Durvalumab Shows Improvements in Overall Survival, Progression-Free Survival for Small Cell Lung Cancer
Both dual primary endpoints—progression-free survival and overall survival—were met with durvalumab.
AstraZeneca has announced positive results from the ADRIATIC phase 3 trial that assessed durvalumab (Imfinzi) compared to placebo among individuals with limited-stage small cell lung cancer (LS-SCLC). The outcomes displayed statically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) in patients with LS-SCLC that has not advanced after concurrent chemoradiotherapy (cCRT), according to study authors.
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“Many patients treated for limited-stage small cell lung cancer face disease recurrence and the standard of care has remained unchanged for decades. ADRIATIC is the first global phase 3 immunotherapy trial to deliver significant, clinically meaningful improvement in survival in this setting, marking a breakthrough for patients with this devastating disease,” said Suresh Senan, PhD, Professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Center in the Netherlands, and principal investigator, in a press release.
Lung cancer makes up around one-fifth of all cancer deaths and 15% of cases are SCLC. SCLC is an aggressive type of lung cancer that recurs and results in rapid progression, even after chemotherapy and radiotherapy, commonly impacting individuals with LS-SCLC. However, LS-SCLC impacts 30% of SCLC diagnoses with limited prognosis despite cCRT treatment. The study authors noted that the survival rate is low for these individuals, with just 15% to 30% of patients surpassing 5 years of survival following the diagnosis.
Durvalumab could offer further treatments for individuals with LS-SCLC as a human monoclonal antibody that binds to the PD-L1 protein, preventing PD-L1 from interacting with PD-1 and CD80 proteins, according to study authors. This blockage aims to counter the tumor’s immune-evading strategies and provide better immune response.
In the randomized, double-blind, placebo-controlled, multi-center global phase 3 ADRIATIC trial, the researchers evaluated durvalumab alone and with tremelimumab (Imjudo; AstraZeneca)—a monoclonal antibody that targets action of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Both therapies were compared to a placebo among a total of 730 individuals from 164 centers in 19 countries, with LS-SCLC that had developed following cCRT.
The study authors noted that the individuals were randomly assigned to receive 1500 mg of durvalumab with or without 75 mg of tremelimumab, every 4 weeks for 4 doses/cycles each, then continued with tremelimumab every 4 weeks for 24 months. The study had dual primary endpoints of PFS and OS for durvalumab compared with the placebo, and both were met.
“These exciting results build on the transformative efficacy of Imfinzi in extensive-stage small cell lung cancer and demonstrate the potential to bring a curative-intent immunotherapy treatment to this earlier-stage setting of small cell lung cancer for the first time. These data, together with the PACIFIC data in unresectable, stage 3 non-small cell lung cancer, underscore the pioneering role of Imfinzi in the treatment of early lung cancer following chemoradiotherapy,” said Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, in a press release.
The study authors noted that no new safety signals were found for durvalumab in this phase 3 trial. However, the efficacy of durvalumab with tremelimumab as a secondary endpoint has not yet been released.
