Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection: The Phase 2 DURVAST Study

Abstract

Importance: Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1-infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies.

Objective: To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection.

Design, setting, and participants: The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti-PD-1 or anti-PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy.

Interventions: Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects.

Main outcomes and measures: Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1.

Results: A total of 20 HIV-1-infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study.

Conclusions and relevance: Durvalumab treatment was feasible and safe in HIV-1-infected patients with cancer receiving combination antiretroviral therapy. HIV-1-infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments.

Trial registration: ClinicalTrials.gov Identifier: NCT03094286.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Gonzalez-Cao reported receiving grants from AstraZeneca Spain during the conduct of the study and personal fees from AstraZeneca, Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Pierre Fabre, and Takeda outside the submitted work. Dr Morán reported receiving travel expenses from AstraZeneca and travel expenses and advisory board fees from Roche and Boehringer Ingelheim outside the submitted work. Dr Dalmau reported receiving grants from AstraZeneca Farmacéutica Spain during the conduct of the study. Dr Juan reported receiving honoraria and advisory fees from AstraZeneca, Roche, Boehringer Ingelheim, Bristol-Myers Squibb, and Merck Sharp & Dohme, and advisory fees from Eli Lilly and Company and Pfizer outside the submitted work. Dr de Castro reported receiving personal fees and nonfinancial support from AstraZeneca, Hoffmann-La Roche, Merck Sharp & Dohme, and Bristol-Myers Squibb outside the submitted work. Dr R. Blanco reported receiving personal fees and nonfinancial support from Merck Sharp & Dohme and personal fees from Boehringer Ingelheim, Roche, AstraZeneca, and Bristol-Myers Squibb outside the submitted work. Dr J. Blanco reported receiving personal fees from AlbaJuna Therapeutics and institutional grants from Merck Sharp & Dohme and HIPRA outside the submitted work. Dr Prado reported receiving grants from AstraZeneca during the conduct of the study. Dr Clotet reported receiving grants from AstraZeneca during the conduct of the study and personal fees from Aelix Therapeutics, AlbaJuna Therapeutics, and Merck Sharp & Dohme outside the submitted work. Dr Massuti reported receiving grants from Servier and AstraZeneca, grants and personal fees from Roche and Merck Sharp & Dohme, and personal fees from Bristol-Myers Squibb, Takeda, Pfizer, and Boehringer Ingelheim outside the submitted work. Dr Provencio reported receiving grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, and Takeda outside the submitted work. Dr Huang reported receiving nonfinancial support (supplied reagents) from NanoString Technologies outside the submitted work. Dr Martinez-Picado reported receiving institutional grants from AstraZeneca during the conduct of the study; institutional grants from Grifols; institutional grants and educational/consultancy fees from Gilead, Merck Sharp & Dohme, and ViiV Healthcare; and educational/consultancy fees from Janssen outside the submitted work. No other disclosures were reported.

Figures

Figure.. T-cell Count and Plasma Viremia

There were no significant changes in CD4+ T-cell counts (A), CD8+ T-cell counts (B), or plasma viral load (C) when comparing pretreatment samples with last samples after treatment. D, Four patients achieved a partial response (dark blue lines); 5 patients achieved stable disease (orange lines) that in 4 cases continued for more than 24 weeks; and 7 patients had progressive disease (light blue lines) as their best response. IQR indicates interquartile range.