Efficacy and safety of combination immunotherapy and targeted therapy as second-line and subsequent treatments for advanced biliary tract cancer: A systematic review and meta-analysis.

BACKGROUND

Biliary tract cancer is a highly dangerous cancer that often results in a poor prognosis for patients, even with significant advancements in treatment options. Recent advancements in targeted therapies and immunotherapy have shown great potential in treating various cancers. This underscores the importance of conducting a detailed review and meta-analysis of these approaches specifically for biliary tract cancer.

METHODS

This meta-analysis included data from randomized clinical trials and cohort studies examining the use of immunotherapy and targeted therapies specifically as second-line treatments for patients diagnosed with biliary tract cancer. A comprehensive andsystematic literature search was conducted across prominent databases, including PubMed, Embase, Cochrane Library, and Web of Science, encompassing publications from the inception of these databases until August 31, 2024. Key outcome measures, such as objective response rate (ORR), DCR, progression-free survival, overall survival, and AEs, were meticulously extracted for analysis.

RESULTS

The findings of this meta-analysis revealed that the ORR across the included studies varied from 4% to 33%, with a combined ORR of 14% (95% confidence interval [CI]: 9%-19%). The pooled DCR was calculated at 68% (95% CI: 53%-77%). Median overall survival was reported as 10.75 months (95% CI: 8.23-13.27 months), while median progression-free survival was 4.39 months (95% CI: 2.73-6.04 months).In terms of AEs, most patients experienced only grade 1 to 2 events, indicating a generally favorable tolerance to treatment. The most commonly reported AEs included fatigue (44%, 95% CI: 31%-58%), hypertension (41%, 95% CI: 28%-55%), and nausea (23%, 95% CI: 18%-29%). Additionally, thrombocytopenia emerged as the most prevalent hematological toxicity, occurring in 31% of patients (95% CI: 23%-39%). Notably, the incidence of ≥grade III AEs was very low, remaining below 14%. Among the most frequent severe AEs were hypertension and elevated aminotransferases, with incidences of 14% and 8%, respectively.

CONCLUSION

This comprehensive meta-analysis highlights the potential role of targeted therapies and immunotherapy in the management of biliary tract cancer, demonstrating promising albeit moderate efficacy. These findings underscore the necessity for further research and clinical trials aimed at optimizing treatment protocols to enhance outcomes for patients afflicted with this challenging malignancy.