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Background: The addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy. Methods: Records were identified through a formal search of PubMed and Web of Science. The TOPAZ-1 and KEYNOTE-966 trials were definitively included. Patient-level overall survival (OS) and progression-free survival (PFS) data were reconstructed and analyzed using a one-stage approach. Results: The immunotherapy plus GP chemotherapy group showed superiority over the GP chemotherapy group (OS: HR 0.83, p < 0.001; PFS: HR 0.88, p = 0.009). The survival outcomes were similar between the durvalumab and pembrolizumab groups (OS: HR 1.02, p = 0.83; PFS: HR 0.95, p = 0.53). In the subgroup analysis, the gemcitabine-maintenance group significantly prolonged the OS compared to the gemcitabine-limited-to-8-cycles group (OS: HR 0.86, p = 0.007). Neither the durvalumab nor pembrolizumab groups statistically improved the OS compared to the gemcitabine-maintenance group. In contrast, the durvalumab and pembrolizumab groups significantly improved OS compared to the gemcitabine-limited-to-8-cycles group. Conclusions: Based on this mimic head-to-head analysis, we are convinced that durvalumab and pembrolizumab benefit patients with biliary tract cancer. However, despite the statistically significant differences, the moderate progress made in OS and PFS might still be considered inadequate. It is crucial for clinicians to identify the precise subgroup population that could benefit most from immunotherapy and develop more strategies for those who might not respond well to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy., Methods: Records were identified through a formal search of PubMed and Web of Science. The TOPAZ-1 and KEYNOTE-966 trials were definitively included. Patient-level overall survival (OS) and progression-free survival (PFS) data were reconstructed and analyzed using a one-stage approach., Results: The immunotherapy plus GP chemotherapy group showed superiority over the GP chemotherapy group (OS: HR 0.83, p < 0.001; PFS: HR 0.88, p = 0.009). The survival outcomes were similar between the durvalumab and pembrolizumab groups (OS: HR 1.02, p = 0.83; PFS: HR 0.95, p = 0.53). In the subgroup analysis, the gemcitabine-maintenance group significantly prolonged the OS compared to the gemcitabine-limited-to-8-cycles group (OS: HR 0.86, p = 0.007). Neither the durvalumab nor pembrolizumab groups statistically improved the OS compared to the gemcitabine-maintenance group. In contrast, the durvalumab and pembrolizumab groups significantly improved OS compared to the gemcitabine-limited-to-8-cycles group., Conclusions: Based on this mimic head-to-head analysis, we are convinced that durvalumab and pembrolizumab benefit patients with biliary tract cancer. However, despite the statistically significant differences, the moderate progress made in OS and PFS might still be considered inadequate. It is crucial for clinicians to identify the precise subgroup population that could benefit most from immunotherapy and develop more strategies for those who might not respond well to immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Kuang, Lin and Fu.)

Background: The poor prognosis of anaplastic thyroid cancer (ATC) patients is associated with limited effective therapeutic strategies. Multiple antiangiogenesis tyrosine kinase inhibitors (TKIs) have been applied in later-line treatment of ATC; however, the results reported in clinical trials were controversial. In this study, we reconstructed the patient-level data to pooled-analyze the survival data, responses, and adverse events., Methods: Online databases (PubMed, Web of Science, Embase, and Cochrane CENTRAL) were searched on September 03, 2023. R software combined with the "metaSurvival" and "meta" packages were used to reconstruct the survival curves and summarize the response rates. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were survival rate, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events., Results: Six prospective clinical trials involving 140 ATC patients were enrolled. Four types of TKIs (imatinib, pazopanib, sorafenib, and lenvatinib) were included. When advanced ATC patients were treated with the TKIs, the median OS was 4.8 months and the median PFS was 2.6 months. The pooled ORR and DCR were 9% and 53%. Hypertension, decreased appetite, rash, and lymphopenia were the most common grade ≥ 3 treatment-related adverse events., Conclusion: Mono-anitangiogenesis TKI therapy showed limited improvements in treating advanced ATC patients. Combining antiangiogenesis TKI therapy with chemotherapy, radiotherapy, or immunotherapy could be the direction of future studies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: For patients with anaplastic thyroid cancer (ATC) without mutational driver genes, chemotherapy is suggested to be the first-line treatment option. However, the benefits of chemotherapy in treating ATC are limited. In this analysis, we collected the prospective data reported since 2010 to analyze the emerging chemotherapy-based treatments in ATC comprehensively., Methods: For this updated analysis, we searched PubMed (MEDLINE), Web of Science, Embase, and Cochrane CENTRAL databases from 1 January 2010 to 7 February 2024 for prospective clinical studies that contained chemotherapy-based treatments. This analysis was done to pool overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), disease control rates (DCRs), and grade 3 or worse treatment-related adverse events (TRAEs)., Results: Six prospective clinical trials with 232 patients were included. Chemotherapy was commonly combined with targeted therapy or radiotherapy. The pooled median OS was 6.0 months (95% CI 4.1-9.7), and the median PFS was 3.2 months (95% CI 1.9-6.0) in patients with ATC who received chemotherapy-based strategies. The integrated ORR and DCR were 21% (95% CI 15%-27%) and 64% (95% CI 55%-72%), respectively. Regarding the grade 3 or worse TRAE, the pooled incidence was 68% (95% CI 47%-86%)., Conclusion: Although the emerging chemotherapy-based treatments showed antitumor activity in patients with ATC, these strategies failed to prolong the survival time substantially. More practical, safe, and novel therapeutic regimens for patients with ATC warrant further investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Lin, Kuang and Cao.)

Background: Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients., Methods: We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR)., Results: 12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%)., Conclusion: In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kuang, Zhang, Lin, Fu, Cao and Wang.)