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and Hepatitis.com Coverage of the
XVIII International AIDS Conference (AIDS 2010) July 18 - 23, 2010, Vienna, Austria
Maraviroc (Selzentry) Not Associated with Elevated Cancer Risk in Clinical Development Program
Some non-AIDS-defining malignancies have infectious causes; since maraviroc interferes with CCR5 binding, and CCR5-mediated signaling plays a role in immune surveillance, there is a theoretical concern that maraviroc might increase the risk of infections or cancers. Some early maraviroc study data suggested a potential cancer safety signal, leading investigators to look carefully at cancer rates in larger clinical trials of the drug.
Sharon Walmsley from the University of Toronto and colleagues investigated the incidence of and risk factors for malignancies across trial included in the maraviroc Phase 2b/3 development program.
For this retrospective analysis, researchers collected information about treatment-emergent (occurring while on therapy) malignancies in clinical trials with both treatment-experienced and previously untreated participants, including MOTIVATE 1 and 2, MERIT, and A4001029 (patients with non-CCR5-tropic virus). The analysis included data from the randomized blinded study period, as well as open-label extended follow-up.
Overall, 1499 participants in the development program received maraviroc, contributing 2333 person-years of data (median 82 weeks use). In addition, 361 people received efavirenz (Sustiva) as a comparison first-line drug, contributing 768 person-years of data (median exposure 139 weeks) and 270 treatment-experienced patients received placebo with optimized background therapy, contributing 196 person-years (median exposure 20 weeks).
looked at overall cancer rates, rates of AIDS-defining malignancies
(Kaposi's sarcoma, non-Hodgkin lymphoma, and cervical cancer), and non-AIDS
cancers, including those associated with infectious pathogens (e.g.,
anal cancer caused by human papillomavirus, Hodgkin lymphoma linked
to Epstein-Barr virus, liver cancer due to chronic hepatitis B or C)
and those with no known infectious cause.
In this retrospective analysis of nearly 1500 people, "maraviroc-treated patients had a low incidence of malignancies, regardless of virus tropism or degree of antiretroviral treatment experience," the researchers concluded. "Long-term blinded and open-label treatment with maraviroc did not reveal any increased incidence of malignancies, compared to published rates at 48 weeks."
"The exposure-adjusted incidence of malignancies was generally numerically lower in the maraviroc group compared to placebo or efavirenz," they continued. "Across the 3 cohorts, the incidence of non-AIDS-defining malignancies was generally greater than that of AIDS-defining malignancies."
Investigator affiliations: University of Toronto, Toronto, Canada; University of Miami, Miami, FL; ViiV Healthcare, Research Triangle Park, NC; Pfizer Global Research and Development, New London, CT; Pfizer Inc, New York, NY.