Small-cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for approximately 15% of all lung cancer cases.¹ LS-SCLC, which is SCLC confined to one lung or one side of the chest, accounts for approximately 30% of SCLC diagnoses.² Despite initial responsiveness to standard chemoradiotherapy, the prognosis for LS-SCLC remains poor, with only 15%-30% of patients surviving five years post-diagnosis.³ The rapid recurrence and progression of the disease highlight the urgent need for effective adjuvant therapies.³

Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80 proteins.⁴ This mechanism counteracts the tumor's immune-evading tactics, releasing the inhibition of immune responses and enabling the immune system to recognize and attack cancer cells more effectively.⁴ By enhancing the body's natural immune response, durvalumab offers a promising therapeutic approach for patients with LS-SCLC.¹

ADRIATIC is a phase 3, double-blind, randomized, placebo-controlled study that evaluated durvalumab as monotherapy and in combination with tremelimumab in patients with LS-SCLC who had not progressed after concurrent platinum-based chemoradiotherapy.¹ The trial enrolled 730 patients across 164 centers in 19 countries, with participants randomized 1:1:1 to receive durvalumab monotherapy (1,500mg every 4 weeks) (n=264), durvalumab + tremelimumab (75mg every 4 weeks for 4 doses, then 1,500mg durvalumab every 4 weeks) (n=200), or placebo (n=266).¹ The treatment period continued for up to 24 months of treatment.¹ Results of the first planned interim analysis of the primary endpoints, overall survival (OS) and progression-free survival (PFS) for durvalumab monotherapy compared to placebo have been reported.¹

The results demonstrated a significant improvement in the OS and PFS of patients treated with durvalumab monotherapy.¹ The median OS was 55.9 months in the durvalumab group compared to 33.4 months in the placebo group, representing a 27% reduction in the risk of death (HR=0.73; 98.321% CI: 0.54-0.98; p=0.01).¹ Additionally, the median PFS was 16.6 months for durvalumab vs. 9.2 months for placebo (HR=0.76; 99.816% CI: 0.59-0.98; p=0.02).¹ These findings underscore the potential of durvalumab in extending survival and delaying disease progression in patients with LS-SCLC.¹

The safety profile of durvalumab in the ADRIATIC trial was consistent with its known safety profile.¹ No new safety signals were identified.¹ The incidence of grade 3 or 4 adverse events was 24.4% and 24.2% in the durvalumab and placebo groups, respectively.¹ Adverse events leading to discontinuation occurred in 16.4% of patients treated with durvalumab monotherapy and 10.6% of those treated with placebo.¹ Grade 3 or 4 pneumonitis or radiation pneumonitis was observed in 3.1% of those treated with durvalumab and 2.6% of those treated with placebo.¹ These results suggest that durvalumab is generally well-tolerated and has manageable side effects.¹

In conclusion, findings demonstrated that adjuvant therapy with durvalumab offers promising efficacy and a manageable safety profile for patients with LS-SCLC after chemoradiotherapy.¹ Durvalumab significantly enhanced OS and PFS compared to placebo, indicating its potential to improve clinical outcomes in this challenging patient population.¹ With a safety profile that aligns with expectations for immunotherapy, durvalumab represents a valuable addition to the therapeutic landscape for LS-SCLC.5