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Journal of Cancer Research and Clinical... Jan 2024The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive... (Meta-Analysis)
Meta-Analysis
PURPOSE
The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive evaluation to inform clinical decision-making. We conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions.
METHODS
We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts from inception to June 1, 2023. NMA was performed to calculate and analyze progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events of grade 3 or higher (≥ 3 AEs).
RESULTS
Out of the 10,313 manuscripts retrieved, we included 28 RCTs involving 11,680 patients. Regarding PFS and ORR, the combination of trastuzumab with tyrosine kinase inhibitors (TKIs) was more favorable than dual-targeted therapy. If only using trastuzumab, combination chemotherapy is superior to monochemotherapy in terms of PFS. It is important to note that the addition of anthracycline did not result in improved PFS. For patients with hormone receptor-positive HER2-positive diseases, dual-targeted combined with endocrine therapy showed better benefit in terms of PFS compared to dual-targeted alone, but it did not reach statistical significance. The comprehensive analysis of PFS and ≥ 3 AEs indicates that monochemotherapy combined with dual-targeted therapy still has the optimal balance between efficacy and safety.
CONCLUSION
Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.
Topics: Humans; Female; Network Meta-Analysis; Randomized Controlled Trials as Topic; Breast Neoplasms; Trastuzumab; Receptor, ErbB-2; Docetaxel; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38244085
DOI: 10.1007/s00432-023-05530-3 -
Breast Cancer Research and Treatment Apr 2024The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However,... (Meta-Analysis)
Meta-Analysis Review
The association between HER2-low status and survival in patients with metastatic breast cancer treated with Cyclin-dependent kinases 4 and 6 inhibitors: a systematic review and meta-analysis.
PURPOSE
The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However, biomarkers predicting long-term benefit and early progression are yet to be defined. Several studies suggested the possibility of diminished efficacy in patients with HER2-low disease. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between low-level HER2 expression and efficacy outcomes (PFS, OS, ORR) with CDK 4/6 inhibitors.
METHODS
The Pubmed, Web of Science, and Scopus databases were used to systematically filter the published studies from inception to 08 August 2023 for this systemic review. Studies including MBC patients treated with CDK 4/6 inhibitors and reported survival outcomes according to HER2 expression were included. We performed the meta-analyses with the generic inverse-variance method with a fixed-effects model and used HRs with 95% two-sided CIs as the principal summary measure.
RESULTS
Nine studies encompassing 2705 patients were included in the analyses. In the pooled analysis of nine studies, the risk of progression and/or death was higher in patients with HER2-low tumors compared to HER2-zero (HR: 1.22, 95% CI 1.10-1.35, p < 0.001). In the pooled analysis of five studies, although the median follow-up was short, the risk of death was higher in the HER2-low group compared to the HER2-zero group (HR: 1.22, 95% CI 1.04-1.44, p = 0.010).
CONCLUSION
The available evidence demonstrates a significantly higher risk of progression or death with CDK 4/6 inhibitors in HER2-low tumors. Further research is needed to improve outcomes in patients with HR+-HER2-low tumors.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Protein Kinase Inhibitors; Cyclin-Dependent Kinase 4; Cyclins; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38240935
DOI: 10.1007/s10549-023-07226-1 -
Pharmacological Research Feb 2024To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors.
METHODS
We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest.
RESULTS
18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRAS-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77).
CONCLUSIONS
This study provided a comprehensive understanding of the efficacy and safety of KRAS inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRAS inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRAS inhibitor treatment.
Topics: Humans; Kelch-Like ECH-Associated Protein 1; Proto-Oncogene Proteins p21(ras); NF-E2-Related Factor 2; Carcinoma, Non-Small-Cell Lung; Mutation; Lung Neoplasms
PubMed: 38185210
DOI: 10.1016/j.phrs.2024.107060 -
BMC Cancer Jan 2024Currently, the value of oral selective estrogen receptor degraders (SERDs) for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative... (Meta-Analysis)
Meta-Analysis
The value of oral selective estrogen receptor degraders in patients with HR-positive, HER2-negative advanced breast cancer after progression on ≥ 1 line of endocrine therapy: systematic review and meta-analysis.
BACKGROUND
Currently, the value of oral selective estrogen receptor degraders (SERDs) for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC) after progression on ≥ 1 line of endocrine therapy (ET) remains controversial. We conducted a meta-analysis to evaluate progression-free survival (PFS) and safety benefits in several clinical trials.
MATERIALS AND METHODS
Cochrane Library, Embase, PubMed, and conference proceedings (SABCS, ASCO, ESMO, and ESMO Breast) were searched systematically and comprehensively. Random effects models or fixed effects models were used to assess pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for treatment with oral SERDs versus standard of care.
RESULTS
A total of four studies involving 1,290 patients were included in our analysis. The hazard ratio (HR) of PFS showed that the oral SERD regimen was better than standard of care in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET (HR: 0.75, 95% CI: 0.62-0.91, p = 0.004). In patients with ESR1 mutations, the oral SERD regimen provided better PFS than standard of care (HR: 0.58, 95% CI: 0.47-0.71, p < 0.00001). Regarding patients with disease progression following previous use of CDK4/6 inhibitors, PFS benefit was observed in oral SERD-treatment arms compared to standard of care (HR: 0.75, 95% CI: 0.64-0.87, p = 0.0002).
CONCLUSIONS
The oral SERD regimen provides a significant PFS benefit compared to standard-of-care ET in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET. In particular, we recommend oral SERDs as a preferred choice for those patients with ESR1m, and it could be a potential replacement for fulvestrant. The oral SERD regimen is also beneficial after progression on CDK4/6 inhibitors combined with endocrine therapy.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Receptors, Estrogen; Antineoplastic Combined Chemotherapy Protocols; Fulvestrant; Estrogen Antagonists
PubMed: 38166684
DOI: 10.1186/s12885-023-11722-4 -
Journal of Immunotherapy (Hagerstown,... May 2024The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the...
Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Proto-Oncogene Proteins B-raf; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins c-ret; Receptor, ErbB-2
PubMed: 38112201
DOI: 10.1097/CJI.0000000000000500 -
Frontiers in Endocrinology 2023Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.
METHODS
Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.
RESULTS
In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.
CONCLUSION
This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.
Topics: Humans; Thyroid Cancer, Papillary; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Thyroid Neoplasms; Lymphatic Metastasis; Prevalence; Carcinoma, Papillary; Mutation
PubMed: 38047109
DOI: 10.3389/fendo.2023.1273498 -
International Journal of Molecular... Nov 2023Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample... (Meta-Analysis)
Meta-Analysis Review
Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample should be examined in assessing drug targets. This study systematically analyzed all the literature on primary melanoma and its matched metastasis. Following PRISMA guidelines, we searched multiple medical databases for relevant publications from January 2000 to December 2022, assessed the quality of the primary-level studies using the QUIPS tool, and summarized the concordance rate of the most reported genes using the random-effects model. Finally, we evaluated the inter-study heterogeneity using the subgroup analysis. Thirty-one studies investigated the concordance of and in 1220 and 629 patients, respectively. The pooled concordance rate was 89.4% [95% CI: 84.5; 93.5] for and 97.8% [95% CI: 95.8; 99.4] for . When high-quality studies were considered, only mutation status consistency increased. Five studies reported the concordance status of c (93%, 44 patients) and promoter (64%, 53 patients). Lastly, three studies analyzed the concordance of cancer genes involved in the signaling pathways, apoptosis, and proliferation, such as (25%, four patients), (44%, nine patients), and (20%, five patients). Our study found that the concordance of known drug targets (mainly ) during melanoma progression is higher than in previous meta-analyses, likely due to advances in molecular techniques. Furthermore, significant heterogeneity exists in the genes involved in the melanoma genetic makeup; although our results are based on small patient samples, more research is necessary for validation.
Topics: Humans; Melanoma; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Mutation; Melanoma, Cutaneous Malignant
PubMed: 38003476
DOI: 10.3390/ijms242216281 -
Medicine Nov 2023This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single neoadjuvant chemotherapy or endocrine therapy, specifically in the context of hormone receptor-positive (HR+) breast cancer treatment.
METHODS
We conducted a thorough literature search across several databases, including China National Knowledge Infrastructure, Wanfang, Weipu, Chinese Journal Full-text Database, PubMed, Web of Science, Cochrane Library, and EMBASE, adhering to the guidelines outlined in the PRISMA statement. Our specific focus was on identifying randomized controlled trials that directly compared the combined approach of neoadjuvant chemotherapy and endocrine therapy with single chemotherapy or endocrine therapy in the context of treating HR+ breast cancer. Subsequently, we utilized statistical packages implemented in R software to perform comparative analyses of key clinical indicators, encompassing the complete response, objective response rate (ORR), disease control rate, pathological complete response (pCR), and adverse reactions.
RESULTS
A total of 11 randomized controlled trials, involving 1359 patients, all of whom met our inclusion criteria and were thus included in our comprehensive analysis. Within this cohort, 688 patients (50.63%) administered neoadjuvant chemotherapy combined with endocrine therapy (NCET), 642 patients (47.24%) received neoadjuvant chemotherapy (NCT) alone, while 29 patients (2.13%) underwent neoadjuvant endocrine therapy (NET) alone. The results of our meta-analysis revealed that NCET exhibited a statistically significant enhancement in both ORR and pCR (P < .05). Nonetheless, when compared to NCT or NET, NCET did not yield a significant impact on complete response, disease control rate, and safety (P > .05). In addition, NCET demonstrated a significant improvement in ORR among patients with HR+, HER2-negative breast cancer (P < .05). However, it was also linked to a heightened incidence of serious adverse reactions within this particular patient subgroup (P < .05).
CONCLUSION
The combination of Neoadjuvant chemotherapy and endocrine therapy stands out as a significant contributor to enhancing the ORR and pCR for HR+ breast cancer patients. For breast cancer patients with HER2- status, NCET demonstrates a remarkable improvement in ORR but is also associated with the emergence of adverse reactions.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; China
PubMed: 37986364
DOI: 10.1097/MD.0000000000035928 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z -
British Journal of Cancer Mar 2024Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women.
METHODS
We conducted a systematic review and meta-analysis assessing the accuracy of HPV-E6/E7-oncoprotein tests to detect underlying cervical-precancer and cancer. We included studies reporting data on oncoprotein test accuracy detecting cervical intraepithelial neoplasia grade 3 or worse. Random effects logistic regression models were applied for pooling absolute and relative accuracy.
RESULTS
Twenty-two studies were included. Sensitivity and specificity estimates ranged from 54.2% (95%CI: 45.2-63.0) to 69.5% (95%CI:60.8-76.9) and from 82.8% (95%CI: 50.4-95.8) to 99.1 (95%CI: 98.8-99.3), respectively in the population irrespective of HPV status. Higher sensitivity estimates ranging from 60.8% (95%CI: 49.6-70.9) to 75.5% (95%CI: 71.7-78.9) but lower specificity estimates ranging from 83.7% (95%CI: 76.1-89.3) to 92.1% (95%CI: 88.5-94.6) were observed in studies enrolling high-risk-HPV-positive women. Studies recruiting only HIV-positive women showed a pooled sensitivity of 46.9% (95%CI: 30.6-63.9) with a specificity of 98.0% (95%CI: 96.8-98.7).
CONCLUSIONS
The high specificity of oncoprotein tests supports its use for triaging HPV-positive women. However, oncoprotein-negative women would not be recommended to undertake routine screening, requiring further follow-up. Large-scale and longitudinal studies are needed to further investigate the role of E6/E7-oncoprotein detection in predicting the risk of developing cervical pre-cancer and cancer.
Topics: Female; Humans; Papillomavirus Infections; Uterine Cervical Dysplasia; Oncogene Proteins, Viral; Cervix Uteri; Papillomavirus E7 Proteins; Uterine Cervical Neoplasms; Papillomaviridae
PubMed: 37973957
DOI: 10.1038/s41416-023-02490-w