David Spigel, MD, Sarah Cannon Research Institute, Nashville, Tennessee, discusses results from the phase 3 ADRIATIC study, evaluating durvalumab with or without tremelimumab as consolidation therapy for patients with limited-stage small-cell lung cancer (LS-SCLC) who had not progressed following concurrent platinum-based chemoradiotherapy.

This interim analysis found that durvalumab as consolidation therapy improved overall survival and progression-free survival to a statistically significant and clinically meaningful degree. Dr Spigel concluded, “This would be a new standard of care in the treatment of limited-stage small-cell lung cancer, a welcome and big advance for our patients.”

Transcript:

David Spigel, I'm the Chief Scientific Officer at Sarah Cannon Research Institute in Nashville, Tennessee. ADRIATIC was a phase 3 study designed to assess the role of immunotherapy as consolidation following concurrent chemoradiation in the treatment of limited-stage small-cell lung cancer.

There really haven't been any major advances in the treatment of limited-stage small-cell lung cancer in several decades. The standard of care is concurrent platinum-based chemoradiotherapy. Despite that, most patients will have cancer come back in the first 2 years and about one-third of patients will survive 5 years.

ADRIATIC was designed to assess the role of immunotherapy in the form of durvalumab, a PD-L1 antibody —there was also an arm that included plus/minus with tremelimumab, a CTLA-4 antibody— to be used as consolidation following concurrent chemoradiation. All the patients had to have limited-stage small-cell lung cancer, and all the patients had good performance status, and all the patients had to have received concurrent chemoradiation therapy before they were randomized on the trial. The chemotherapy was platinum etoposide and the radiation could either have been once daily up to 66 Gray or twice daily up to 45 Gray and the radiation had to commence before the end of the second cycle. 

This was a randomized phase 3, double-blind placebo-controlled, global study and so all the patients were randomized to either durvalumab at 1500 mg IV monthly, placebo, or an arm that included tremelimumab with durvalumab. Stratification was by stage and by PCI-use — PCI is prophylactic cranial irradiation and that was left up to the treating investigator. Patients stayed on therapy until cancer progressed, there was intolerable toxicity, or a maximum of 24 months.

The study had 2 primary endpoints for the analysis of durvalumab versus placebo and those were overall survival and progression-free survival by blinded independent central review. That’s what this presentation was based on, this analysis of durvalumab versus placebo. The analysis of durvalumab with tremelimumab, the CTLA-4 antibody is still blinded and will be part of a future analysis.

What the study found is that durvalumab demonstrated a statistically significant improvement in overall survival with a hazard ratio of 0.73, a 27% reduction in the risk of death, and the median survival in the durvalumab arm was 55.9 months, and in the placebo arm it was 33.4 months — a 22-and-a-half-month improvement in median survival, a major finding. The progression-free survival was also statistically-significantly improved, with a hazard ratio of 0.76, a 24% reduction in the risk of death or progression with durvalumab. And that was about a 7.4-month improvement in median progression-free survival, 16.6 months versus 9.2 months. So, the study hit both end points, overall survival and progression-free survival. 

The study was found to have a great safety profile. There was about 38% of patients had any grade pneumonitis, most of that was radiation-related pneumonitis, in the durvalumab arm, and there was 30% of patients on the placebo arm that had pneumonitis, but it led to very low discontinuation rates or severe problems. There was one grade 5 related event on the durvalumab arm. 

In summary, the use of immunotherapy, durvalumab, as consolidation, following concurrent chemoradiation for limited-stage small-cell lung cancer, showed an improvement in overall survival and progression-free survival and was found to be very safe. This would be a new standard of care in the treatment of limited-stage small-cell lung cancer, a welcome and big advance for our patients.

Source:

Spigel DR, Cheng Y, Cho BC, et al. ADRIATIC: Durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). Presented at 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. doi:10.1200/JCO.2024.42.17_suppl.LBA5