As-Needed versus Immediate Etoposide Chemotherapy in Combination with Antiretroviral Therapy for Mild or Moderate AIDS-associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial.

TitleAs-Needed versus Immediate Etoposide Chemotherapy in Combination with Antiretroviral Therapy for Mild or Moderate AIDS-associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial.
Publication TypeJournal Article
Year of Publication2018
AuthorsHosseinipour MC, Kang M, Krown SE, Bukuru A, Umbleja T, Martin J, Orem J, Godfrey C, Hoagland B, Mwelase N, Langat D, Nyirenda M, MacRae J, Borok-Williams M, Samaneka W, Moses A, Mngqbisa R, Busakhala N, Martínez-Maza O, Ambinder R, Dittmer DP, Nokta M, Campbell TB
Corporate AuthorsA5264/AMC-067 REACT-KS team
JournalClin Infect Dis
Date Published2018 Jan 22
ISSN1537-6591
Abstract

Background: Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate versus as-needed oral etoposide (ET) among HIV-infected individuals with mild-to-moderate KS initiating ART.

Methods: Chemotherapy-naïve, HIV-1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (TDF/FTC/EFV) alone (chemotherapy "As-Needed" arm) vs ART plus up to 8 cycles of oral ET (Immediate arm). Participants with KS progression on ART alone received ET as part of the As-Needed strategy. Primary outcome was ordinal: failure (composite of KS progression, initiation of non-study chemotherapy, lost-to-follow-up, death), stable, and response at 48 weeks. Secondary outcomes included times to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response.

Results: Of 190 randomized participants (As-Needed=94, Immediate=96), the majority were men (71%) and African (93%); the median age was 34 years. Failure (53.8% vs 56.6%), Stable (16.3% vs 10.8%) and Response (30% vs 32.5%) did not differ between arms (As-Needed vs Immediate) among those with Week 48 data potential (N=163, p=0.91). Times to KS progression (p=0.021), KS-IRIS (p=0.003), and KS response (p=0.003) favored the Immediate arm. 25 participants died (13%). Mortality, adverse events, CD4+ T-cell changes and HIV RNA suppression were similar at 48 weeks.

Conclusion: Among HIV-infected adults initiating ART for mild-to-moderate KS, immediate ET provided early, non-durable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low.

ClinicalTrials.gov: NCT01352117 (https://clinicaltrials.gov/ct2/show/NCT01352117?term=NCT01352117&rank=1).

DOI10.1093/cid/ciy044
Alternate JournalClin. Infect. Dis.
PubMed ID29365083