Dr Shields on Key ADRIATIC Trial Data With Adjuvant Durvalumab in LS-SCLC

“More studies are needed to understand this trend [in] improvement [with immunotherapy] in LS-SCLC vs ES-SCLC, [although data still demonstrate the benefit of] immunotherapy in both settings.”

Misty D. Shields, MD, PhD, assistant professor, clinical medicine, Department of Medicine, Division of Hematology/Oncology, Indiana University (IU) School of Medicine; and associate member, Experimental and Developmental Therapeutics, IU Melvin and Bren Simon Comprehensive Cancer Center, discusses the implications of the phase 3 ADRIATIC trial (NCT03703297) investigating adjuvant durvalumab (Imfinzi) vs placebo in patients with limited-stage small cell lung cancer (LS-SCLC).

The international, randomized ADRIATIC trial demonstrated that consolidation durvalumab administered every 4 weeks for a maximum of 2 years following concurrent platinum-based chemoradiotherapy significantly improved progression-free survival (HR, 0.76; 97.195% CI, 0.61-0.95; P = .0161) and overall survival (HR, 0.73; 95% CI, 0.57-0.93; P = .0104) compared with placebo in patients with LS-SCLC. Benefits with durvalumab were observed regardless of whether patients had received prophylactic cranial irradiation and irrespective of prior use of carboplatin and cisplatin, Shields says. However, greater improvements were noted in those who received carboplatin as chemosensitizing therapy during radiation, she explains.

As of December 2024, durvalumab has been FDA approved and is established as the standard of care for the treatment of patients with LS-SCLC whose disease has not progressed after concurrent platinum-based chemoradiotherapy. Notably, the recommended dose of durvalumab is 1500 mg every 4 weeks for patients with a body weight of at least 30 kg and 20 mg/kg every 4 weeks for those with a body weight of less than 30 kg for a maximum of 24 months, or until disease progression or unacceptable toxicity.

However, the underlying mechanisms explaining why immunotherapy demonstrates greater efficacy in LS-SCLC compared with extensive-stage SCLC (ES-SCLC) remain unclear, Shields notes. This represents an unmet translational need, warranting further investigation, she emphasizes. Potential factors include its activity in specific neuroendocrine subtypes (such as inflamed subtypes), abscopal effects of immunotherapy following radiation, or increased neoantigen presentation, she states. Ultimately, though, immunotherapy continues to generate favorable outcomes in both LS-SCLC and ES-SCLC, Shields concludes.