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Journal of Personalized Medicine Feb 2024Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit... (Review)
Review
BACKGROUND
Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects.
RESULTS
Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%).
CONCLUSIONS
The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.
PubMed: 38541003
DOI: 10.3390/jpm14030261 -
The Cochrane Database of Systematic... Jul 2023Most people who are newly diagnosed with non-small cell lung cancer (NSCLC) have advanced disease. For these people, survival is determined by various patient- and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most people who are newly diagnosed with non-small cell lung cancer (NSCLC) have advanced disease. For these people, survival is determined by various patient- and tumor-related factors, of which the performance status (PS) is the most important prognostic factor. People with PS 0 or 1 are usually treated with systemic therapies, whereas people with PS 3 or 4 most often receive supportive care. However, treatment for people with PS 2 without a targetable mutation remains unclear. Historically, people with a PS 2 cancer are frequently excluded from (important) clinical trials because of poorer outcomes and increased toxicity. We aim to address this knowledge gap, as this group of people represents a significant proportion (20% to 30%) of the total population with newly diagnosed lung cancer.
OBJECTIVES
To identify the best first-line therapy for advanced lung cancer in people with performance status 2 without a targetable mutation or with an unknown mutation status.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 17 June 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared different chemotherapy (with or without angiogenesis inhibitor) or immunotherapy regimens, specifically designed for people with PS 2 only or studies including a subgroup of these people.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. overall survival (OS), 2. health-related quality of life (HRQoL), and 3. toxicity/adverse events. Our secondary outcomes were 4. tumor response rate, 5. progression-free survival, and 6. survival rates at six and 12 months' treatment. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 22 trials in this review and identified one ongoing trial. Twenty studies compared chemotherapy with different regimens, of which 11 compared non-platinum therapy (monotherapy or doublet) versus platinum doublet. We found no studies comparing best supportive care with chemotherapy and only two abstracts analyzing chemotherapy versus immunotherapy. We found that platinum doublet therapy showed superior OS compared to non-platinum therapy (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.57 to 0.78; 7 trials, 697 participants; moderate-certainty evidence). There were no differences in six-month survival rates (risk ratio [RR] 1.00, 95% CI 0.72 to 1.41; 6 trials, 632 participants; moderate-certainty evidence), whereas 12-month survival rates were improved for treatment with platinum doublet therapy (RR 0.92, 95% CI 0.87 to 0.97; 11 trials, 1567 participants; moderate-certainty evidence). PFS and tumor response rate were also better for people treated with platinum doublet therapy, with moderate-certainty evidence (PFS: HR 0.57, 95% CI 0.42 to 0.77; 5 trials, 487 participants; tumor response rate: RR 2.25, 95% CI 1.67 to 3.05; 9 trials, 964 participants). When analyzing toxicity rates, we found that platinum doublet therapy increased grade 3 to 5 hematologic toxicities, all with low-certainty evidence (anemia: RR 1.98, 95% CI 1.00 to 3.92; neutropenia: RR 2.75, 95% CI 1.30 to 5.82; thrombocytopenia: RR 3.96, 95% CI 1.73 to 9.06; all 8 trials, 935 participants). Only four trials reported HRQoL data; however, the methodology was different per trial and we were unable to perform a meta-analysis. Although evidence is limited, there were no differences in 12-month survival rates or tumor response rates between carboplatin and cisplatin regimens. With an indirect comparison, carboplatin seemed to have better 12-month survival rates than cisplatin compared to non-platinum therapy. The assessment of the efficacy of immunotherapy in people with PS 2 was limited. There might be a place for single-agent immunotherapy, but the data provided by the included studies did not encourage the use of double-agent immunotherapy.
AUTHORS' CONCLUSIONS
This review showed that as a first-line treatment for people with PS 2 with advanced NSCLC, platinum doublet therapy seems to be preferred over non-platinum therapy, with a higher response rate, PFS, and OS. Although the risk for grade 3 to 5 hematologic toxicity is higher, these events are often relatively mild and easy to treat. Since trials using checkpoint inhibitors in people with PS 2 are scarce, we identified an important knowledge gap regarding their role in people with advanced NSCLC and PS 2.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Lung Neoplasms; Mutation
PubMed: 37419867
DOI: 10.1002/14651858.CD013382.pub2 -
International Journal of Radiation... Feb 2024Thoracic radiation therapy (RT) for non-small cell lung cancers may overcome resistance to tyrosine kinase inhibitors (TKIs). However, the risk of severe... (Meta-Analysis)
Meta-Analysis Review
Treatment-Related Pneumonitis of EGFR Tyrosine Kinase Inhibitors Plus Thoracic Radiation Therapy in Patients With Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
Thoracic radiation therapy (RT) for non-small cell lung cancers may overcome resistance to tyrosine kinase inhibitors (TKIs). However, the risk of severe treatment-related pneumonitis (TRP) is a major concern, and the results of the combined treatment remain controversial. Therefore, we aimed to systematically review existing publications and provide a meta-analysis of TRP from a combined therapy of thoracic RT and TKIs. A systematic literature review was performed using the PubMed-MEDLINE and Embase databases to identify eligible publications. The number of severe TRP cases of grade 3 or higher was extracted and then analyzed by fixed or randomized model meta-analysis. Heterogeneity tests were performed using the I² and τ² statistics. Subgroup analyses were conducted on the types of RT and the sequence of the combined treatment. Our literature search identified 37 eligible studies with 1143 patients. Severe TRP occurred in 3.8% (95% CI, 1.8%-6.5%) of patients overall, and fatal pneumonitis occurred rarely in 0.1% (95% CI, 0.0%-0.3%). In the subgroup analysis, the severe TRP proportion was 2.3% (95% CI, 1.0%-4.1%) for patients under definitive (chemo)RT (19 studies, n = 702) versus 2.9% (95% CI, 1.3%-5.1%) for patients who received local stereotactic body RT or palliative RT (15 studies, n = 361). The severe TRP rate was 4.9% (95% CI, 2.4%-8.1%) for concurrent TKI and RT (26 studies, n = 765), which was significantly higher than TRP of 0.4% (95% CI, 0.0%-3.1%) for sequential therapy (6 studies, n = 200). Our meta-analysis showed that combined thoracic RT and epidermal growth factor receptor-TKI therapy has an acceptable risk of severe TRP and rare mortality in patients with non-small cell lung cancers. Concurrent treatment is less tolerable and should be administered with caution. Further investigations using osimertinib are required as the data on its effects are limited.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; ErbB Receptors; Pneumonia; Mutation
PubMed: 37716460
DOI: 10.1016/j.ijrobp.2023.09.009 -
Journal of Neuropathology and... Apr 2024SMARCA4 alterations can be encountered in a variety of human neoplasms, and metastases to the central nervous system (CNS) are rare, offering a challenge to...
SMARCA4 alterations can be encountered in a variety of human neoplasms, and metastases to the central nervous system (CNS) are rare, offering a challenge to neuropathologists despite not representing a distinct diagnostic entity. To better understand the clinical and histologic presentation of such neoplasms, we report an observational case series and systematic review of 178 unique articles that yielded 15 published cases and 7 cases from institutional files. In the systematic review, the median age was 58 years, the male-to-female ratio was 2:1, and the most common diagnosis was lung adenocarcinoma; all CNS metastases were discovered within 1 year of presentation. In the case series, the median age was 58 years, the male-to-female ratio was 6:1, and all known metastases originated from the lung. Most patients had a smoking history and died of disease. GATA-3 positivity was seen in most case series examples. Concurrent TP53 mutations (83.3%) and a high tumor mutation rate (60%) were common. To our knowledge, this is the only case series and systematic review in the English literature aimed at assessing SMARCA4-altered metastases in the CNS and vertebral column. We highlight the challenges of neuropathologic evaluation of such tumors and provide observational evidence of early metastases, histologic appearances, and immunohistochemical findings, including previously unreported GATA-3 positivity.
PubMed: 38687619
DOI: 10.1093/jnen/nlae039 -
Therapeutic Advances in Medical Oncology 2024Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of... (Review)
Review
BACKGROUND
Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes.
METHODS
A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC.
RESULTS
In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months.
CONCLUSIONS
, and -altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. G12C mutation, non-V600E mutation, and amplification have better responses to immunotherapy, and more prospective studies are needed for further research.
PubMed: 38420602
DOI: 10.1177/17588359231225036 -
Tumori Oct 2023Patients whose tumours harbour epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) driver mutations can benefit most from treatment with... (Meta-Analysis)
Meta-Analysis Review
Patients whose tumours harbour epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) driver mutations can benefit most from treatment with tyrosine kinase inhibitors (TKIs). Most trials with immune checkpoint inhibitors (ICIs) included few patients whose tumour had oncogenic driver alterations. We therefore performed a meta-analysis of studies reporting the activity of ICIs in oncogene addicted NSCLC. A comprehensive search of MEDLINE, The Cochrane Library and EMBASE was conducted to identify relevant studies published up to 31 January 2021. The primary outcomes were median overall survival (OS); the secondary endpoints were progression-free survival and overall response rate (PFS and ORR). Overall, 46 studies were screened and selected for final analysis. The pooled ORR was 14.5% (95% CI 9.6-21.2%). The median pooled PFS in EGFR/ALK mutated cases was 3.9 months (95% CI 3-5.2 months). Median pooled OS was 10.7 months (95% CI 9.2-12.5 months). All registration trials in second line did not show any benefit of immunotherapy for the subgroup of patients with EGFR-mutated or ALK-rearranged tumours. The unsatisfied benefit of immunotherapy in oncogene-addicted tumours has been debated and is mainly due to the lower mutation burden of these neoplasms. Our data do not support the use of immunotherapy in the setting of oncogene actionable tumours. More data are needed to confirm or reject the benefit of the combination of TKIs with ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; ErbB Receptors; Mutation; Progression-Free Survival; Protein Kinase Inhibitors
PubMed: 36165425
DOI: 10.1177/03008916221122601 -
Heliyon Jun 2024FBXW7 is a tumour suppressor gene that functions as E3-ubiquitin-ligase, targeting numerous oncoproteins for degradation, i.e., Cyclin-E, c-Myc, and Notch. FBXW7...
UNLABELLED
FBXW7 is a tumour suppressor gene that functions as E3-ubiquitin-ligase, targeting numerous oncoproteins for degradation, i.e., Cyclin-E, c-Myc, and Notch. FBXW7 performs a pivotal role in regulating cell cycle progression. FBXW7 mutation is frequently implicated in various cancers.
METHODOLOGY
A systematic review and meta-analysis done on several studies using "Preferred Reporting Items for Systemmatic Reviews and Meta-Analysis (PRISMA)" criteria and registered with PROSPERO (registration-number-CRD42023388845). The preliminary search comprises 1182 articles; however, 58 studies were subsequently chosen after eliminating non-eligible studies. To explore the prevalence of FBXW7 mutation among colorectal cancer patients, data were analysed using "OpenMeta Analyst and comprehensive meta-analysis-3.0 (CMA-3.0)" software.
RESULTS
This meta-analysis involves 13,974 respondents; most were males 7825/13,974, (56.0 %). Overall prevalence of FBXW7 mutations was 10.3 %, (95%CI: 8.6-12.4), I2 = 90.5 %, (P < 0.001). The occurrence of FBXW7 mutations was highest in Russia [19.0 %, (95%CI: 9.8-33.7)] and Taiwan [18.8 %, (95%CI: 8.7-35.9)], P-values< 0.05 while the least prevalence was reported in Netherland (4 %) and Italy (5 %), both P-values< 0.001. Overall prevalence of FBXW7 abberation was greatest amongst male gender: "53.9 %, (95%CI: 8.3-62.0 %)", Tumour location (colon): 59.8 %, (95%CI: 53.9-65), tumour site (left): 61.6 %, (95%CI: 53.8-68.9), Tumour-grade (Moderate): 65.9 %, (95%CI: 54.9-75.4 %), and Tumour late-stage: 67.9 %, (95%CI: 49.7-84.3 %), all P-values< 0.001. When stratified according to study-period, an increasing trend was noted from 2018 till present with the highest mutation rate recorded in 2022 (15.3 %).
CONCLUSION
Overall prevalence of FBXW7 mutations was 10.3 % with male gender, left side, and late-stage being most mutated, and these outcomes conform with severally published articles on FBXW7 mutation.
PubMed: 38845996
DOI: 10.1016/j.heliyon.2024.e31471 -
Pancreatology : Official Journal of the... Feb 2024Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high sensitivity for the pathological diagnosis of pancreatic masses, but also a high false-negative rate.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high sensitivity for the pathological diagnosis of pancreatic masses, but also a high false-negative rate. K-ras gene mutations occur in over 75 % of pancreatic ductal adenocarcinomas (PDAC), and this meta-analysis evaluated the utility of detecting K-ras gene mutations from EUS-TA specimens for the diagnosis of PDAC.
METHODS
Relevant studies in PubMed, the Cochrane Library, and Web of Science were systematically searched. Meta-analysis was performed on data from the selected studies using a bivariate model to provide pooled values of sensitivity, specificity, and their 95 % confidence intervals (CIs).
RESULTS
This meta-analysis included 1521 patients (from 10 eligible studies) who underwent EUS-TA with K-ras gene mutation analysis for diagnosis of pancreatic solid masses. The pooled estimates of sensitivity and specificity were 76.6 % (95 % CI, 70.9-81.5 %) and 97.0 % (95 % CI, 94.0-98.5 %), respectively, for pathological diagnosis, 75.9 % (95 % CI 69.5-81.4 %) and 95.3 % (95 % CI, 92.3-97.2 %) for K-ras gene mutation analysis, and 88.7 % (95 % CI 87.1-91.7 %) and 94.9 % (95 % CI, 91.5-97.0 %) for pathological diagnosis in combination with K-ras gene mutation analysis. The sensitivity for diagnosis of PDAC was significantly higher for pathological diagnosis in combination with K-ras gene mutation analysis than for pathological diagnosis or K-ras gene mutation analysis alone (both, p < 0.001). There was no difference in specificity between pathological diagnosis in combination with K-ras gene mutation analysis and both either (p = 0.234, 0.945, respectively).
CONCLUSIONS
K-ras gene mutation analysis in combination with to pathological diagnosis of EUS-TA increases the accuracy of differential diagnosis of PDAC.
Topics: Humans; Pancreatic Neoplasms; Genes, ras; Adenocarcinoma; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Carcinoma, Pancreatic Ductal; Mutation
PubMed: 38042675
DOI: 10.1016/j.pan.2023.11.012 -
BMC Cancer Aug 2023To determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely... (Meta-Analysis)
Meta-Analysis
Rational application of EGFR-TKI adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant NSCLC: a systematic review and meta-analysis of 11 randomized controlled trials.
PURPOSE
To determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant non-small-cell lung cancer (NSCLC).
METHOD
Randomized controlled trials (RCTs) that compared the survival outcomes between adjuvant EGFR-TKIs and adjuvant chemotherapy or a placebo, or between different EGFR-TKI treatment durations for resected NSCLC, were eligible for inclusion. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effective measures using random-effect or fixed-effect models. Subgroup analysis was also performed.
RESULTS
Eleven RCTs involving 2102 EGFR-mutant NSCLC patients with or without EGFR-TKI adjuvant therapy were included. For all stage IB-IIIA NSCLC patients, EGFR-TKIs adjuvant therapy could not only significantly improve DFS (HR 0.43, 95% CI 0.30-0.63, P < 0.001) and 2- and 3-year DFS rates, but also improve OS (HR 0.72, 95% CI, 0.54-0.96, P = 0.024), compared with chemotherapy or the placebo. Further subgroup analyses indicated prolonged OS from first-generation EGFR-TKI adjuvant therapy in stage III patients, compared with chemotherapy or the placebo (HR for OS, 0.34; 95% CI, 0.18-0.63; P = 0.001). Of note, osimertinib adjuvant therapy led to the OS benefit expanding from stage III to stage II-III patients, with significantly improved DFS and a lower risk of brain recurrence, compared with the placebo. A 2-year treatment duration with EGFR-TKI adjuvant therapy showed a significantly lower recurrence risk than a ≤ 1-year duration.
CONCLUSION
The DFS advantage from first-generation EGFR-TKI adjuvant therapy can translate into an OS benefit in stage III NSCLC patients. Osimertinib might be more suitable for adjuvant therapy than first-generation EGFR-TKIs, because of the lower recurrence rate and the potential OS benefit even in early-stage patients. The optimal treatment duration for EGFR-TKIs at different stages of disease needs to be validated.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein Kinase Inhibitors; ErbB Receptors; Randomized Controlled Trials as Topic; Mutation
PubMed: 37528390
DOI: 10.1186/s12885-023-11194-6 -
Clinical Breast Cancer Jul 2024Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the... (Meta-Analysis)
Meta-Analysis
Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the application of PARPi in neoadjuvant therapy, but failed to reach a unified conclusion. PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase, and key oncological meetings for trials were searched for studies reporting neoadjuvant regimens with PARPi in HER2-negative breast cancer. Pathological complete response (pCR), residual cancer burden (RCB), breast-conservation surgery rate (BCSR), clinical response, and adverse events were extracted and pooled in a meta-analysis using the Mantel Haenszel random/fixed effects model. Subgroup analyses of pCR were conducted according to BRCA1/2 status, and hormone receptor (HR) status. Five studies (N = 1223) were included, the addition of PARPi to neoadjuvant regimens significantly increased pCR rates (HR 1.45, 95%CI 1.09-1.92, P = .01, I = 86%). In subgroup analysis, the addition of PARPi increased the pCR rate both in HR-positive (n = 383) and HR-negative (n = 431) subgroups, which showed a dominant effect of PARPi regardless of HR status (HR 2.07, 95%CI 1.33-3.23, P = .001, I = 0%; HR 1.85, 95%CI 1.39-2.26, P < .0001, I = 0%, respectively). However, when we performed a subgroup analysis based on the status of BRCA1/2, no further benefit for PARPi was found. Adverse reactions were generally tolerable. Other outcome indexes, including RCB, clinical response, BCSR, and PARPi did not show a clinical benefit. Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Neoadjuvant Therapy; Poly(ADP-ribose) Polymerase Inhibitors; Receptor, ErbB-2; Treatment Outcome
PubMed: 38580572
DOI: 10.1016/j.clbc.2024.02.020