As-needed vs immediate etoposide chemotherapy in combination with antiretroviral therapy for mild-to-moderate AIDS-associated kaposi sarcoma in resource-limited settings: A5264/AMC-067 randomized clinical trial

for the A5264/AMC-067 REACT-KS Team

Research output: Contribution to journalArticle

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 vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) 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 as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time 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%). 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 =.91). Time to KS progression (P =.021), KS-IRIS (P =.003), and KS response (P =.003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable 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. Clinical Trials Registration NCT01352117.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalClinical Infectious Diseases
Volume67
Issue number2
DOIs
StatePublished - Jul 2 2018

Fingerprint

Kaposi's Sarcoma
Etoposide
Combination Drug Therapy
Acquired Immunodeficiency Syndrome
Randomized Controlled Trials
Therapeutics
Tenofovir
efavirenz
HIV
Drug Therapy
Immune Reconstitution Inflammatory Syndrome
Mortality
South America
HIV-1
Clinical Trials
RNA
T-Lymphocytes

Keywords

  • antiretroviral therapy
  • chemotherapy
  • etoposide
  • HIV
  • Kaposi sarcoma

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{937672a01a5b4fbc8527c4a93c51134d,
title = "As-needed vs immediate etoposide chemotherapy in combination with antiretroviral therapy for mild-to-moderate AIDS-associated kaposi sarcoma in resource-limited settings: A5264/AMC-067 randomized clinical trial",
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 vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) 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 as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time 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{\%}). 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 =.91). Time to KS progression (P =.021), KS-IRIS (P =.003), and KS response (P =.003) favored the immediate arm. Twenty-five participants died (13{\%}). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable 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. Clinical Trials Registration NCT01352117.",
keywords = "antiretroviral therapy, chemotherapy, etoposide, HIV, Kaposi sarcoma",
author = "{for the A5264/AMC-067 REACT-KS Team} and Hosseinipour, {Mina C.} and Minhee Kang and Krown, {Susan E.} and Aggrey Bukuru and Triin Umbleja and Martin, {Jeffrey N.} and Jackson Orem and Catherine Godfrey and Brenda Hoagland and Noluthando Mwelase and Deborah Langat and Mulinda Nyirenda and John Macrae and Margaret Borok and Wadzanai Samaneka and Agnes Moses and Rosie Mngqbisa and Naftali Busakhala and Otoniel Mart{\'i}nez-Maza and Ambinder, {Richard F} and Dittmer, {Dirk P.} and Mostafa Nokta and Campbell, {Thomas B.}",
year = "2018",
month = "7",
day = "2",
doi = "10.1093/cid/ciy044",
language = "English (US)",
volume = "67",
pages = "251--260",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - As-needed vs immediate etoposide chemotherapy in combination with antiretroviral therapy for mild-to-moderate AIDS-associated kaposi sarcoma in resource-limited settings

T2 - A5264/AMC-067 randomized clinical trial

AU - for the A5264/AMC-067 REACT-KS Team

AU - Hosseinipour, Mina C.

AU - Kang, Minhee

AU - Krown, Susan E.

AU - Bukuru, Aggrey

AU - Umbleja, Triin

AU - Martin, Jeffrey N.

AU - Orem, Jackson

AU - Godfrey, Catherine

AU - Hoagland, Brenda

AU - Mwelase, Noluthando

AU - Langat, Deborah

AU - Nyirenda, Mulinda

AU - Macrae, John

AU - Borok, Margaret

AU - Samaneka, Wadzanai

AU - Moses, Agnes

AU - Mngqbisa, Rosie

AU - Busakhala, Naftali

AU - Martínez-Maza, Otoniel

AU - Ambinder, Richard F

AU - Dittmer, Dirk P.

AU - Nokta, Mostafa

AU - Campbell, Thomas B.

PY - 2018/7/2

Y1 - 2018/7/2

N2 - 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 vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) 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 as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time 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%). 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 =.91). Time to KS progression (P =.021), KS-IRIS (P =.003), and KS response (P =.003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable 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. Clinical Trials Registration NCT01352117.

AB - 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 vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) 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 as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time 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%). 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 =.91). Time to KS progression (P =.021), KS-IRIS (P =.003), and KS response (P =.003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable 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. Clinical Trials Registration NCT01352117.

KW - antiretroviral therapy

KW - chemotherapy

KW - etoposide

KW - HIV

KW - Kaposi sarcoma

UR - http://www.scopus.com/inward/record.url?scp=85051276873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051276873&partnerID=8YFLogxK

U2 - 10.1093/cid/ciy044

DO - 10.1093/cid/ciy044

M3 - Article

C2 - 29365083

AN - SCOPUS:85051276873

VL - 67

SP - 251

EP - 260

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 2

ER -