1. In this randomized controlled trial, adjuvant therapy with durvalumab led to improved overall and progression-free survival compared to placebo in patients with limited-stage small cell lung cancer (SCLC).
2. Durvalumab had a tolerable safety profile, with a comparable incidence of adverse effects to the placebo group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Small cell lung cancer is an aggressive form of cancer, in which one-third of patients present with limited-stage disease. The longest survival is achieved with concurrent chemoradiotherapy. These patients, however, often have disease relapse within two years and have limited five-year survival. Advances in systemic treatment for limited-stage SCLC have not progressed over the decades. However, more recent studies have suggested that adjuvant therapy with a high-affinity human IgG1 monoclonal antibody, called durvalumab, that binds programmed death ligand 1 could help prolong disease-free survival in patients with non-small cell lunger cancer who have undergone concurrent chemoradiotherapy. This randomized controlled trial evaluated the efficacy and safety of durvalumab, with or without tremelimumab—a monoclonal antibody targeting the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitory receptor on T cells—as adjuvant therapy in patients with limited-stage SCLC who remained progression-free following chemoradiotherapy. Patients were randomized to receive durvalumab, durvalumab plus tremelimumab, or a placebo. Durvalumab significantly improved overall survival and progression-free survival compared to placebo. The incidence of adverse effects in patients treated with durvalumab was comparable to those receiving placebo, indicating a tolerable safety profile. However, limitations of the study include insufficient statistical power for subgroup analyses and the underrepresentation of Black patients.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: This phase three randomized controlled trial assessed whether durvalumab, with or without tremelimumab, improved survival outcomes in patients with limited-stage SCLC after standard chemoradiotherapy. Adult patients with histologically or cytologically documented limited-stage SCLC who had not had progression after definitive chemoradiotherapy and who had a World Health Organization performance status score of zero or one were eligible. Patients with a history of pneumonitis of grade two or higher or with unresolved toxic effects of chemoradiotherapy were excluded from participation. A total of 730 patients were randomly assigned in a 1:1:1 ratio to either the durvalumab group that received 1500mg of durvalumab plus tremelimumab-matched placebo every 4 weeks for 4 doses (n=264), the durvalumab-tremelimumab group that received 1500mg of durvalumab plus 75mg of tremelimumab every 4 weeks for 4 doses (n=200), or the placebo group that received durvalumab-matched placebo plus tremelimumab-matched placebo every 4 weeks for 4 doses (n=266). The two primary outcomes were overall survival and progression-free survival when comparing the durvalumab group to the placebo group. Results from this trial found that durvalumab therapy led to significantly longer overall survival than placebo. Durvalumab also resulted in significantly longer progression-free survival. The incidence of adverse events was 24.4% in the durvalumab group and 24.2% in the placebo group. Overall, results from this randomized controlled trial found that adjuvant therapy with durvalumab resulted in significantly longer overall and progression-free survival compared to placebo in patients with limited SCLC after standard chemoradiotherapy. Durvalumab was also found to have a tolerable safety profile.
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