Background: Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, the causal association between gut microbiota and cancer remains to be determined. Methods: We first identified two sets of gut microbiota based on phylum, class, order, family, and genus level information, and cancer data were obtained from the IEU Open GWAS project. We then performed two-sample Mendelian randomisation (MR) to determine whether the gut microbiota is causally associated with eight cancer types. Furthermore, we performed a bi-directional MR analysis to examine the direction of the causal relations. Results: We identified 11 causal relationships between genetic liability in the gut microbiome and cancer, including those involving the genus Bifidobacterium. We found 17 strong associations between genetic liability in the gut microbiome and cancer. Moreover, we found 24 associations between genetic liability in the gut microbiome and cancer using multiple datasets. Conclusions: Our MR analysis revealed that the gut microbiota was causally associated with cancers and may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer.

Background: Antibody–drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance.Methods: In a systematic review and meta‐analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random‐effects model with logit transformation and evaluated the heterogeneity between studies using I² statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all‐grade and grade ≥3 treatment‐related adverse events and differences between different drugs, molecular structures, and cancer types.Results: In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment‐related adverse events was 91.2% (95% CI, 90.7%–91.7%; I² = 95.9%) for all‐grade adverse events and 46.1% (95% CI, 45.2%–47.0%; I² = 96.3%) for grade ≥3 adverse events. The most common all‐grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%–57.3%), nausea (44.1%; 95% CI, 43.2%–44.9%), neutropenia (43.7%; 95% CI, 42.6%–44.9%), blurred vision (40.5%; 95% CI, 37.4%–43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%–41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%–32.3%), hypoesthesia (23.3%; 95% CI, 10.6%–35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%–23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%–23.1%), and lymphopenia (21.0%; 95% CI, 18.2%–23.7%).Conclusions: Different ADCs appear to affect various treatment‐related adverse events and provide comprehensive data on treatment‐related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.Lay summary: Unique anticancer drugs called antibody–drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment‐related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

Introduction: The ASTRUM-005 trial (NCT04063163) revealed that combination serplulimab plus chemotherapy (etoposide and carboplatin [EC]) treatment was associated with survival advantages relative to chemotherapy alone in patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC). As these immuno-chemotherapeutic regimens are extremely expensive, however, it is critical that the relative cost-effectiveness of combination serplulimab and chemotherapy treatment as a first-line treatment for ES-SCLC patients be examined in detail.Methods: The cost-effectiveness of combined serplulimab plus chemotherapeutic treatment was examined using a comprehensive Markov model with a 10-year boundary, enabling the calculation of overall cost, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model instability was interrogated through one-way and probabilistic sensitivity analyses.Results: Serplulimab plus chemotherapy or chemotherapy alone respectively yielded 1.217 QALYs (2.243 LYs) and 0.885 QALYs (1.661 LYs) with corresponding total costs of $11,202 and $7,194, with an ICER of $12,077 per QALY ($6,883 per LY). This model was most strongly influenced by the utility of progression-free survival. Probabilistic sensitivity analysis showed that serplulimab plus chemotherapy had a 91.6% probability of being cost-effective at a willingness-to-pay (WTP) of $37,653 per QALY (3 × capita gross domestic product of China in 2021). In subgroup analyses, this combination treatment regimen was found to be most cost-effective in patients who were former smokers, had an ECOG performance status of 0, and were diagnosed with brain metastases.Conclusion: From a payer perspective in China, combination serplulimab plus chemotherapy treatment represents a cost-effective first-line intervention for ES-SCLC patients.