Durvalumab Consolidation Offers New Standard of Care for Limited-Stage SCLC

Several practice-changing abstracts were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, and findings from the ADRIATIC study (NCT03703297) were among them.

The study investigated the use of durvalumab (Imfinzi) as consolidation therapy for patients with limited-stage small cell lung cancer (SCLC) that had not worsened after standard chemoradiotherapy. Patients were randomized to receive either durvalumab with placebo, durvalumab with tremelimumab (Imjudo), or placebo alone.

Compared with placebo, durvalumab significantly improved overall survival (OS) and progression-free survival (PFS) among patients with limited-stage SCLC. Further, the adverse events were similar between the durvalumab and placebo groups.

These findings suggest a promising new treatment option for patients with this disease.

In an interview with Targeted Oncology^TM, David Spigel, MD, chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, who presented findings from the study at ASCO, discussed the implications of this research.

Targeted Oncology: What are some of the unmet needs in this patient population and how did they lead to this study?

Spigel: This study was looking at patients with limited-stage small cell lung cancer. This is something that [we are] seeing at different rates around the world in high smoking areas. It [makes up] about 20% of all lung cancer.In other areas it may be as low as 10%. But the cancers are very aggressive. For most patients, when small cell lung cancer is diagnosed, it has already spread. But about one-third of patients will have small cell lung cancer that still is curable in something we call limited-stage.

The standard of care for many decades has been to give chemotherapy and radiation together for patients with hopefully curable small cell lung cancer. But even with that, most patients will have their cancer return within 2 years, and probably less than one-third will survive beyond 5 years. ADRIATIC was designed to see if immunotherapy—in the case of this analysis, we presented durvalumab, a PD-L1 antibody—can improve how patients did after that standard of chemotherapy and radiation given together.

What were the end points of the study? What was your methodology?

This was a large trial. It was a randomized, phase 3, double-blind, placebo-controlled trial run around the world. The patients were randomized to get durvalumab after chemoradiation, durvalumab, and placebo, or a combination of durvalumab and a CTLA4 antibody, tremelimumab. The analysis we presented [at ASCO] was the first planned interim analysis of the primary end points for durvalumab vs placebo. That analysis had 2 primary end points: overall survival and progression-free survival by blinded independent central review. There are additional analyses planned for the tremelimumab arm, as well as things like quality-of-life and other safety end points. Those will come out, specifically the tremelimumab comparison, with a later interim analysis.

Could you summarize the findings that were presented?

The study met both of its primary end points. Durvalumab improved overall survival with a hazard ratio of 0.73 that corresponds to a 27% reduction in the risk of death compared with placebo. The median survival was improved by approximately 2 years. So, a 22.5-month improvement in median overall survival with durvalumab. [For] the second primary end point, progression-free survival, the hazard ratio for benefit with durvalumab was 0.76, a 24% reduction in the risk of death or progression. That corresponded to an advantage of 7.4 months in median progression-free survival. It was fantastic that both primary end points were met.

One controversial area in the treatment of limited-stage calls small cell lung cancer is prophylactic cranial irradiation, or PCI. In this study, patients were allowed to get it or not get it; it was up to the treating physician and the patient and their family. About half got it, so 54% didn’t get it, but that means nearly half did not get it. It did not seem to matter. The benefits [seen] with durvalumab for OS and PFS did not seem to be contingent on whether [the patient receives] PCI or no PCI. I think that is reassuring for doctors like [me] who favor not giving prophylactic cranial radiation.That benefits still exists.

For clinicians, what would you consider to be the major takeaways from these findings?

I think this establishes a new standard of care for the treatment of limited-stage small cell lung cancer. That is, chemotherapy and radiation should continue to be the core treatment of those patients. But after that is completed and patients are safe, and there are no other issues, they should go on to receive up to 2 years of durvalumab given monthly because of these benefits that have been seen in this study.

Were there any specific safety signals or notable adverse events identified?

The expected safety issue was related to the radiation chemotherapy components. About 23% of patients in each arm had radiation pneumonitis. If you looked at [adverse] effects that seemed to be related only to durvalumab, those were not unusual. There was a little bit of extra pneumonitis, skin, and thyroid related disorders, but those were mostly low-grade, and nothing really different from what is already been experienced, and doctors are used to managing [these events] when they treat with durvalumab that is already out there in non–small cell lung cancer and is already being used in extensive-stage small cell lung cancer. Reassuringly, there were no major new safety signals.

REFERENCE:

Spigel D, Cheng Y, Cho B, et al. ADRIATIC: durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol 42, 2024 (suppl 17; abstr LBA5) doi:10.1200/JCO.2024.42.17_suppl.LBA5