Paclitaxel Plus ART Best For AIDS-Related Kaposi Sarcoma In Limited-Resource Settings

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Paclitaxel is the optimal chemotherapy regimen for use alongside antiretroviral therapy (ART) for patients with AIDS-related Kaposi sarcoma in low- and middle-income countries, research shows. 

The open-label trial failed to demonstrate noninferiority for oral etoposide or bleomycin plus vincristine compared with paclitaxel when given alongside ART in 334 patients attending one of 11 clinics in Brazil, Kenya, Malawi, South Africa, Uganda and Zimbabwe, the investigators report in The Lancet. 

Susan Krown, from the AIDS Malignancy Consortium in New York, USA, and co-authors explain that both the etoposide and bleomycin–vincristine arms of the study were closed early after the noninferiority margins of 15% were exceeded. 

The etoposide arm was closed after the fourth review, at which time the week 48 progression-free survival (PFS) rate was 50% with paclitaxel versus 20% with etoposide, and the corresponding progression or death rates were 47% and 72%. The median time to progression or death was 58 weeks for paclitaxel versus 28 weeks for etoposide, giving a significant hazard ratio (HR) for death or progression of 1.95 in favour of paclitaxel.  

The bleomycin–vincristine arm of the trial was halted after the seventh review, at which time the 48-week PFS rate was 64% for paclitaxel and 44% for bleomycin–vincristine, with progression or death rates of 33% and 53%, respectively. The median time to progression or death was 84 weeks for paclitaxel and 45 weeks for the chemotherapy combination, giving a significant HR of 1.53 in favour of paclitaxel. 

Paclitaxel plus ART was also associated with “a superior outcome” compared with the other two regimens with regard to overall response rate, response duration, CD4 lymphocyte counts and suppression of HIV viraemia. 

In addition, the paclitaxel regimen had “an acceptable adverse event profile that contradicts commonly held concerns about the ability of people with HIV to tolerate cytotoxic chemotherapy and achieve effective HIV control”, the researchers say. 

Susan Krown et al explain that the oral etoposide and bleomycin–vincristine comparators were chosen because of their availability, cost, adverse events and ease of administration in the limited-resource countries of the study. 

“Making paclitaxel widely available as the initial treatment for advanced AIDS-related Kaposi sarcoma in these settings will require enhancements to the infrastructure and personnel dedicated to cancer care”, the investigators write.

“Analysis of the cost-effectiveness of different Kaposi sarcoma treatments would further inform national strategies”, they comment. 

Reference  

Krown SE, Moser CB, MacPhail P, et al. Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial. Lancet; Advance online publication 5 March 2020. https://doi.org/10.1016/S0140-6736(19)33222-2