A clinical trial funded by the National Institute of Allergy and Infectious Diseases (NIAID) and National Cancer Institute comparing three chemotherapy regimens in combination with antiretroviral treatment (ART) for treatment of advanced AIDS-Kaposi’s sarcoma patients in Africa and South America has ended early. Interim data showed that participants who were treated with paclitaxel plus ART had better tumor outcomes than participants who received the other treatment regimens.
Kaposi sarcoma (KS) is a cancer that causes abnormal tissue to grow in the skin, the lining of the mouth and throat, lymph nodes, and the lungs and other internal organs. KS occurs most often in people living with HIV whose immune systems have become weak and is particularly common in low- and middle-income countries. The disease is caused by a virus called Kaposi sarcoma associated herpesvirus (KSHV), or human herpesvirus-8. Infection with KSHV is common in some areas of the world, particularly in sub-Saharan Africa, where there were high rates of KS even before the AIDS epidemic. KS is one of the most common cancers occurring in people living with HIV.
Thanks to the availability of ART, the number of KS cases has fallen dramatically in North America and Europe. However, KS remains common in other parts of the world where ART availability and accessibility may be less comprehensive. This prevalence makes the study of KS critical to improving AIDS survival rates and informing the knowledge base for HIV and cancer research.
The randomized, Phase 3 trial had enrolled 334 men and women in six countries in South America and Africa since it began in October 2013; it was conducted by the AIDS Clinical Trial Group with the AIDS Malignancy Consortium. The trial originally compared the clinical efficacy of intravenously administered paclitaxel plus ART with either intravenously delivered bleomycin and vincristine (BV) with ART or orally administered etoposide with ART for the initial treatment of advanced stage AIDS-KS. The etoposide arm was discontinued in 2016 when it was found that the drug was inferior to paclitaxel. Etoposide is a treatment that does not require specialized chemotherapy administration facilities like the other two regimens being tested. Paclitaxel plus ART is a standard treatment in the United States, while BV with ART is currently a standard treatment in many developing countries.
The decision to close the trial was made following a March 13, 2018, recommendation to NIAID by the study’s Data and Safety Monitoring Board (DSMB), an independent group composed of clinical research experts, statisticians, ethicists and community representatives that meets at regular intervals throughout a study to review its safety and efficacy data.
The DSMB found that trial participants randomized to the paclitaxel study arm had lower tumor progression rates and higher rates of progression-free survival than participants randomized to the BV arm after 48 weeks of treatment. The DSMB recommended that the study end now because the conclusions that can be drawn about the two different drug regimens are unlikely to change even if the study continued until its planned conclusion.
Participants, site investigators, institutional review boards and regulatory agencies are being notified of the DSMB recommendations and changes to the study. For more information on this trial, visit ClinicalTrials.gov.