Incidence of thyroid dysfunction caused by immune checkpoint inhibitors combined with chemotherapy: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy as a first-line treatment for triple-negative breast cancer (TNBC) has been associated with many adverse reactions. Thyroid dysfunction, the most common adverse reaction of the endocrine system, has also attracted significant attention. This study aimed to analyse the effect of ICIs combined with chemotherapy on thyroid function in patients with TNBC. METHODS: As of November 4, 2023, we searched the PubMed, Web of Science, and Cochrane Library databases for clinical trials of ICIs combined with chemotherapy for the treatment of TNBC. The incidence of hypothyroidism and hyperthyroidism was calculated using a random-effects model. RESULTS: In the final analysis, 3,226 patients from 19 studies were included. The total incidence of all-grade hypothyroidism induced by the combination of ICIs and chemotherapy in treating TNBC (12% (95% confidence intervals(CI): 0.10-0.15)) was higher than that of hyperthyroidism (5% (95% CI: 0.04-0.06)). Pembrolizumab combined with chemotherapy caused the highest incidence of all grades of hypothyroidism for 13% (95% CI: 0.05-0.06). Durvalumab combined with chemotherapy caused the highest incidence of all grades of hyperthyroidism, at 7% (95% CI: 0.03-0.11). ICIs combined with chemotherapy caused a higher incidence of all grades of hypothyroidism in advanced TNBC (15% (95% CI: 0.13-0.17)) than in early stage TNBC (10% (95% CI: 0.07-0.13)). CONCLUSION: In TNBC, the incidence of hypothyroidism caused by the combination of ICIs and chemotherapy was significantly higher than that caused by hyperthyroidism. Pembrolizumab combined with chemotherapy resulted in the highest incidence of hypothyroidism. The incidence of hypothyroidism in patients with advanced TNBC was significantly higher than that in patients with early stage TNBC. In addition, ICIs combined with chemotherapy resulted in 16 out of 3,226 patients experiencing grade ≥ 3 thyroid dysfunction. Although the incidence of severe thyroid dysfunction is low, it requires attention. PROSPERO: CRD42023477933.

Long-term survival after neoadjuvant therapy for triple-negative breast cancer under different treatment regimens: a systematic review and network meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC. METHODS: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS. RESULTS: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%). CONCLUSIONS: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR.

Efficacy and safety of first-line treatment for metastatic triple-negative breast cancer: A network meta-analysis.

Background: Metastatic triple-negative breast cancer (mTNBC) is an aggressive histological subtype with poor prognosis. Several first-line treatments are currently available for mTNBC. This study conducted a network meta-analysis to compare these first-line regimens and to determine the regimen with the best efficacy. Methods: A systematic search of PubMed, EMBASE, the Cochrane Central Register of Controlled Bases, and minutes of major conferences was performed. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analyzed via network meta-analysis using the R software (R Core Team, Vienna, Austria). The efficacy of the treatment regimens was compared using hazard ratios and 95% confidence intervals. Results: A total of 29 randomized controlled trials involving 4607 patients were analyzed. The ranking was based on the surface under the cumulative ranking curve. Network meta-analysis results showed that cisplatin combined with nab-paclitaxel or paclitaxel was superior to docetaxel plus capecitabine in terms of PFS and ORR. For programmed death-ligand 1 (PD-L1) and breast cancer susceptibility gene (BRCA) mutation-positive tumors, atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib was superior to docetaxel plus capecitabine. No significant difference was observed among the treatments in OS. Neutropenia, diarrhea, and fatigue were common serious adverse events. Conclusion: Cisplatin combined with nab-paclitaxel or paclitaxel is the preferred first-line treatment for mTNBC. For PD-L1 and BRCA mutation-positive tumors, atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option. Neutropenia, diarrhea, and fatigue are frequently occurring serious adverse events.

Incidence of antibody-drug conjugate-related fatigue in patients with breast cancer: A systematic review and meta-analysis.

BACKGROUND: Numerous studies have reported the efficacy of antibody-drug conjugates (ADCs) for treating breast cancer. However, during cytotoxic drug treatment, long-term disabling fatigue is common. Moreover, studies in the relevant literature have indicated that fatigue can significantly increase the incidence of depression and sleep disorders. Therefore, this meta-analysis aims to evaluate the incidence of fatigue in breast cancer survivors treated with ADCs. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for articles and conference abstracts published before March 16, 2023. Further, two authors independently extracted data from the included studies. The primary outcome of this study was the incidence of all-grade fatigue caused by the use of ADCs in patients with breast cancer. Finally, a random-effects model was used to calculate the incidence and 95% confidence intervals (CIs) of the outcome. RESULTS: Overall, 7963 patients from 31 studies were included in this meta-analysis to assess the incidence of fatigue caused by the use of approved and marketed ADCs in patients with breast cancer. Notably, the incidence of all-grade fatigue during ADC monotherapy was 39.84% (95% CI, 35.09%-44.69%). In subgroup analyses, among ADCs, the incidence of trastuzumab deruxtecan-induced fatigue was the highest, with an all-grade fatigue incidence of 47.05% (95% CI, 42.38%-51.75%). Meanwhile, the incidence of trastuzumab emtansine (T-DM1)-induced all-grade fatigue was 35.17% (95% CI, 28.87%-41.74%), which was the lowest among ADCs. Further, the incidence of all-grade fatigue due to sacituzumab govitecan was 42.82% (95% CI, 34.54%-51.32%), which was higher than that due to T-DM1. Moreover, the incidence of fatigue was higher with T-DM1 combination therapy than with monotherapy. CONCLUSIONS: Clinicians have highlighted the high incidence of ADC-related fatigue and its negative impact on patients' physical and mental health, making fatigue an important research variable. The results of this study will further contribute to a comprehensive understanding of ADCs, which have some clinical importance and are of great benefit to patients with breast cancer.

The correlation between systemic inflammatory markers and efficiency for advanced gastric cancer patients treated with ICIs combined with chemotherapy.

Currently lacking research to explore the correlation between inflammatory markers and the efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in the treatment of advanced gastric cancer. This study is a retrospective study and included patients with advanced gastric cancer who receiving ICIs combined with chemotherapy from January 2020 to December 2022. We analysed the relationship between systemic inflammatory markers and the efficacy of ICIs combined chemotherapy and constructed a clinical prediction model. A nomogram was constructed based on the results of the bidirectional stepwise regression model. A total of 197 patients were enrolled in the training group, with a median follow-up period of time 26 months. Kaplan Meier analysis showed that the median OS of patients with low systemic immune-inflammatory index (SII) and low platelet to lymphocyte ratio (PLR) was superior to those with high SII and PLR. Univariate and multivariate Cox regression analysis showed that SII, NLR, PLR, and N stage as independent prognostic factors for OS. Adding SII to the conventional model improved the predictive ability of the 12-month OS. A total of 95 patients were included in the validation group, and external validation of the SII-based nomogram showed favourable predictive performance. Baseline SII, PLR, and N stage may serve as independent predictive factors for survival outcomes in advanced gastric cancer patients undergoing ICIs combined with chemotherapy. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.

Screening Single Nucleotide Polymorphisms Predicting the Efficacy of Electroacupuncture for Fatigue Treatment in Patients with Breast Cancer Following Adjuvant Chemotherapy.

Chemotherapy-induced fatigue reduces not only the quality of life of patients but also effect their recurrence-free survival rate. Although electroacupuncture can relieve fatigue, it has limited affect on some patients. Therefore, appropriate biomarkers are needed to help screen patients who can benefit from electroacupuncture treatment of fatigue. We conducted this study to explore the predictive ability of SNPs on the efficacy of electroacupuncture in the treatment of fatigue in patients with breast cancer after adjuvant chemotherapy. Our study included breast cancer patients with fatigue after receiving paclitaxel and/or anthracycline based adjuvant chemotherapy. The patients were divided into the electroacupuncture group and the control group. The electroacupuncture treatment group received adjuvant chemotherapy and electroacupuncture treatment, while the control group only received adjuvant chemotherapy, and then compared the fatigue relief degree of two groups. In addition, we used NCBI dbSNP and PharmGKB databases to select fatigue related genes and their SNPs. We collected peripheral blood from the included patients for SNPs typing, and recorded the efficacy of electroacupuncture to analyzed the correlation between different SNPs and therapeutic efficacy. The side effects of electroacupuncture treatment were also recorded. 76 patients in the electroacupuncture group and 48 patients in the control group were enrolled. In the electroacupuncture group, 63 patients (82.9%) experienced moderate to severe fatigue (BFI score > 3). After electroacupuncture treatment, the number of patients with a BFI score of > 3 was 46 (60.5%). Therefore, the fatigue symptoms of 26.9% patients were significantly improved (P < 0.05). In the control group, which did not receive electroacupuncture treatment, 40 of 48 patients had a BFI score of > 3. Following the same observation time used in the electroacupuncture group, 36 patients had a BFI score of > 3 points. Thus, fatigue was not significantly relieved in the control group (83.3% vs. 75.0%, P > 0.05). We included 56 patients in our analysis of the correlation between SNPs and electroacupuncture treatment effects. We divided the patients into an effective group and ineffective group according to therapeutic effects. Our results indicated that the effective rate of electroacupuncture treatment with IL1A rs3783550 AC and CC genotypes was higher than that with other genotypes (AC: 84.6%, CC: 81.8%, AA: 33.0%, P < 0.05). Similarly, the effective rate of electroacupuncture treatment with HTR1A rs6295 GG and CC genotypes was higher than that with other genotypes (GG: 63.0%, CC: 55.6%, GC: 18.2%, P < 0.05). However, no other genotypes were related to the effect of electroacupuncture treatment on fatigue. Our result showed that electroacupuncture has therapeutic effect on fatigue after adjuvant chemotherapy for breast cancer and the side effects are tolerable. In addition, IL1A rs3763550 and HTR1A rss6295 can predict the therapeutic effect of electroacupuncture on fatigue after adjuvant chemotherapy in breast cancer, which helps to better screen patients who can benefit from electroacupuncture treatment.

Incidence rate of osteonecrosis of jaw after cancer treated with bisphosphonates and denosumab: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to assess the overall incidence of osteonecrosis of the jaw (ONJ) caused by bisphosphonates and denosumab when used for controlling bone cancer metastasis or as adjuvant therapy. SUBJECTS AND METHODS: A systematic search of the PubMed, Embase, and Cochrane Library databases and major meetings' proceedings as of July 30, 2022, identified randomized controlled trials (RCTs) and observational trials that evaluated ONJ caused by denosumab or bisphosphonates. The total incidence and risk ratio (RR) for ONJ were calculated using a random-effects model. RESULTS: A total of 42 003 patients with various solid tumors reported in 23 RCTs were included. The overall ONJ incidence in cancer patients receiving denosumab or bisphosphonates was 2.08% (95% CI 1.37-2.91; p < .01; I2  = 94.99%). Patients receiving denosumab had a higher ONJ incidence than those receiving bisphosphonates (RR 1.64, 95% CI 1.10-2.44; p < .05; I2  = 65.4%). Subgroup analyses showed that prostate cancer patients receiving denosumab and receiving zoledronic acid had the highest ONJ incidences, 5.0% and 3.0%, respectively. The incidence of ONJ induced by different doses was also different. CONCLUSIONS: The incidence of ONJ caused by denosumab and bisphosphonates is low, the dose of the drug and the type of cancer have certain influence on ONJ. Therefore, clinicians should use the drug reasonably to improve the quality of life of patients.

Third-line Treatment for Metastatic Triple-negative Breast Cancer: A Systematic Review and Network Meta-analysis.

OBJECTIVE: Metastatic triple-negative breast cancer (mTNBC) is an invasive histologic subtype with a poor prognosis and rapid progression. Currently, there is no standard therapy for the third-line treatment of mTNBC. In this study, we conducted a network meta-analysis to compare regimens and determine treatment outcomes. METHODS: We performed a systematic search of PubMed, EMBASE, the Cochrane Central Register of Controlled Bases, and the minutes of major conferences. Progression-free survival, overall survival, and objective response rate were analyzed through network meta-analysis using the R software (R Core Team). The efficacy of the treatment regimens was compared using hazard ratios, odds ratios, and 95% CIs. RESULTS: We evaluated 15 randomized controlled trials involving 6,010 patients. Compared with the physician's choice treatment, sacituzumab govitecan showed significant advantages in progression-free survival and overall survival, with hazard ratio values of 0.41 (95% CI: 0.32-0.52) and 0.48 (95% CI, 0.39-0.60). In terms of objective response rate, sacituzumab govitecan is the best-performing therapy (odds ratio: 10.82; 95% CI: 5.58-20.97). Adverse events among grades 3 to 5 adverse reactions, the incidence of neutropenia and leukopenia in each regimen was higher, whereas the incidence of fever, headache, hypertension, and rash was lower. CONCLUSION: Compared with the treatment of the physician's choice, sacituzumab govitecan appears more efficacious and is the preferred third-line treatment for mTNBC.

Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis.

Background: The wide use of antibody-drug conjugates (ADCs) is transforming the cancer-treatment landscape. Understanding the treatment-related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta-analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods: We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all-grade and grade ≥ 3 treatment-related AEs were the primary outcomes of the analysis. Results: A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any-grade treatment-related AEs was 100.0% (95% confidence interval [CI]: 99.9%-100.0%; I 2 = 89%) and the incidence of grade ≥ 3 treatment-related AEs was 6.2% (95% CI: 3.0%-12.4%; I² = 99%). Conclusions: This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any-grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.

Elevated expression of TUBA1C in breast cancer predicts poor prognosis.

α1C-tubulin (TUBA1C) is a member of the α-tubulin family and has served as a potential biomarker in a variety of cancers in many studies. In this study, the gene expression profile of TUBA1C in The Cancer Genome Atlas (TCGA) was extracted for analysis, and the prognostic value of TUBA1C in breast cancer was comprehensively evaluated. The Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression analysis were performed to confirm the correlations between TUBA1C expression and the clinical characteristics of breast cancer patients. The effect of TUBA1C expression on the survival of breast cancer patients was assessed by Kaplan-Meier curve, Cox regression analysis, and the Kaplan-Meier plotter (an online database). The TCGA data set was used for the Gene Set Enrichment Analysis (GSEA). The results confirmed that high TUBA1C expression in breast cancer was closely correlated with survival time, survival status, and tumor size. In addition, elevated TUBA1C expression can predict poor overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Univariate and multivariate analyses (Cox regression analyses) confirmed that TUBA1C was an independent prognostic factor for the OS of breast cancer patients. The GSEA identified that the high TUBA1C expression phenotype was differentially enriched in cell cycle, basal transcription factor, P53 signaling pathway, pathways in cancer, TOLL-like receptor signaling pathway, and NOD-like receptor signaling pathway. In summary, high messenger RNA (mRNA) expression of TUBA1C is an independent risk factor for poor prognosis of breast cancer.

Meta-analysis of quality of life in patients with cancer treated with antibody-drug conjugates in randomized controlled trials.

Purpose: To evaluate the patient-reported outcomes of patients treated with commercially approved antibody-drug conjugates (ADC) reported in randomized controlled trials (RCT) published up to September 2023. Methods: A meta-analysis of 6430 patients from 12 randomized controlled trials was conducted. Results: No significant change was observed between the groups from baseline to end of treatment and end of follow-up, with a standardized mean difference of -0.08 (95% CI: -0.27-0.12) and 0.01 (95% CI: -0.11-0.12), respectively. Treatment with ADCs delayed the deterioration of patients' clinical condition compared with treatment with non-ADCs, with a hazard ratio of 0.78 (95% CI: 0.67-0.92). Conclusion: ADCs have a good correlation with delay of clinical deterioration in patients with cancer.

Cytochrome b561 regulates iron metabolism by activating the Akt/mTOR pathway to promote Breast Cancer Cells proliferation.

Breast cancer (BC) is the leading cause of cancer-related mortality in women, necessitating the development of novel therapeutic targets. While cytochrome b561 (CYB561) expression is associated with poor prognosis in BC, the precise role of CYB561 in BC and its potential mechanisms remain unclear. In the present study, we found that CYB561 plays an essential role in BC growth. CYB561 expression was up-regulated in surgically resected cancerous tissues and in six BC cell lines. Lentivirus-mediated CYB561 knockdown in BC cells significantly reduced their proliferation, migration, and invasiveness. CYB561 participates in the regulation of iron metabolism in BC. CYB561 knockdown reduced total iron content, increased ferrous iron content, and down-regulated the expression of proteins associated with iron metabolism (transferrin receptor 1, divalent metal transporter 1, and ferritin heavy chain 1). Conversely, up-regulation of CYB561 through co-incubation with exogenous iron (ferric ammonium citrate) produced contrary outcomes. Additionally, CYB561 activated the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway in BC cells. Down-regulation of CYB561 expression inhibited the Akt/mTOR signaling pathway activity. The application of an mTOR agonist (MHY1485) rescued this negative effect, as well as the inhibitory effect of CYB561 knockdown on cell proliferation. Importantly, the dual mTOR inhibitor MLN0128 (50 nM, 48 h) down-regulated CYB561 expression and the iron metabolism-related proteins transferrin receptor, divalent metal transporter 1, and ferritin heavy chain 1, whereas the mTOR agonist MHY1485 rescued the down-regulation of CYB561 knockdown on iron metabolism-related proteins. We conclude that CYB561 promotes the proliferation of BC cells by regulating iron metabolism through the activation of the Akt/mTOR signaling pathway.

Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy.

BACKGROUND: Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial. MATERIALS AND METHODS: We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival. RESULTS: A total of 479 patients were enrolled, with a median follow-up period of time was 36 months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25-15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65-2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46-5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35-0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS. CONCLUSION: To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS.

Second-line Endocrine Therapy of Hormone Receptor-positive/HER2- negative Advanced Breast Cancer: A Systematic Review and Network Meta-analysis.

BACKGROUND: The optimal second-line therapy for hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer is yet to be established. Therefore, we conducted a network meta-analysis (NMA) of marketed drugs to compare their efficacy. METHODS: We searched the literature in PubMed, Embase, Web of Science databases, and the main international conferences in the past 5 years to find phase III clinical trials on drugs available in the market. Network meta-analysis of progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) was performed using R software. The efficiency of treatment options was compared using hazard ratios and 95% credibility intervals. RESULTS: Overall, 12 studies with 6120 patients were included in the analysis. In an indirect comparison of the five regimens, cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) plus 500 mg fulvestrant (Ful500) gave the best PFS results; palbociclib ranked first with a surface under the cumulative ranking (SUCRA) of 94.99%, followed by mammalian target of rapamycin inhibitor (mTORi) plus everolimus (SUCRA=73.07%), phosphoinositide 3-kinase inhibitor (PI3Ki) plus Ful500 (SUCRA=66.73%), Ful500 alone (SUCRA=44.55%), and histone deacetylase inhibitor (HDACi) plus exemestane (SUCRA= 43.49%). However, no significant difference was found in the PFS rates of CDK4/6i, mTORi, and PI3Ki. For OS, CDK4/6i plus Ful500 ranked first; the SUCRA of ribociclib, abemaciclib, and palbociclib were 86.20%, 83.98%, and 78.52%, respectively. Alpelisib plus Ful500 (SUCRA=66.91%) ranked second but was not statistically different from CDK4/6i. The mTORi plus everolimus group had the best ORR (SUCRA=88.73%). In terms of safety, 81.56% of patients in the tucidinostat plus exemestane regimen developed neutropenia, suggesting strong hematological toxicity; 13.40% of patients developed grade 3-4 diarrhea after using abemaciclib plus Ful500. CONCLUSION: For second-line endocrine therapy in HR+/HER2- advanced/metastatic breast cancer, CDK4/6i is a better choice than mTORi, PI3Ki, HDACi, and Ful; it shows good PFS and OS outcomes and a low probability for serious adverse events.>.

Efficacy of anti-HER2 drugs in the treatment of patients with HER2-mutated cancers: a systematic review and meta-analysis.

Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.

The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis.

Background: The use of antibody-drug conjugates for the treatment of advanced-stage human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer (BC) has shown prominent curative effects, which has led to increased academic interest. However, the role of HER2-low expression in the prognosis of BC remains controversial. Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane library databases and several oncology conferences until 20 September 2022. We used fixed- and random-effects models to calculate odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and pathological complete response (pCR) rates. Results: Overall, 26 studies encompassing 677,248 patients were included in the meta-analysis. Patients with HER2-low BC showed significantly better OS than those with HER2-zero BC in the overall population (HR = 0.90; 95% CI: 0.85-0.97) and hormone receptor-positive population (HR = 0.98; 95% CI: 0.96-0.99), whereas no significant difference was observed in the OS of the hormone receptor-negative population (p > 0.05). In addition, there was no significant difference in the DFS of the overall and hormone receptor-negative population (p > 0.05), but better DFS than those with HER2-zero BC in the hormone receptor-negative population (HR = 0.96; 95% CI: 0.94-0.99). There was also no significant difference in the PFS of the overall population, hormone receptor-positive, and hormone receptor-negative population (p > 0.05). Patients with HER2-low BC had a lower pCR rate after neoadjuvant treatment than those with HER2-zero BC. Conclusions: Compared to patients with HER2-zero BC, those with HER2-low BC had better OS in the overall population and hormone receptor-positive population, DFS in hormone receptor-positive population and lower pCR in the overall population. The biological differences between HER2-low and HER2-zero BCs, particularly in hormone receptor-positive patients, and the relationship between HER2-low expression status and prognosis need to be explored further.

Treatment options for patients with human epidermal growth factor 2-positive breast cancer brain metastases: A systematic review and meta-analysis.

Introduction: Many systemic treatment options are available for patients with human epidermal growth factor 2 (HER2)-positive breast cancer brain metastases. However, it is unclear which pharmacological treatment option is the most beneficial. Methods: We searched databases, such as PubMed, Embase, and Cochrane Library, and conference abstracts according to keywords. We extracted progression-free survival (PFS), overall survival (OS) data, and overall response rate (ORR) from randomized controlled trials and single-arm studies of HER2-positive breast cancer brain metastasis treatment for meta-analysis and analyzed different drug-related adverse events (AEs). Results: Three randomized controlled trials and seven single-arm clinical studies with 731 patients with HER2-positive brain metastases from breast cancer involving at least seven drugs were included. In randomized controlled trials, our results showed that trastuzumab deruxtecan significantly improved PFS and OS in patients and was superior to other drug regimens. In the single-arm study, the ORR was more pronounced for the trastuzumab deruxtecan and pyrotinib plus capecitabine regimens (ORR, 73.33%; 95% confidence intervals [CI], 44.90%-92.21%; ORR, 74.58%; 95% CI, 61.56%-85.02%, respectively). We found that the main AEs of antibody-drug conjugate (ADC) were nausea and fatigue, while the main AE of small-molecule tyrosine kinase inhibitor (TKI) drugs and large monoclonal antibodies was diarrhea. Conclusions: Trastuzumab deruxtecan was shown to be the most significant in improving survival in patients with HER2-positive breast cancer brain metastases in network meta-analysis, and in single-arm study, patients with HER2-positive breast cancer brain metastases treated with trastuzumab deruxtecan and pyrotinib plus capecitabine regimen had the highest ORR. The main AEs associated with ADC, large monoclonal antibodies, and TKI drugs were nausea, fatigue, and diarrhea, respectively.

Impact of platinum-based chemotherapy on the prognosis of early triple-negative breast cancer: a systematic review and meta-analysis.

Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of platinum-based neoadjuvant and adjuvant chemotherapy is still controversial. Our meta-analysis aimed at analyzing survival with platinum-based neoadjuvant and adjuvant chemotherapy in patients with TNBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases, and several major conferences up to January 2021. Fixed and random models were used for our meta-analysis. Disease-free survival (DFS), overall survival (OS), and side effects data were extracted from the included literature in addition to the corresponding pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). A total of nine studies involving 3247 patients were included. The pooled analysis suggested that compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy could further improve DFS (HR = 0.56, 95% CI 0.45-0.67, p < 0.01) and OS (HR = 0.54, 95% CI 0.38-0.70, p < 0.01) in patients with TNBC. The subgroup analysis showed that platinum-based chemotherapy could further improve DFS (HR = 0.59, 95% CI 0.43-0.74, p < 0.01) and OS (HR = 0.61, 95% CI 0.40-0.83, p < 0.01) in neoadjuvant chemotherapy and DFS (HR = 0.53, 95% CI 0.37-0.69, p < 0.01) and OS (HR = 0.46, 95% CI 0.23-0.69, p < 0.01) in adjuvant chemotherapy compared with anthracycline- and/or paclitaxel-based chemotherapy in patients with TNBC. In addition, compared with anthracycline-based chemotherapy, platinum-based chemotherapy without anthracycline chemotherapy could further improve DFS (HR = 0.53, 95% CI 0.37-0.70, p < 0.01) and OS (HR = 0.46, 95%CI 0.19-0.72, p < 0.01) in patients with TNBC. Compared with anthracycline- and/or paclitaxel-based chemotherapy, all-grade diarrhea, fatigue, and grade ≥ 3 anemia were higher in platinum-based chemotherapy. In contrast, all-grade anemia, leukopenia, neutropenia, peripheral neuropathy, myalgia/arthralgia, cardiac toxicity were lower in platinum-based chemotherapy; grade ≥ 3 leukopenia, neutropenia and myalgia/arthralgia were also lower. Compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy was more associated with improved DFS and OS in TNBC patients. The benefit of survival is consistent with platinum-based neoadjuvant and adjuvant chemotherapy. The side effects of platinum-based chemotherapy are tolerable.

Watson for oncology decision system for treatment consistency study in breast cancer.

The Watson for Oncology (WFO) decision system has been rolled out in many cancers. However, the consistency of treatment for breast cancer is still unclear in relatively economically disadvantaged areas. Patients with postoperative adjuvant stage (January 2017 to December 2017) and advanced-stage breast cancer (January 2014 to December 2018) in northwest of China were included in this study. Patient information was imported to make treatment decisions using Watson version 19.20 analysis and subsequently compared with clinician decisions and analyzed for influencing factors. A total of 263 patients with postoperative adjuvant breast cancer and 200 with advanced breast cancer were included in this study. The overall treatment modality for WFO was in 80.2% and 50.5% agreement with clinicians in the adjuvant and advanced-stage population, respectively. In adjuvant treatment after breast cancer surgery, menopausal status (odds ratio (OR) = 2.89, P = 0.012, 95% CI, 1.260-6.630), histological grade (OR = 0.22, P = 0.019, 95% CI, 0.061-0.781) and tumor stage (OR = 0.22, P = 0.042, 95% CI, 0.050-0.943) were independent factors affecting the concordance between the two stages. In the first-line treatment of advanced breast cancer, hormone receptor status was a factor influencing the consistency of treatment (χ2 = 14.728, P < 0.001). There was good agreement between the WFOs and clinicians' treatment decisions in postoperative adjuvant breast cancer, but poor agreement was observed in patients with advanced breast cancer.

Comparative efficacy and safety of first-line neoadjuvant treatments in triple-negative breast cancer: systematic review and network meta-analysis.

Neoadjuvant treatment options for triple-negative breast cancer (TNBC) are abundant, but the efficacy of different combinations of treatment options remains unclear. Our network meta-analysis aimed to evaluate the effectiveness and safety of various neoadjuvant treatment options in patients with TNBC. Literature reports published before March 31, 2022, were retrieved from the PubMed, Embase, Cochrane Library, main oncology conference of the European Society of Medical Oncology, American Society of Clinical Oncology, and San Antonio Breast Cancer Symposium databases. Pairwise and Bayesian network meta-analyses were performed to compare direct and indirect evidence, respectively. The primary outcome was pathological complete response (pCR). Comparison of efficiency between different treatment regimens was made by HRs and 95% confidence intervals (CIs). Overall, 26 studies, including 9714 TNBC patients, were assessed in this network meta-analysis. Results indicated that the pCR of immune checkpoint inhibitors plus platinum-containing regimens is better than other joint regimens. PCR rate of neoadjuvant chemotherapy regimens containing bevacizumab, platinum, poly(ADP-ribose) polymerase inhibitors, and immune checkpoint inhibitors was higher than those of standard chemotherapy agents. By performing a conjoint analysis of the pCR rate and safety endpoints, we found that immune checkpoint inhibitors plus platinum-containing regimens were well balanced in terms of efficacy and toxicity. Considering the efficacy and acceptable adverse events, neoadjuvant chemotherapy based on immune checkpoint inhibitors plus platinum may be considered as an option for patients with TNBC.