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Gynecologic Oncology Dec 2019More than 80 % of women with advanced ovarian cancer relapse either during or after adjuvant therapy. Platinum-sensitive women are rechallenged with a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
More than 80 % of women with advanced ovarian cancer relapse either during or after adjuvant therapy. Platinum-sensitive women are rechallenged with a platinum-combination therapy and platinum-resistant women are challenged with non-platinum drugs. Gemcitabine is one of many treatments that can be used both as single-agent or as combination therapy for the treatment of recurrent ovarian cancer.
METHODS
We included all randomised controlled trials investigating patients treated with gemcitabine for recurrent ovarian cancer and reporting data on overall survival, progression-free survival and toxicity. CENTRAL, EMBASE and MEDLINE were searched on the 31 of May 2019.
RESULTS
We included six randomised controlled trials that evaluated gemcitabine either alone or as combination therapy. Two studies compared gemcitabine to pegylated liposomal doxorubicin in women with platinum-resistant recurrent ovarian cancer. Difference in overall and progression-free survival was non-significant. Gemcitabine treatment was associated with significantly more neutropenia, whereas pegylated liposomal doxorubicin was associated with significantly more hand-foot syndrome. One study evaluated carboplatin and gemcitabine to carboplatin. Difference in overall survival was non-significant, but progression-free survival was longer with gemcitabine and carboplatin (HR: 0.72, 95% CI 0.58-0.9). One study evaluated gemcitabine with gemcitabine and pertuzumab. Overall survival and progression-free survival was similar between the two arms. One study compared gemcitabine and carboplatin to gemcitabine, carboplatin and bevacizumab. Overall survival was similar in the two arms. Progression-free survival was significantly better in the bevacizumab arm (HR 0.48 95% CI 0.39-0.61). One study compared etoposide and gemcitabine to etoposide. The study showed similar overall survival and progression-free survival.
DISCUSSION
The results show that gemcitabine is an active and safe agent in the treatment of both platinum-sensitive and resistant recurrent ovarian cancer but might highlight the need of new randomised studies in heavily pre-treated patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Gemcitabine
PubMed: 31604664
DOI: 10.1016/j.ygyno.2019.09.026 -
Medicine Sep 2019This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with...
BACKGROUND
This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with HER2-positive breast cancer (HER2-PBC).
METHODS
A comprehensive literature search for this study will consist of 2 parts: electronic database records and gray literature. The electronic database literatures are searched from PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be searched from inception up to the present. In addition, gray literatures, such as dissertations, ongoing trials, and so on, will also be searched. Two authors will independently read the records, extract data collection, and evaluate the risk of bias. RevMan V.5.3 software will be applied for statistical analysis.
RESULTS
This study will summarize up-to-date evidence of PTD for patients with HER2-PBC via overall survival, complete response, cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities.
CONCLUSION
This study will provide efficacy and safety of PTD for HER2-PBC.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Female; Genes, erbB-2; Humans; Receptor, ErbB-2; Trastuzumab; Treatment Outcome
PubMed: 31568001
DOI: 10.1097/MD.0000000000017262 -
Breast Cancer (Tokyo, Japan) Mar 2020We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify...
PURPOSE
We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2 metastatic breast cancer (MBC).
METHODS
Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2 MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS).
RESULTS
A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes.
CONCLUSIONS
These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2 MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2 MBC.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Female; Humans; Molecular Targeted Therapy; Network Meta-Analysis; Receptor, ErbB-2; Survival Rate; Taxoids; Trastuzumab; Treatment Outcome
PubMed: 31529262
DOI: 10.1007/s12282-019-01007-9 -
The Lancet. Oncology Mar 2019Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated... (Meta-Analysis)
Meta-Analysis
Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.
BACKGROUND
Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated this surrogacy in the adjuvant setting of treatment with anti-HER2 antibodies.
METHODS
In a systematic review and meta-analysis, we identified published and non-published randomised controlled trials with completed accrual and available disease-free survival and overall survival results for the intention-to-treat population as of September 2016. Bibliographic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials), clinical trial registries (Clinicaltrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and PharmNet.Bund), and trial registries from relevant pharmaceutical companies were searched. Eligibility for treatment of HER2-positive early breast cancer required at least one group to have an anti-HER antibody treatment (ie, trastuzumab, pertuzumab, or trastuzumab emtansine) planned for 12 months, and at least one control arm with chemotherapy without the antibody, a lower total dose or duration of the antibody, or observation alone. Units of analysis were contrasts: two-group trials gave rise to one contrast, whereas trials with more than two groups gave rise to more than one contrast. We excluded trials enrolling patients with recurrent, metastatic, or non-invasive disease, and those testing neoadjuvant therapy exclusively. Our primary objective was to estimate patient-level and trial-level correlations between disease-free survival and overall survival. We measured the association between disease-free survival and overall survival using Spearman's correlation coefficient (r), and the association between hazard ratios (HRs) for disease-free survival and overall survival using R. We computed the surrogate threshold effect, the maximum HR for disease-free survival that statistically predicts an HR for overall survival less than 1·00 in a future trial.
FINDINGS
Eight trials (n=21 480 patients) gave rise to a full set (12 contrasts). Patient-level associations between disease-free and overall survival were strong (r=0·90 [95% CI 0·89-0·90]). Trial-level associations gave rise to values of R of 0·75 (95% CI 0·50-1·00) for the full set. Subgroups defined by nodal status and hormone receptor status yielded qualitatively similar results. Depending on the expected number of deaths in a future trial, the surrogate threshold effects ranged from 0·56 to 0·81, based on the full set.
INTERPRETATION
These findings suggest that it is appropriate to continue to use disease-free survival as a surrogate for overall survival in trials in HER-2-positive, early breast cancer. The key limitation of this study is the dependence of its results on the trials included and on the existence of an outlying trial.
FUNDING
Roche Pharma AG.
Topics: Ado-Trastuzumab Emtansine; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Neoplasm Staging; Proportional Hazards Models; Receptor, ErbB-2; Treatment Outcome
PubMed: 30709633
DOI: 10.1016/S1470-2045(18)30750-2 -
OncoTargets and Therapy 2019To evaluate efficacy and safety of lapatinib or trastuzumab alone or both plus chemotherapy for the treatment of breast cancer patients with positive HER-2 expression.
AIM
To evaluate efficacy and safety of lapatinib or trastuzumab alone or both plus chemotherapy for the treatment of breast cancer patients with positive HER-2 expression.
METHODS
Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, OVID, Embase, Chinese Biomedical Literature Database, and China Academic Journals Database were searched from 1994 through December 2017 using the keywords "breast cancer", "preoperative", "neo-adjuvant", "lapatinib", "pertuzumab", "Herceptin", and "trastuzumab".
RESULTS
Meta-analysis found that pathological complete response (PCR; risk ratio [RR]=0.82, 95% CI: 0.72-0.93) and tall PCR (tPCR; RR=0.77, 95% CI: 0.67-0.88) of chemotherapy plus lapatinib were significantly less effective or safe compared to that of chemotherapy plus trastuzumab (<0.05). PCR (RR=1.30, 95% CI: 1.15-1.47) and tPCR (RR=1.32, 95% CI: 1.16-1.50) of chemotherapy plus both lapatinib and trastuzumab were significantly superior to that of chemotherapy plus trastuzumab alone (<0.05). However, there was no significant difference in breast reservation rate between chemotherapy plus lapatinib vs chemotherapy plus trastuzumab (RR=0.91, 95% CI: 0.72-1.16) or chemotherapy plus both lapatinib and trastuzumab (RR=1.11, 95% CI: 0.73-1.68, >0.05). Incidence of diarrhea, hepatic toxicity, and skin rash in the groups of chemotherapy plus lapatinib or chemotherapy plus both lapatinib and trastuzumab was significantly higher than that in chemotherapy plus trastuzumab (<0.05).
CONCLUSION
Efficacy of lapatinib was less than that of trastuzumab, but incidence of adverse effect of lapatinib was higher than that of trastuzumab. Combination of chemotherapy plus both lapatinib and trastuzumab could significantly increase PCR and tPCR in breast cancer patients, but rate of breast conservation, event-free survival, and overall survival was not significantly improved. Incidence of diarrhea, hepatic toxicity, and skin rash was significantly increased in the groups using lapatinib.
PubMed: 30655674
DOI: 10.2147/OTT.S183304 -
The Cochrane Database of Systematic... Oct 2018This is an update of a previously published version of the review (Issue 10, 2011).Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an update of a previously published version of the review (Issue 10, 2011).Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among women worldwide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy. Between 55% and 75% of women who respond to first-line therapy experience relapse within two years. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Improved understanding about the molecular basis of EOC has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and anti-EGFR antibodies.
OBJECTIVES
To compare the effectiveness and harmful effects of interventions that target the epidermal growth factor receptor in the treatment of epithelial ovarian cancer (EOC).
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2010, Issue 4), MEDLINE, and Embase up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field. This update includes further searches up to September 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven EOC.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data, assessed risk of bias, and performed GRADE assessment.
MAIN RESULTS
From 6105 references obtained through the literature search and an additional 15 references derived from grey literature searches, we identified seven RCTs that met our inclusion criteria and included 1725 participants. Trial results show that after first-line chemotherapy is provided, maintenance treatment with erlotinib (EGFR tyrosine kinase inhibitor (TKI)) probably makes little or no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.81 to 1.20; one study; 835 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 1.05, 95% CI 0.90 to 1.23; one study; 835 participants; very low-certainty evidence). Less than 50% of participants provided quality of life data, and study authors reported these results incompletely. The certainty of evidence is very low, but treatment may reduce quality of life compared to observation.Treatment with an EGFR TKI (vandetanib) for women with relapsed EOC may make little or no difference in overall survival (HR 1.25, 95% CI 0.80 to 1.95; one study; 129 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 0.99, 95% CI 0.69 to 1.42; one study; 129 participants; very low-certainty evidence). In treating patients with relapse, giving EGFR TKI may slightly increase some toxicities, such as severe rash (risk ratio (RR) 13.63, 95% CI 0.78 to 236.87; one study; 125 participants; very low-certainty evidence). Quality of life data were not available for meta-analysis.Anti-EGFR antibody treatment in relapsed EOC may or may not make a difference to overall survival (HR 0.93, 95% CI 0.74 to 1.18; four studies; 658 participants; moderate-certainty evidence) and may or may not have any effect on progression-free survival (HR 0.90, 95% CI 0.70 to 1.16; four studies; 658 participants; low-certainty evidence). Anti-EGFR antibody treatment may or may not increase side effects, including severe nausea and/or vomiting (RR 1.27, 95% CI 0.56 to 2.89; three studies; 503 participants; low-certainty evidence), severe fatigue (RR 1.06, 95% CI 0.66 to 1.73; I² = 0%; four studies; 652 participants; low-certainty evidence), and hypokalaemia (RR 2.01, 95% CI 0.80 to 5.06; I² = 0%; three studies; 522 participants; low-certainty evidence). Severe diarrhoea rates were heterogeneous across studies (RR 2.87, 95% CI 0.59 to 13.89; four studies; 652 participants; low-certainty evidence), and subgroup analysis revealed that severe diarrhoea was more likely with pertuzumab (RR 6.37, 95% CI 1.89 to 21.45; I² = 0%; three studies; 432 participants; low-certainty evidence) than with seribantumab treatment (RR 0.38, 95% CI 0.07 to 2.23; I² = 0%; one study; 220 participants; very low-certainty evidence). Quality of life data were incompletely reported, and we were unable to combine them in a meta-analysis.
AUTHORS' CONCLUSIONS
Current evidence suggests that an anti-EGFR single-agent biological treatment (EGFR TKI or anti-EGFR antibody) makes little or no difference to survival, either as maintenance treatment after first-line chemotherapy or in association with chemotherapy in recurrent cancer. Anti-EGFR therapy may increase some side effects and may or may not reduce quality of life.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Deoxycytidine; ErbB Receptors; Erlotinib Hydrochloride; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Piperidines; Progression-Free Survival; Quality of Life; Quinazolines; Randomized Controlled Trials as Topic
PubMed: 30321910
DOI: 10.1002/14651858.CD007927.pub4 -
Journal of Clinical Oncology : Official... Sep 2018Purpose To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor...
Purpose To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab emtansine for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone. Additional information is available at www.asco.org/breast-cancer-guidelines .
Topics: Antineoplastic Agents; Breast Neoplasms; Female; Humans; Receptor, ErbB-2
PubMed: 29939838
DOI: 10.1200/JCO.2018.79.2697 -
European Journal of Cancer (Oxford,... Jan 2018The cost of cancer drugs continues to escalate with the rapid development and approval of novel therapies, especially over the course of the last decade. In human... (Review)
Review
The cost of cancer drugs continues to escalate with the rapid development and approval of novel therapies, especially over the course of the last decade. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the survival benefits gained by new treatments have been undeniably substantial. It is important to assess the financial value of these therapies for decision making at both the societal and individual level. This information is key for managing resources in resource-limited health care systems, while at the same time supporting patient decision-making and conversations between patient and physicians on cost versus benefit. In this article, we perform a systematic review of cost-effectiveness analyses that have been completed to date on HER2-targeted agents, focussing on those that correlate with standard of care therapy. Our discussion also highlights potential strategies to overcome several limitations associated with measuring value for anticancer drugs.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; Cost-Benefit Analysis; Female; Humans; Lapatinib; Quinazolines; Receptor, ErbB-2; Trastuzumab
PubMed: 29241083
DOI: 10.1016/j.ejca.2017.10.037 -
Radiotherapy and Oncology : Journal of... Aug 2017Over the past few years, anti-HER2 targeted therapies have proven to be a key treatment in the management of human epidermal growth receptor 2 (HER2)-positive breast... (Review)
Review
BACKGROUND
Over the past few years, anti-HER2 targeted therapies have proven to be a key treatment in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers, as well as gastrointestinal tract tumors and head and neck tumors. Anti-HER2 therapies administered alone or in combination with chemotherapy have been extensively studied, but only limited robust data are available concerning the safety and efficacy of anti-HER2 molecules in combination with radiotherapy.
METHODS
We searched on Medline, Embase and Cochrane databases the articles providing data on the concomitant association between the antiHER2 therapies used in clinical practice (trastuzumab, pertuzumab, lapatinib and T-DM1) with radiotherapy. The articles were selected according to their pre-clinical and clinical relevance.
RESULTS
The trastuzumab-irradiation combination is the most studied, with a focus on the cardiac toxicity. The combination of lapatinib-irradiation was particularly studied in the context of cerebral metastases of HER2-positive breast cancer. The data on pertuzumab and T-DM1 were poor and are mainly case reports.
CONCLUSION
To date, reliable conclusions about the toxicity and/or efficacy of concomitant irradiation with anti-HER2 therapies are difficult to make due to the heterogeneity of the data in the literature and need to be confirmed on a larger scale and long term follow-up. Nevertheless, no serious adverse events are reported and the toxicity profile seems to be manageable.
Topics: Breast Neoplasms; Chemoradiotherapy; Female; Humans; Molecular Targeted Therapy; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptor, ErbB-2
PubMed: 28751231
DOI: 10.1016/j.radonc.2017.07.006 -
International Journal of Clinical... Sep 2017Pertuzumab, as an adjunctive therapy to trastuzumab and docetaxel, has been reported to be potentially beneficial for the treatment of human epidermal growth factor... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pertuzumab, as an adjunctive therapy to trastuzumab and docetaxel, has been reported to be potentially beneficial for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pertuzumab supplementation in patients with HER2-positive metastatic breast cancer.
METHODS
Medline, SCOPUS, Google Scholar, Cochrane library databases, EMBASE, Springer, and Science Direct were systematically searched. Randomized controlled trials (RCTs) assessing the effect of pertuzumab + trastuzumab + docetaxel vs. trastuzumab + docetaxel on the treatment of HER2-positive metastatic breast cancer were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were death, overall survival, and progression-free survival. Meta-analysis was performed using fixed- or random-effect model.
RESULTS
Five RCTs involving 3,742 patients were included in the meta-analysis. Overall, compared with placebo and trastuzumab + docetaxel treatment, combination treatment of pertuzumab + trastuzumab + docetaxel treatment was associated with the significantly reduced death (hazard ratio (HR) = 0.67; 95% confidence interval (CI) = 0.57 - 0.78; p < 0.005) as well as improved overall survival (HR = 0.66; 95% CI = 0.35 - 0.67; p = 0.98) and progression-free survival (HR = 0.64; 95% CI = 0.58 - 0.71; p < 0.005). Moreover, pertuzumab supplementation did not increase the number of patients with reductions in the left ventricular ejection fraction (LVEF) of 10% or more (risk ratio (RR) = 0.70; 95% CI = 0.47 - 1.04; p = 0.07).
CONCLUSION
Pertuzumab + trastuzumab + docetaxel treatment significantly reduced death, increased overall survival, and progression-free survival in patients with HER2-positive metastatic breast cancer compared to placebo and trastuzumab + docetaxel treatment, but showed no increased adverse events. .
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Docetaxel; Female; Humans; Middle Aged; Proportional Hazards Models; Receptor, ErbB-2; Taxoids; Trastuzumab; Young Adult
PubMed: 28737130
DOI: 10.5414/CP202921