS-Associated Kaposi's Sarcoma: AIDS Malignancy Consortium Protocol 042

• Published in: Journal of clinical oncology Vol. 32; no. 5; pp. 402 - 408
• Main Authors: KOON, Henry B, KROWN, Susan E, NOY, Ariela, LEE, Jeannette Y, HONDA, Kord, RAPISUWON, Suthee, ZHENGHE WANG, ABOULAFIA, David, REID, Erin G, RUDEK, Michelle A, DEZUBE, Bruce J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10-02-2014
• Subjects: Adult; Aged; AIDS-Related Opportunistic Infections - blood; AIDS-Related Opportunistic Infections - drug therapy; AIDS-Related Opportunistic Infections - enzymology; AIDS-Related Opportunistic Infections - genetics; AIDS-Related Opportunistic Infections - pathology; Anti-HIV Agents - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Benzamides - adverse effects; Benzamides - pharmacokinetics; Benzamides - therapeutic use; Biological and medical sciences; Cytokines - blood; Disease Progression; Female; Human viral diseases; Humans; Imatinib Mesylate; Infectious diseases; Male; Medical sciences; Middle Aged; Molecular Targeted Therapy; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Nmel; ORIGINAL REPORTS; Pilot Projects; Piperazines - adverse effects; Piperazines - pharmacokinetics; Piperazines - therapeutic use; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins c-kit - antagonists & inhibitors; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Pyrimidines - adverse effects; Pyrimidines - pharmacokinetics; Pyrimidines - therapeutic use; Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors; Receptor, Platelet-Derived Growth Factor beta - genetics; Receptor, Platelet-Derived Growth Factor beta - metabolism; Sarcoma, Kaposi - blood; Sarcoma, Kaposi - drug therapy; Sarcoma, Kaposi - enzymology; Sarcoma, Kaposi - genetics; Sarcoma, Kaposi - pathology; Time Factors; Treatment Outcome; Tumors; United States; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; United States; Antineoplastic agent; Immunopathology; Skin disease; Imatinib; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; AIDS; Malignancy; Malignant tumor; Immune deficiency; Infection; Kaposi sarcoma; Cancerology; Viral disease; Phase II trial; Protein-tyrosine kinase; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.48.6365

Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients.
This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable.
Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines.
Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.