Trastuzumab combined with doublet or single-agent chemotherapy as first-line therapy for HER2-positive metastatic breast cancer

Purpose

To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC).

Methods

We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766.

Results

The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63–0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88–0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98–1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H.

Conclusions

Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

     

Continuous versus intermittent chemotherapy strategies in metastatic colorectal cancer: a systematic review and meta-analysis

There are no clinically significant survival differences between continuous and intermittent strategies of delivering chemotherapy for first-line metastatic colorectal cancer. Intermittent strategies should be part of an informed discussion of treatment options with patients with untreated metastatic colorectal cancer.BackgroundAn important goal of intermittent strategies of delivering systemic treatment as first-line treatment of metastatic colorectal cancer (mCRC) is to maintain efficacy while improving patients' quality of life (QoL). Given the varying impact on efficacy demonstrated in individual randomized, controlled trials (RCTs), a systematic review and meta-analysis of RCTs of these intermittent strategies was carried out.DesignRelevant databases were systematically searched for the period 2000–2014. RCTs that compared a continuous versus intermittent strategy of delivering systemic treatment were identified by a systematic review. Overall survival (OS) hazard ratios (HRs) were extracted from the most recently reported trial results. The results of identified trials were clinically homogeneous so the data were pooled using Review Manager software (RevMan 5.1).ResultsEleven RCTs were identified (n = 4 854). For the eight (n = 4508) trials with available HRs, the treatment patients received after induction was: none (five trials,n = 3036), fluoropyrimidine (one trial,n = 620), and biologic (two trials,n = 852). There were no statistically significant survival differences observed between the continuous and intermittent chemotherapy strategies. There was no statistically significant difference observed between continuous and intermittent strategies [HR = 1.03, 95% confidence interval (CI) 0.96–1.10,P = 0.38)]. Subgroup analyses demonstrated results were generally robust across induction and maintenance regimens. One subgroup analysis of the three trials (CAIRO3, OPTIMOX2, COIN,n = 2403) with combination treatment induction and no maintenance until progression revealed a statistically, but nonclinically significant benefit for continuous treatment (HR = 1.10, 95% CI 1.00–1.20,P = 0.049). QoL life was either the same in both arms in two trials (n = 912) or improved in the intermittent strategy arm in one trial (n = 1630).ConclusionIntermittent strategies of delivering systemic treatment of mCRC do not result in a clinically significant reduction in OS compared with a continuous strategy of delivery, and should be part of an informed discussion of treatment options with patients with mCRC.     

Second-line therapy for metastatic urothelial carcinoma: Defining the best treatment option among immunotherapy,chemotherapy, and antiangiogenic targeted therapies. A systematic review and meta-analysis

There is no second-line standard of care universally accepted for platinum-refractory metastatic urothelial carcinoma. Immunotherapy and anti-VEGF(R) targeted therapies are 2 emerging strategies with promising though inconclusive results. We perform a systematic meta-analysis to assess the available options. We searched MEDLINE/PubMed, the Cochrane Library, and American society of clinical oncology (ASCO) Meeting abstracts to identify prospective studies. Data extraction was conduced according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The measured outcomes were overall survival (OS) and progression free survival (PFS). Seven randomized controlled trials were selected for final analysis, with a total of 2,451 evaluable patients. Chemotherapy with vinflunine did not reduce the risk of progression (HR?=?1.11; 95%CI 0.78–1.57; P = .56) or death (HR?=?0.97; 95%CI 0.70–1.34; P?=?.87) compared to taxanes. Immunotherapy with anti-PD-1/PD-L1 mAb improved OS over chemotherapy (HR?=?0.81; 95% CI 0.71–0.92; P<.0009). The OS benefit of immunotherapy was retained when compared to taxanes, but not compared to vinflunine, although without a significant difference between the 2 subgroups (P?=?.30). A lack of PFS (HR?=?0.73; P?=?.08) and OS (HR?=?1.0; P?=?.99) benefit was observed with an anti-VEGF(R) plus chemotherapy compared to chemotherapy alone. No PFS (P?=?.14) or OS (P?=?.13) differences were detected when comparing anti-VEGF(R) ± chemotherapy and immunotherapy. Immunotherapy significantly improved OS compared to chemotherapy in metastatic urothelial carcinoma unselected for PD-L1 status. The addition of anti-VEGF(R) to chemotherapy did not provide any statistically significant benefit in terms of PFS or OS. Single agent taxanes or vinflunine can be considered given their similar efficacy but different toxicity profiles.     

Second-line chemotherapy in metastatic docetaxel-resistant prostate cancer: a review

The results of cytotoxic therapy in the second-line setting of metastatic castration-resistant prostate cancer have demonstrated that disease is poorly controlled after taxane resistance with a time to progression of 3 months or less. Many trials of second-line chemotherapy have been disappointing. However, most of patients with docetaxel-pretreated castration-resistant disease receive a second-line chemotherapy. Molecular mechanism of castration resistance and docetaxel resistance is resumed, and clinical trials of second-line chemotherapy after docetaxel progression are reviewed. Reintroduction of docetaxel after a drug-free interval is an active treatment in docetaxel-pretreated patients, and only recently a prospective study documented a survival benefit of 2.4 months after second-line taxane-based chemotherapy of metastatic docetaxel-resistant prostate cancer. Although a second-line chemotherapy with a taxane could improve overall survival, a change of biology of castration-resistant prostate cancer after docetaxel is suggested, as inferred by the renewed hormonal sensitivity, whose role on survival remains unknown, and from the activity of antiangiogenic drugs.     

Second-line chemotherapy in advanced biliary cancer: a systematic review

The randomized NCRN phase III ABC-02 trial provided level-A evidence for first-line chemotherapy with cisplatin and gemcitabine combination in advanced biliary cancer (ABC). This systematic literature review aims to evaluate the level of evidence for the use of second-line chemotherapy for patients with ABC in terms of overall survival (OS), response, toxicity and quality of life. Eligible studies were identified using Medline, ASCO, ESMO and the World Gastrointestinal Congress databases. Searches were last updated on 15 December 2013. Eligible studies reported survival and/or response data for patients with ABC receiving second-line systemic chemotherapy. This systematic review was registered in the PROSPERO database (No. CRD42013004205). Five hundred and fifty-eight studies were identified from the searches in Medline (n = 342), ASCO (n = 160), ESMO (n = 27) and World Gastrointestinal Congress (n = 29). Twenty-five studies were eligible: 14 phase II clinical trials, 9 retrospective analyses and 2 case reports. In total, data from 761 patients were reported with median number of patients included in each study of 22 (range 9–96). The mean OS was 7.2 months [95% confidence interval (CI) 6.2–8.2] [phase II: 6.6 (95% CI 5.1–8.1); retrospective analysis: 7.7 (95% CI 6.5–8.9)]. The mean progression-free survival (PFS), response rate (RR) and disease control rate were 3.2 months (95% CI 2.7–3.7), 7.7% (95% CI 4.6–10.9) and 49.5% (95% CI 41.4–57.7), respectively. The best correlations were between OS and PFS for all studies (r = 0.54; P = 0.01) and between OS and PFS (r = 0.61; P = 0.04) and OS and RR (r = 0.62; P = 0.03) for phase II studies, respectively. Biliary tract cancer is known to be a chemo-responsive disease. There is insufficient evidence (level C) to recommend a second-line chemotherapy schedule in ABC, although the available data suggest that a cohort of patients may benefit. Further prospective and randomized studies are needed to clarify the relative value of second-line chemotherapy in this setting.     

Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a meta-analysis

BackgroundMany patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care.Patients and methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013.ResultsThe search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001] was observed with salvage chemotherapy.When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel.ConclusionThis meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.     

Second-line chemotherapy for small-cell lung cancer: a review

Small-cell lung cancer (SCLC) is an aggressive malignancy, and only a minority of patients survive 2 years. Although this cancer is sensitive to both chemotherapy and radiotherapy, the majority of patients relapse, and second-line treatment is an option for many. Currently in the United States, the combination of cisplatin/etoposide is the standard first-line therapy in SCLC. At this time, topotecan is the only Food and Drug Administration-approved chemotherapeutic agent for second-line treatment of SCLC. In this paper, we review studies of second-line chemotherapy for SCLC.     

贝伐单抗联合化疗一线治疗转移性结直肠癌有效性和安全性的系统评价

目的:系统评价贝伐单抗(bevacizumab, BEV)联合化疗一线治疗转移性结直肠癌的有效性和安全性.方法:利用计算机检索PubMed、Embase、Cochrane图书馆、中国期刊全文数据库、中国生物医学文献数据库和中文科技期刊全文数据库中的BEV联合化疗一线治疗转移性结直肠癌的随机对照试验,对纳入研究的方法学质量进行评价,并进行荟萃分析.结果:共纳入6篇文献,包括2 646名患者.荟萃分析结果显示,BEV联合化疗组的有效率(完全缓解+部分缓解)较高(相对危险度为1.27,95%的可信区间为1.00～1.61,P= 0.05),且中位生存时间和无进展生存(progression-free survival, PFS)时间延长.治疗组与对照组总的3/4级不良反应、3/4级高血压、不良反应所致研究中止以及胃肠穿孔发生率的差异均有统计学意义,其相对危险度(95%的可信区间)分别为1.12(1.07～1.61)、4.51(2.81～7.23)、1.37(1.16～1.63)和4.32(1.24～15.05);而3/4级出血、60 d全因死亡率、3/4级蛋白尿、3/4级腹泻、3/4级白细胞减少和肺栓塞的发生率差异则无统计学意义,其相对危险度(95%的可信区间)分别为1.50(0.87～2.57)、0.71(0.45～1.11)、2.26(0.69～7.33)、1.18(0.99～1.41)、1.17(0.97～1.42)和0.84(0.46～1.53). 结论:BEV联合化疗一线治疗转移性结直肠癌可提高有效率,延长PFS和中位生存时间,但总的3/4级不良反应、3/4级高血压和胃肠穿孔的发生率较高.     

含铂双药对比非铂单药二线治疗晚期非小细胞肺癌的系统评价

目的系统评价联合铂类的双药方案和非铂类单药方案二线治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的有效性及安全性。方法计算机检索PubMed、The Cochrane Library、Web of science、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)和万方数据库,收集含铂双药化疗方案对比非铂单药化疗方案二线治疗晚期NSCLC的随机对照试验,用RevMan 5.2进行荟萃分析。结果最终纳入11项临床随机对照试验,共1 167例患者。Meta分析结果显示,与非铂单药方案相比,含铂双药方案化疗可提高晚期NSCLC患者的化疗客观有效率(overall response rate,ORR)及疾病控制率(disease control rate,DCR),分别为1.43倍(RR=1.43,95%CI为1.08~1.89,P=0.010)和1.16倍(RR=1.16,95%CI为1.05~1.27,P=0.002)。同时,含铂双药方案化疗亦可延长晚期NSCLC患者的无进展生存期(progression-free survival,PFS),HR=0.74,95%CI为0.58~0.95,P=0.020;但含铂双药化疗与非铂单药化疗组1年生存率差异无统计学意义,RR=1.21,95%CI为0.91~1.61,P=0.190。安全性方面,含铂双药方案化疗最主要的不良反应为血小板减少,RR=2.99,95%CI为1.95~4.59,P<0.001;而3~4级白细胞减少、中性粒细胞减少、恶心呕吐和贫血等不良反应,含铂双药化疗与非铂单药化疗组差异均无统计学意义。结论与非铂单药化疗方案相比,含铂双药方案可提高晚期NSCLC患者化疗ORR及DCR,延长晚期NSCLC患者的PFS,但不能明显改善1年生存率。最主要不良反应为血小板减少,低毒耐受性好。因此,含铂双药化疗方案在一线治疗失败的晚期NSCLC患者的二线治疗中值得进一步推广。     

Vaccine therapy for metastatic melanoma: systematic review and meta-analysis of clinical trials

Clinical trials of melanoma vaccines have yielded inconclusive data on whether a positive melanoma-specific immune response predicts treatment benefit. The objective of this study was to evaluate the effect of different melanoma vaccine strategies and the association between immunologic response and survival. The authors conducted a systematic review and meta-analysis of phase II and III clinical trials of melanoma vaccine. Outcomes assessed included overall disease control, overall survival, and impact on immune response. For binary variables, proportions were reported for one-arm studies and risk ratios for controlled studies. For survival data, medians were reported for one-arm studies and hazard ratios for controlled studies. The existence and extent of heterogeneity between trials was evaluated using Cochran's Q statistic. A two-sided P value of less than 0.05 for meta-analysis results was considered statistically significant. Of 56 studies reporting data on 4375 patients, overall disease control was seen in 25.3% [95% confidence interval (CI): 20.7-30.5%] of patients. Subgroup analysis revealed that overall disease control for peptide vaccines plus interleukin-2 (IL-2) was improved compared with interleukin-2 alone (pooled risk ratio: 2.79, 95% CI: 1.62-4.80). Overall survival varied among six studies comparing vaccine with other treatments. Subgroup analysis revealed that tumor-specific immune response was associated with prolonged overall survival compared with the lack of response (pooled hazard ratio: 2.15, 95% CI: 1.88-2.44). Severe toxicity associated with vaccine treatment was uncommon. Overall, a melanoma-specific immune response predicted longer overall survival, although no evidence was found that vaccine therapy provides better overall disease control or overall survival compared with other treatments.     

Second-line therapy for castrate-resistant prostate cancer: a literature review

Despite a survival benefit in the first-line treatment of castrate-resistant prostate cancer (CRPC) with docetaxel, the prognosis remains limited. There are increasing options available for patients with CRPC in the second-line setting, but there is currently little consensus regarding the optimal treatment. There have been numerous phase II and retrospective studies examining second-line options in CRPC, including retreatment with docetaxel, mitoxantrone, cyclophosphamide and carboplatin, which can be associated with meaningful responses in a significant minority of patients. In 2010 three randomized trials were published or presented which demonstrated a survival benefit in the second-line setting. These included cabazitaxel compared with mitoxantrone, sipuleucel-T (immunotherapy) and abiraterone acetate versus placebo. Ongoing research in the second-line setting of CRPC to optimize treatment options, with the objectives of survival prolongation, improvement in quality of life and pain management, is still needed.     

Combining of chemotherapy with targeted therapy for advanced biliary tract cancer: A systematic review and meta-analysis

BACKGROUNDTargeted therapy (TT) has resulted in controversial efficacy as first-line treatment for biliary tract cancer (BTC). More efficacy comparisons are required to clarify the overall effects of chemotherapy (CT) combined with TT and CT alone on advanced BTC.AIMTo conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODSThe PubMed, EMBASE, ClinicalTrials, Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022. Only randomized clinical trials (RCTs) including comparisons between the combination of gemcitabine-based CT with TT and CT alone as first-line treatment for advanced BTC were eligible (PROSPERO-CRD42022313001). The odds ratios (ORs) for the objective response rate (ORR) and hazard ratios (HRs) for both progression-free survival (PFS) and overall survival (OS) were calculated and analyzed. Subgroup analyses based on different targeted agents, CT regimens and tumor locations were prespecified.RESULTSNine RCTs with a total of 1361 individuals were included and analyzed. The overall analysis showed a significant improvement in ORR in patients treated with CT + TT compared to those treated with CT alone (OR = 1.43, 95%CI: 1.11-1.86, P = 0.007) but no difference in PFS or OS. Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor (OR = 1.67, 95%CI: 1.17-2.37, P = 0.004) but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor. Notably, patients who received a CT regimen of gemcitabine + oxaliplatin in the CT + TT arm had both a higher ORR (OR = 1.75, 95%CI: 1.20-2.56, P = 0.004) and longer PFS (HR = 0.83, 95%CI: 0.70-0.99, P = 0.03) than those in the CT-only arm. Moreover, patients with cholangiocarcinoma treated with CT + TT had significantly increased ORR and PFS (ORR, OR = 2.06, 95%CI: 1.27-3.35, PFS, HR = 0.79, 95%CI: 0.66-0.94).CONCLUSIONCT + TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes, and highlighting the importance of CT regimens and tumor types in the application of TT.     

Second-line treatment for advanced non-small cell lung cancer: a systematic review

BACKGROUND: Among advanced non-small cell lung cancer (NSCLC) patients, most will resist or relapse after first-line chemotherapy. As a result, second-line therapy has been a major focus for clinical research. MATERIALS AND METHODS: A systematic review was carried out from 1996 to February 2005. RESULTS: Second-line chemotherapy provides pre-treated NSCLC patients with a clear survival advantage. Docetaxel 75 mg/m(2) every 3 weeks is the present standard second-line chemotherapy. Despite promising results regarding efficacy and toxicity in phase III studies, a docetaxel weekly schedule could not be recommended. Pemetrexed recently emerged as an alternative with similar efficacy and less toxicity. Although the combination of two drugs was not associated with a survival benefit when compared with single-agent chemotherapy, such regimens induced a dramatic increase in toxicities and therefore mono-chemotherapy remains the standard as second-line therapy. Finally, few new agents were reported with better results than those used previously and clinical research on second-line therapy currently focuses on combinations with targeted therapies. CONCLUSION: Second-line chemotherapy offers NSCLC patients a small but significant survival improvement. However, this field of clinical research needs further investigations in order to answer certain remaining questions especially concerning targeted therapies.     

Short-term outcomes of neoadjuvant hormonal therapy versus neoadjuvant chemotherapy in breast cancer: systematic review and meta-analysis of randomized controlled trials

Introduction: Estrogen receptor positive (ER⁺) breast cancer (BC) is highly hormonal therapy-responsive. The choice between neoadjuvant hormonal therapy (NHT) and neoadjuvant chemotherapy (NCT) remains controversial. The aim of this meta-analysis was to evaluate benefits and safety of NHT compared with NCT for operable BC patients.

Areas covered: Electronic databases were searched to identify randomized clinical trials (RCTs) comparing NHT and NCT for treatment of invasive and immunohistochemically ER⁺ BC. Major outcomes were clinical response rate, pathologic complete response (pCR), operation methods, recurrence, and adverse events. Five RCTs were included. The clinical response rates between NHT and NCT were not statistically different overall, or in ER-rich patients or postmenopausal women. Compared with NCT, NHT had a significant reduction of complete response rate and an increment in progressive disease rate. NHT increased rates of breast conserving surgery (BCS) and wide local excision (WLE) compared with NCT. All the other parameters were comparable. Patients receiving NHT had better tolerance than those undergoing NCT.

Expert commentary: When treating BC, NHT was well tolerated, and contributed to more BCS and WLE cases, especially in ER-rich postmenopausal patients. While for those who are eligible for chemotherapy, NCT might be better recommended due to higher response rates.     

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

BackgroundThe role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.Material and methodsA systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).ResultsNine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.ConclusionIn TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.PROSPERO registration numberCRD42018080042.     

Racial disparities in chemotherapy administration for early-stage breast cancer: a systematic review and meta-analysis

Background

MicroRNAs constitute a large family of non-coding RNAs, which actively participate in tumorigenesis by regulating a set of mRNAs of distinct signaling pathways. An altered expression of these molecules has been found in different tumorigenic processes of breast cancer, the most common type of cancer in the female population worldwide.

Purpose

The objective of this review is to discuss how miRNAs become master regulators in breast tumorigenesis.

Methods

An integrative review of miRNAs and breast cancer literature from the last 5 years was done on PubMed. We summarize recent works showing that the defects on the biogenesis of miRNAs are associated with different breast cancer characteristics. Then, we show several examples that demonstrate the link between cellular processes regulated by miRNAs and the hallmarks of breast cancer. Finally, we examine the complexity in the regulation of these molecules as they are modulated by other non-coding RNAs and the clinical applications of miRNAs as they could serve as good diagnostic and classification tools.

Conclusion

The information presented in this review is important to encourage new directed studies that consider microRNAs as a good tool to improve the diagnostic and treatment alternatives in breast cancer.

     

含铂双药与非铂类单药一线治疗老年晚期NSCLC对比研究的Meta分析

目的:对联合铂类的双药方案和非铂类单药方案一线治疗老年晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的有效性及安全性进行Meta分析。方法:计算机检索PubMed、EMbase、Cochrane Library、中国期刊全文数据库(CNKI)和中国生物医学文献数据库(CBMdice),收集以含铂双药方案对比非铂单药方案治疗老年晚期NSCLC的随机对照试验,用RevMan5.2软件对数据进行Meta分析。结果:共纳入12项随机对照试验(753例病例),Meta分析结果显示,与非铂单药方案相比,含铂双药方案化疗可提高老年晚期NSCLC患者的化疗客观有效率1.37倍,两者差异有统计学意义(RR=1.37,95%CI:1.12～1.69,P=0.002),但两组1年生存率差异无统计学意义,RR=1.07,95%CI:0.91～1.27,P=0.41;并且含铂双药组更易发生3～4级白细胞减少(RR=2.33,95%CI:1.62～3.35,P<0.01)、3～4级中性粒细胞减少(RR=3.09,95%CI:1.72～5.53,P=0.000 1)、3～4级血小板减少(RR=2.96,95%CI:1.58～5.54,P=0.000 07)和3～4级恶心呕吐(RR=4.89,95%CI:2.46～9.72,P<0.01)等不良反应,差异均有统计学意义。结论:与非铂单药方案相比,含铂双药方案可提高化疗有效率,但不能改善1年生存率,且含铂双药组发生3～4级不良反应的可能性更大,故不适合作为老年晚期NSCLC一线化疗方案,但这一结论仍需开展针对老年晚期NSCLC患者的大样本随机对照试验加以验证。     

High dose chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis

BACKGROUND: High dose chemotherapy with autologous transplantation of bone marrow or peripheral stem cells (autograft) has been considered promising for treating poor prognosis breast cancer. We reviewed the relevant evidence. METHODS: We included randomised controlled trials comparing high dose chemotherapy and autograft with conventional chemotherapy for women with early poor prognosis breast cancer. We searched medical databases (Cochrane Library, MEDLINE, EMBASE), websites (co-operative cancer research groups, American Society of Clinical Oncologists) and citations of articles found, to September 2006. Where appropriate, data were pooled to obtain a relative risk, using a fixed effects model. Clinical, methodological and statistical heterogeneity were examined with sensitivity analyses. FINDINGS: Thirteen trials with 5064 women were included. There was a significant benefit in event-free survival for the high dose group at three years (RR 1.19 (95% CI 1.06, 1.19)) and four years (RR 1.24 (95% CI 1.03, 1.50)) and at five years this benefit approached statistical significance (RR 1.06 (95% CI 1.00, 1.13)). Overall survival rates were not significantly different at any stage of follow up. There were significantly more treatment-related deaths on the high dose arm (RR 8.58 (95% CI 4.13, 17.80)). Morbidity was higher in the high dose group but there was no significant difference in the incidence of second cancers. The high dose group reported significantly worse quality of life immediately after treatment, but there were few differences by one year. INTERPRETATION: There is insufficient evidence supporting routine use of high dose chemotherapy with autograft for treating early poor prognosis breast cancer.     

Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis

This systematic review and meta-analysis is the first to evaluate the evidence for an association between metformin use and cancer outcomes in patients undergoing treatment with curative intent for individual cancer types. Our findings suggest that adjuvant metformin could have beneficial effects, particularly on cancer outcomes in colorectal and prostate cancer. Randomised trials are warranted.BackgroundMetformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented.Patients and methodsWe systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer. Studies were assessed for design and quality, and a meta-analysis was conducted to quantify the adjuvant effect of metformin on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS), to inform future trial design.ResultsOf 7670 articles screened, 27 eligible studies were identified comprising 24 178 participants, all enrolled in observational studies. In those with early-stage colorectal cancer, metformin use was associated with a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47–0.85; OS HR 0.69, CI 0.58–0.83; CSS HR 0.58, CI 0.39–0.86]. For men with early-stage prostate cancer, metformin was associated with significant, or borderline significant, benefits in all outcomes (RFS HR 0.83, CI 0.69–1.00; OS HR 0.82, CI 0.73–0.93; CSS HR 0.58, CI 0.37–0.93); however, there was significant heterogeneity between studies. The data suggest that prostate cancer patients treated with radical radiotherapy may benefit more from metformin (RFS HR 0.45, CI 0.29–0.70). In breast and urothelial cancer, no significant benefits were identified. Sufficient data were not available to conduct analyses on the impact of metformin dose and duration.ConclusionsOur findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical radiotherapy, and randomised, controlled trials which investigate dose and duration, alongside efficacy, are advocated.