Summary

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• This summary is based on the review of 42 systematic reviews/meta-analyses. ^[1-42]
• Overall Survival (OS): Durvalumab improves OS in stage III Non-Small Cell Lung Cancer (NSCLC) following Chemoradiotherapy (CRT) (Hazard Ratio [HR]: 0.73; 95% Confidence Interval [CI]: 0.61–0.87) and advanced/metastatic NSCLC (HR: 0.62; 95% CI: 0.52–0.75). Combining durvalumab with chemotherapy improves OS in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (HR: 0.80; 95% CI: 0.72–0.85), endometrial cancer (notably in Deficient Mismatch Repair [dMMR] subgroups), and biliary tract cancer (mean OS difference at 24 months by Restricted Mean Survival Time [RMST]: 1.21 months).
• Progression-Free Survival (PFS): Durvalumab improves PFS in stage III NSCLC (HR: 0.71; 95% CI: 0.54–0.95) and advanced/metastatic NSCLC (HR: 0.57; 95% CI: 0.48–0.67). PFS benefits are also observed in ES-SCLC (HR: 0.72; 95% CI: 0.63–0.83), endometrial cancer (especially in dMMR subgroups), and biliary tract cancer with immunotherapy-based regimens.
• Objective Response Rate (ORR): Durvalumab increases ORR in Blood Tumor Mutation Burden (bTMB)-high NSCLC patients (Odds Ratio [OR]: 2.69; 95% CI: 1.84–3.93) and in dMMR endometrial cancer when combined with chemotherapy. Improved ORR is also noted with pembrolizumab and chemotherapy in Triple-Negative Breast Cancer (TNBC).
• Comparative Effectiveness: Durvalumab combined with chemotherapy demonstrates greater OS and PFS benefits compared to chemotherapy alone across cancers. In NSCLC, durvalumab has comparable efficacy to other Programmed Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) inhibitors, such as atezolizumab.
• In stage III NSCLC, durvalumab following CRT showed grade ≥3 pneumonitis rates of 5.36% and any-grade pneumonitis incidence at 27%. Older patients with NSCLC had higher rates of pneumonia and lower immunotherapy completion rates.
• Durvalumab in combination with chemotherapy for ES-SCLC and endometrial cancer resulted in more frequent any-grade and grade ≥3 Adverse Events (AEs) compared to chemotherapy alone, with common Immune-Related Adverse Events (irAEs) such as rash, hyperthyroidism, and increased Aspartate Aminotransferase (AST) levels.
• Combination therapies, such as durvalumab with tremelimumab, were associated with higher rates of severe AEs compared to monotherapy, including gastrointestinal issues (e.g., diarrhea, colitis) and endocrinopathies (e.g., hyperthyroidism, hypothyroidism).
• Patients with high tumor mutation burden (bTMB) in NSCLC show greater benefit from PD-1/PD-L1 inhibitors, including improved objective response rates (OR: 2.69; 95% CI: 1.84–3.93), while dMMR endometrial cancer patients experience more pronounced benefits in OS and PFS with durvalumab. ES-SCLC patients, regardless of age, gender, or performance status, benefit from adding Immune Checkpoint Inhibitors (ICIs) to chemotherapy.