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Study Says Tremelimumab-Durvalumab Combination Could be Effective Against Mesothelioma

A recent study suggests that a new immunotherapy drug combination known as tremelimumab-durvalumab could be effective against mesothelioma.

Manufactured by AstraZeneca, tremelimumab is a human immunoglobulin (Ig) G2 monoclonal antibody directed against the human T-cell receptor protein cytotoxic T-lymphocyte-associated protein 4 (CTLA4), with potential immune checkpoint inhibitory and antineoplastic activities. This immunotherapy drug binds to CTLA4 on activated T-lymphocytes and blocks the binding of the antigen-presenting cell ligands B7-1 (CD80) and B7-2 (CD86) to CTLA4, resulting in inhibition of CTLA4-mediated downregulation of T-cell activation.

This activity promotes the interaction of B7-1 and B7-2 with another T-cell surface receptor protein CD28, and results in a B7-CD28-mediated T-cell activation that is unopposed by CTLA4-mediated inhibition. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system.

According to the study, tremelimumab initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. When combined with durvalumab (brand name Imfinzi), an FDA-approved immunotherapy drug for cancer, patients had a better response.

The study, conducted from Oct 30, 2015, to Oct 12, 2016, consisted of 40 mesothelioma patients. Each participant received at least one dose each of tremelimumab and durvalumab. Patients were followed-up for a median of 19.2 months. Eleven of the 40 patients (28%), had an immune-related objective response (all partial responses; confirmed in ten patients), with a median response duration of 16.1 months

Twenty-six of the 40 patients, a noteworthy 65%, had immune-related disease control and 25 (63%) had disease control. Median immune-related progression-free survival was eight months, median progression-free survival was 5.7 months, and median overall survival was 16.6 months. Baseline tumor PD-L1 expression did not correlate with the proportion of patients who had an immune-related objective response or immune-related disease control, with immune-related progression-free survival, or with overall survival. Thirty of the 40 patients (75%) experienced treatment-related adverse events of any grade, of whom seven (18%) had grade 3–4 treatment-related adverse events. Treatment-related toxicity was generally manageable and reversible with protocol guidelines.

Based on the findings, the study team concluded that the combination of tremelimumab and durvalumab appeared active, with a good safety profile in patients with mesothelioma, warranting further exploration.

If you have been diagnosed with mesothelioma, talk to your doctor about developing immunotherapy treatment combinations such as tremelimumab-durvalumab. Innovative treatments such as this could be helpful in treating your specific type of mesothelioma. Talk to your doctor today.

 

Sources

Calabro, Luana, Aldo Morra, and Diana Giannerelli. "Tremelimumab Combined with Durvalumab in Patients with Mesothelioma (NIBIT-MESO-1): An Open-label, Non-randomised, Phase 2 Study." The Lancet Respiratory Medicine. The Lancet, Elsevier Limited, 14 May 2018. Web. 19 July 2018.

“NCI Drug Dictionary.” National Cancer Institute (NCI). U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH), 2018. Web. 19 July 2018.