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Cancer Treatment Reviews Apr 2022Adjuvant and neoadjuvant breast cancer treatments can reduce breast cancer mortality but may increase mortality from other causes. Information regarding treatment... (Review)
Review
BACKGROUND
Adjuvant and neoadjuvant breast cancer treatments can reduce breast cancer mortality but may increase mortality from other causes. Information regarding treatment benefits and risks is scattered widely through the literature. To inform clinical practice we collated and reviewed the highest quality evidence.
METHODS
Guidelines were searched to identify adjuvant or neoadjuvant treatment options recommended in early invasive breast cancer. For each option, systematic literature searches identified the highest-ranking evidence. For radiotherapy risks, searches for dose-response relationships and modern organ doses were also undertaken.
RESULTS
Treatment options recommended in the USA and elsewhere included chemotherapy (anthracycline, taxane, platinum, capecitabine), anti-human epidermal growth factor 2 therapy (trastuzumab, pertuzumab, trastuzumab emtansine, neratinib), endocrine therapy (tamoxifen, aromatase inhibitor, ovarian ablation/suppression) and bisphosphonates. Radiotherapy options were after breast conserving surgery (whole breast, partial breast, tumour bed boost, regional nodes) and after mastectomy (chest wall, regional nodes). Treatment options were supported by randomised evidence, including > 10,000 women for eight treatment comparisons, 1,000-10,000 for fifteen and < 1,000 for one. Most treatment comparisons reduced breast cancer mortality or recurrence by 10-25%, with no increase in non-breast-cancer death. Anthracycline chemotherapy and radiotherapy increased overall non-breast-cancer mortality. Anthracycline risk was from heart disease and leukaemia. Radiation-risks were mainly from heart disease, lung cancer and oesophageal cancer, and increased with increasing heart, lung and oesophagus radiation doses respectively. Taxanes increased leukaemia risk.
CONCLUSIONS
These benefits and risks inform treatment decisions for individuals and recommendations for groups of women.
Topics: Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Mastectomy; Neoadjuvant Therapy; Tamoxifen
PubMed: 35367784
DOI: 10.1016/j.ctrv.2022.102375 -
Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
Cancer Treatment Reviews Jul 2023Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of... (Review)
Review
BACKGROUND
Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of chemotherapy. Promising activity of novel ADCs, namely Trastuzumab Deruxtecan and Patritumab Deruxtecan, has been observed in hard-to treat molecular subtypes, such as HER2-positive and heavily pretreated EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). However, therapeutic advances are expected in certain subgroups of lung cancer patients, including non-oncogene-addicted NSCLC after failure of current standard of care (e.g., immunotherapy with or without chemotherapy, chemo-antiangiogenic treatment). Trophoblastic Cell Surface Antigen 2 (TROP-2) is a surface transmembrane glycoprotein member of the epithelial cell adhesion molecule (EpCAM) family. TROP-2 represents a promising therapeutic target in refractory non-oncogene-addicted NSCLC.
METHODOLOGY
We performed a systematic literature search of the clinical trials about TROP-2 directed ADCs in NSCLC referenced in the pubmed.gov database, Cochrane Library database and clinicaltrial.gov database.
RESULTS
First-in-humans ADCs targeting TROP-2, namely Sacituzumab Govitecan (SN-38) and Datopotamab Deruxtecan (Dxd), yielded promising activity signals in NSCLC with a manageable safety profile. Most common grade ≥ 3 adverse events (AEs) of Sacituzumab Govitecan included neutropenia (28 %), diarrhea (7 %), nausea (7 %), fatigue (6 %), and febrile neutropenia (4 %). Nausea and stomatitis were the most common all grade AEs with Datopotamab Deruxtecan; dyspnea, amylase increase, hyperglycemia and lymphopenia were reported as grade ≥ 3 AEs in less than 12 % of patients.
CONCLUSION
As more effective strategies are needed for patients with refractory non-oncogene-addicted NSCLC, the design of novel clinical trials with ADCs targeting TROP-2 is encouraged as both a monotherapy or combination strategy with existing agents (e.g., monoclonal antibodies targeting immune checkpoint inhibitors or chemotherapy).
Topics: Humans; Antineoplastic Agents; Camptothecin; Carcinoma, Non-Small-Cell Lung; Immunoconjugates; Irinotecan; Lung Neoplasms
PubMed: 37230055
DOI: 10.1016/j.ctrv.2023.102572 -
Journal of Clinical Oncology : Official... Aug 2022To update evidence-based guideline recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2...
PURPOSE
To update evidence-based guideline recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer.
METHODS
An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 545 articles. Outcomes of interest included efficacy and safety.
RESULTS
Of the 545 publications identified and reviewed, 14 were identified to form the evidentiary basis for the guideline 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 deruxtecan for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations. There is a lack of head-to-head trials; therefore, there is insufficient evidence to recommend one regimen over another. The patient and the clinician should discuss differences in treatment schedule, route, toxicities, etc during the decision-making process. Options include regimens with tucatinib, trastuzumab emtansine, trastuzumab deruxtecan (if either not previously administered), neratinib, lapatinib, chemotherapy, margetuximab, hormonal therapy, and abemaciclib plus trastuzumab plus fulvestrant, and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4-6 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 or 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 Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Practice Guidelines as Topic; Receptor, ErbB-2; Stroke Volume; Trastuzumab; Ventricular Function, Left
PubMed: 35640077
DOI: 10.1200/JCO.22.00519 -
Cancer Treatment Reviews Dec 2022Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic... (Review)
Review
Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).
Topics: Humans; Triple Negative Breast Neoplasms; Bevacizumab; Poly(ADP-ribose) Polymerase Inhibitors; Network Meta-Analysis; B7-H1 Antigen; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Paclitaxel; Algorithms
PubMed: 36202026
DOI: 10.1016/j.ctrv.2022.102468 -
Journal of Clinical Oncology : Official... Mar 2023To develop recommendations involving targeted therapies for patients with advanced gastroesophageal cancer.
PURPOSE
To develop recommendations involving targeted therapies for patients with advanced gastroesophageal cancer.
METHODS
The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.
RESULTS
Eighteen randomized controlled trials met the inclusion criteria for the systematic review.
RECOMMENDATIONS
For human epidermal growth factor receptor 2 (HER2)-negative patients with gastric adenocarcinoma (AC) and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 5, first-line therapy with nivolumab and chemotherapy (CT) is recommended. For HER2-negative patients with esophageal or gastroesophageal junction (GEJ) AC and PD-L1 CPS ≥ 5, first-line therapy with nivolumab and CT is recommended. First-line therapy with pembrolizumab and CT is recommended for HER2-negative patients with esophageal or GEJ AC and PD-L1 CPS ≥ 10. For patients with esophageal squamous cell carcinoma and PD-L1 tumor proportion score ≥ 1%, nivolumab plus CT, or nivolumab plus ipilimumab is recommended; for patients with esophageal squamous cell carcinoma and PD-L1 CPS ≥ 10, pembrolizumab plus CT is recommended. For patients with HER2-positive gastric or GEJ previously untreated, unresectable or metastatic AC, trastuzumab plus pembrolizumab is recommended, in combination with CT. For patients with advanced gastroesophageal or GEJ AC whose disease has progressed after first-line therapy, ramucirumab plus paclitaxel is recommended. For HER2-positive patients with gastric or GEJ AC who have progressed after first-line therapy, trastuzumab deruxtecan is recommended. In all cases, participation in a clinical trial is recommended as it is the panel's expectation that targeted treatment options for gastroesophageal cancer will continue to evolve.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
Topics: Humans; Esophageal Neoplasms; Nivolumab; B7-H1 Antigen; Esophageal Squamous Cell Carcinoma; Stomach Neoplasms; Esophagogastric Junction; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36603169
DOI: 10.1200/JCO.22.02331 -
Journal of Clinical Oncology : Official... Aug 2023To update ASCO-College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware...
PURPOSE
To update ASCO-College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ADCs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
METHODS
An Update Panel conducted a systematic literature review to identify signals for updating recommendations.
RESULTS
The search identified 173 abstracts. Of five potential publications reviewed, none constituted a signal for revising existing recommendations.
RECOMMENDATIONS
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
DISCUSSION
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences.Additional information is available at www.asco.org/breast-cancer-guidelines.
Topics: Humans; Female; Breast Neoplasms; In Situ Hybridization, Fluorescence; Pathologists; Receptor, ErbB-2; Biomarkers, Tumor
PubMed: 37284804
DOI: 10.1200/JCO.22.02864 -
ESMO Open Aug 2023Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd.
MATERIALS AND METHODS
We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software.
RESULTS
We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%).
CONCLUSIONS
In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Cardiotoxicity; Incidence; Stroke Volume; Ventricular Function, Left; Lung Diseases, Interstitial
PubMed: 37481956
DOI: 10.1016/j.esmoop.2023.101613 -
Drugs Jun 2022Trastuzumab deruxtecan (T-DXd) is a novel anti-ERBB2 antibody drug conjugate that appears to be associated with an increased risk of lung toxicity. We performed a...
BACKGROUND AND OBJECTIVE
Trastuzumab deruxtecan (T-DXd) is a novel anti-ERBB2 antibody drug conjugate that appears to be associated with an increased risk of lung toxicity. We performed a systematic review to describe the incidence, severity, and management of T-DXd-induced interstitial lung disease (ILD) or pneumonitis.
METHODS
We searched PubMed/MEDLINE, Embase, Cochrane, and Web of Sciences through to 1 January, 2022, for human clinical trials that assessed T-DXd in adults with ERBB2-positive advanced solid tumors and described the rate of ILD/pneumonitis. Study screening was performed by two researchers. Data were extracted from the full-text articles.
RESULTS
Fourteen studies with a total of 1193 patients with different types of advanced solid malignancies were included in our systematic review. The overall incidence of all-grade ILD/pneumonitis cases that were adjudicated by an independent committee was 11.40% (ILD/pneumonitis cases, n = 136 out of total n = 1193). Grading of the adjudicated T-DXd-induced ILD/pneumonitis was reported in 122 patients with the majority of the cases (78.69%, n = 96) occurring as grade 1 or 2. Death was reported in 13 out of 122 (10.66%) patients. The highest incidence of ILD/pneumonitis was seen in patients with uterine carcinomatosis (26.47%) and non-small cell lung cancer (24.77%). Interstitial lung disease/pneumonitis events were treated with a dose interruption or reduction, treatment discontinuation, corticosteroids, and supportive care.
CONCLUSIONS
Interstitial lung disease/pneumonitis is a well-described, serious, and potentially life-threatening adverse event that is associated with T-DXd. Further studies are needed to identify the risk factors and the underlying pathophysiology of T-DXd-induced ILD/pneumonitis to prevent occurrence and to develop effective management strategies.
Topics: Adult; Camptothecin; Carcinoma, Non-Small-Cell Lung; Humans; Immunoconjugates; Lung Diseases, Interstitial; Lung Neoplasms; Pneumonia; Receptor, ErbB-2; Trastuzumab
PubMed: 35759121
DOI: 10.1007/s40265-022-01736-w -
Archives of Pathology & Laboratory... Sep 2023To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2)...
PURPOSE.—
To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
METHODS.—
The Update Panel conducted a systematic literature review to identify signals for updating recommendations.
RESULTS.—
The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations.
RECOMMENDATIONS.—
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
DISCUSSION.—
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.
Topics: Humans; Female; Breast Neoplasms; In Situ Hybridization, Fluorescence; Receptor, ErbB-2; In Situ Hybridization; Biomarkers, Tumor
PubMed: 37303228
DOI: 10.5858/arpa.2023-0950-SA