Durvalumab feasible, safe for HIV-1-infected patients with cancer
Durvalumab appeared feasible and safe for patients with cancer and HIV-1 infection who receive combination antiretroviral therapy, according to results of a single-arm phase 2 study published in JAMA Oncology.
“Individuals with HIV-1 infection have chronic antigenic immune stimulation and inflammation, even with low plasma HIV-1 RNA levels and preserved CD4+ counts, which contributes to increased incidence of non-AIDS defining cancers,” Maria Gonzalez-Cao, MD, PhD, researcher in the department of medical oncology at Hospital Universitario Quirón Dexeus in Barcelona, Spain, and colleagues wrote. “Non-small cell lung cancer is now the leading cause of cancer deaths [among] individuals receiving effective combination antiretroviral therapy.”
Therapies targeting PD-1 or PD-L1, such as the humanized monoclonal antibody durvalumab (Imfinzi, AstraZeneca), have been effective in NSCLC and across many other tumor types. However, patients with HIV-1 infection often are excluded from cancer immunotherapy clinical trials due to safety and feasibility concerns.
“PD-1 receptor confers a selective advantage for latently infected cells persisting during [combination antiretroviral therapy] and provides a rationale for the assessment of immune checkpoint inhibitor therapy in HIV-1-infected persons with cancer,” Gonzalez-Cao and colleagues wrote.
The researchers evaluated the feasibility and safety of IV durvalumab, dosed at 1,500 mg every 4 weeks and administered until disease progression or unacceptable toxicity, among 20 patients (median age, 54 years; range, 30-73; 80% men) with advanced solid tumors and virologically controlled HIV-1 infection.
All patients had basal undetectable plasma viremia while receiving combination antiretroviral therapy. Twelve patients (60%) had experienced disease progression after previous treatment for cancer.
Researchers graded adverse events using NCI Common Terminology Criteria for Adverse Events version 4.03 and evaluated tumor response using Response Evaluation Criteria in Solid Tumors version 1.1.
Results showed that, after a median four cycles of durvalumab, 50% of patients experienced grade 1 and grade 2 drug-related adverse events, including diarrhea, asthenia and arthromyalgia. Researchers observed no grade 3 or grade 4 drug-related adverse events. Four of 16 response-evaluable patients achieved partial response and five had stable disease, including four with durable stable disease, for a disease control rate of 50%. CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study, according to the researchers.
The study’s small sample size served as a limitation.
“Our results confirm that treatment with durvalumab is also safe regarding sustained control of HIV-1 infection,” Gonzalez-Cao and colleagues wrote. “All patients continued antiretroviral treatment, and plasma viremia remained undetected.” – by John DeRosier
Disclosures: Gonzalez-Cao reports research funding and personal fees from AstraZeneca and personal fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Roche and Takeda. Please see the study for all other authors’ relevant financial disclosures.