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Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.
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Vernal keratoconjunctivitis (VKC) is a chronic, progressive, allergic ocular surface disorder that can lead to sight-threatening complications. VKC occurs primarily in children and generally resolves about the time of puberty; however, case series and retrospective analyses indicate that approximately 10% of patients with VKC are adults, and that a subset of adult cases develop after puberty. Consequently, two age-related variants of VKC have recently been described: early-onset VKC-which manifests during childhood and persists into adult life-and late-onset disease, which emerges de novo after puberty. Although the signs and symptoms of adult and childhood VKC are similar, adult VKC is a long-lasting disease characterized by severe inflammation and increased risk of conjunctival fibrosis, which may place adult patients at higher risk for sight-threatening complications and adverse impacts on daily life. This review discusses the epidemiology, signs, symptoms, immunopathogenesis of adult VKC variants, and highlights current gaps in research and management of patients with this condition.
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PURPOSE: To investigate whether neurotrophic keratopathy is present in limbal stem cell deficiency (LSCD), by measuring corneal sensation and characterizing corneal subbasal nerve plexus. DESIGN: Prospective, cross-sectional, case-control comparative study. METHODS: A total of 46 eyes with LSCD and 14 normal eyes were recruited from 2019 to 2022. Corneal sensation was measured using a Cochet-Bonnet esthesiometer, and subbasal nerve plexus was imaged using in vivo confocal microscopy (IVCM) at the central cornea and 4 limbal regions. Subbasal nerve density (SND, number of nerves/mm2), subbasal nerve length (SNL, total length of nerves/mm2) and subbasal nerve branch density (SNBD, number of branches/mm2) were quantified. LSCD was graded to stage 1, 2, and 3 using a previously established staging method consisting of clinical scores, basal cell density, central corneal epithelial thickness, and SNL. RESULTS: The mean (±SD) cornea sensation in the central cornea and limbus were 29.2 ± 21.5 and 33.6 ± 15.1 mm in the LSCD group and 57.6 ± 5.8 and 54.3 ± 4.7 mm in the control group, respectively (all P < .001). In sectoral LSCD, the corneal sensation in the affected regions (29.1 ± 17.6 mm) decreased significantly compared to the unaffected regions (41.4 ± 18.2 mm, P < .001). Central corneal SND, SNL, and SNBD were reduced by 84.6%, 82.6%, and 89.2%, respectively, in LSCD compared to controls (all P < 0.05). The central corneal sensation negatively correlated with the severity of LSCD (rho = -0.64, P < .0001) and positively correlated with SND, SNL, and SNBD (rho = 0.63, 0.66, and 0.56, respectively; all P < .001). CONCLUSIONS: Corneal sensation was reduced in eyes with LSCD. The degree of corneal sensation reduction positively correlated with the severity of LSCD. This finding demonstrated the coexistence of neurotropic keratopathy in LSCD.
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PURPOSE: To assess the utility of 3D, tablet-based, glasses-free Accurate STEReotest (ASTEROID) in children compared with the Titmus test. METHODS: Children aged 5-13 years were enrolled in a single-center, nonrandomized, observational comparison study and analyzed by age (5-7 vs 8-13 years) and visual acuity (20/25 or better in both eyes vs abnormal). Each participant underwent both the ASTEROID and Titmus stereoacuity tests. Stereoacuity was defined as fine (≤60 arcsec), moderate (61-200 arcsec), coarse (201-1199 arcsec), or very coarse to nil (≥1200 arcsec). Agreement between the tests was assessed using a weighted kappa (κ) statistic based on all four categories. RESULTS: A total of 112 children were included: 28 aged 5-7 with normal visual acuity, 30 aged 5-7 with abnormal visual acuity, 34 aged 8-13 with normal visual acuity, and 20 aged 8-13 with abnormal visual acuity. Mean ASTEROID score was 688 ± 533 arcsec (range, 13-1200 arcsec). Agreement between ASTEROID and Titmus test scores for participants overall was moderate (κ = 0.52). By subgroup, agreement was fair for children 5-7 with abnormal visual acuity (κ = 0.31), moderate for children 5-7 with normal visual acuity (κ = 0.47) and children 8-13 with normal visual acuity (κ = 0.42), and substantial for children 8-13 with abnormal visual acuity (κ = 0.76). Where ASTEROID and Titmus score group varied, ASTEROID score was poorer in 94% (47/50) of cases. CONCLUSIONS: ASTEROID is a digital, tablet-based test that evaluates global stereopsis, does not require glasses, and provides a continuum of scores. Among children, ASTEROID has good agreement with the Titmus test; however, it may be more sensitive at detecting stereovision deficits. Further study is necessary to determine which test is more accurate.
Subject(s)
Computers, Handheld , Depth Perception , Vision Tests , Visual Acuity , Humans , Child , Visual Acuity/physiology , Vision Tests/methods , Child, Preschool , Adolescent , Female , Male , Depth Perception/physiology , Vision Disorders/physiopathology , Vision Disorders/diagnosis , Reproducibility of Results , Imaging, Three-DimensionalABSTRACT
Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor2-negative breast cancer (HR+/HER2- BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2- BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Immunoconjugates , Lung Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Immunoconjugates/adverse effects , Trastuzumab , Receptor, ErbB-2 , Camptothecin , Clinical Trials, Phase I as TopicABSTRACT
PURPOSE: Our purpose was to evaluate the clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing stereotactic body radiation therapy (SBRT) for central non-small cell lung cancer (NSCLC) tumors. METHODS AND MATERIALS: A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located thoracic tumors from February 2007 to December 2021 was performed. The SAN and AVN were contoured in accordance with a published contouring atlas, and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and overall survival. RESULTS: Among 93 eligible patients, the median age was 72.5 years (IQR, 66.6-78.3), and median follow-up was 32.4 months (IQR, 13.0-49.6). The median SAN Dmax and Dmean were 95 cGy (range, 9-5394) and 58 cGy (range, 7-3168), respectively. The median AVN Dmax and Dmean were 45 cGy (range, 4-2121) and 34 cGy (range, 3-1667), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1309 and 836 cGy, respectively. No associations between AVN parameters and survival outcomes were identified. Upon multivariate Cox regression, the SAN Dmax cutoff (hazard ratio [HR], 2.03 [1.09-3.79]; P = .026) and SAN Dmean cutoff (HR, 2.22 [1.20-4.12]; P = .011) were significantly associated with overall survival. For noncancer-associated survival, the SAN Dmax cutoff trended toward significance (HR, 2.02 [0.89-4.57]; P = .092), and the SAN Dmean cutoff remained significantly associated (HR, 2.34 [1.05-5.18]; P = .037). CONCLUSIONS: For patients undergoing SBRT for NSCLC, SAN Dmax and Dmean were significantly associated with worse overall survival using cut-off values of 1309 and 836 cGy, respectively. Further studies examining the effect of SAN irradiation during SBRT are warranted.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Humans , Aged , Carcinoma, Non-Small-Cell Lung/surgery , Radiosurgery/methods , Sinoatrial Node , Radiotherapy DosageABSTRACT
PURPOSE: To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020. METHODS: Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development. MAIN OUTCOME MEASURES: The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated. RESULTS: Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53-0.65), 0.74 (95% CI, 0.68-0.81), and 1.99 (95% CI, 1.88-2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28-7.36] to 11.80 [95% CI, 10.40-13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57-3.75; 95% CI, 2.17-4.34), male sex (OR, 1.38; 95% CI, 1.26-1.50), Asian descent (OR, 3.12; 95% CI, 2.70-3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02-1.55) were associated with POSID development. CONCLUSIONS: This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Importance: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. Objective: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. Design, Setting, and Participants: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. Results: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was "pediatric blepharokeratoconjunctivitis," and the agreed-on definition was "Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring." The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. Conclusions and Relevance: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel's clinical experience, requiring further validation with real patient data analysis.
Subject(s)
Blepharitis , Keratoconjunctivitis , Adolescent , Child , Humans , Keratoconjunctivitis/diagnosis , Keratoconjunctivitis/complications , Keratoconjunctivitis/drug therapy , Blepharitis/diagnosis , Blepharitis/drug therapy , Eyelids , Conjunctiva , Cornea , Chronic DiseaseABSTRACT
Introduction: This study aims to report our 13-year institutional experience with single-fraction stereotactic body radiation therapy (SF-SBRT) for early stage NSCLC. Methods: A single-institutional retrospective review of patients with biopsy-proven peripheral cT1-2N0M0 NSCLC undergoing definitive SF-SBRT between September 2008 and May 2022 was performed. All patients were treated to 27 Gy with heterogeneity corrections or 30 Gy without. Primary outcomes were overall survival and progression-free survival. Secondary outcomes included local failure, nodal failure, distant failure, and second primary lung cancer. Results: Among 263 eligible patients, the median age was 76 years (interquartile range [IQR]: 70-81 y) and median follow-up time was 27.2 months (IQR: 14.25-44.9 mo). Median tumor size was 1.9 cm (IQR: 1.4-2.6 cm), and 224 (85%) tumors were T1. There were 92 patients (35%) alive at the time of analysis with a median follow-up of 34.0 months (IQR: 16.6-50.0 mo). Two- and five-year overall survival was 65% and 26%, respectively. A total of 74 patients (28%) developed disease progression. Rates of five-year local failure, nodal failure, distant failure, and second primary lung cancer were 12.7%, 14.7%, 23.5%, and 12.0%, respectively. Conclusions: Consistent with multiple prospective randomized trials, in a large real-world retrospective cohort, SF-SBRT for peripheral early stage NSCLC was an effective treatment approach.
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Durvalumab (Imfinzi®), a therapeutic human monoclonal antibody which binds to and blocks the activity of the immunosuppressive programmed death-ligand 1 (PD-L1) protein, is approved in the USA, EU, Japan and other countries in combination with gemcitabine and cisplatin for adults with advanced biliary tract cancer. In the pivotal phase 3 TOPAZ-1 trial, durvalumab plus gemcitabine and cisplatin significantly prolonged overall survival and progression-free survival compared with placebo plus gemcitabine and cisplatin in adults with advanced biliary tract cancer. Benefit from durvalumab was seen irrespective of primary tumour location, disease status at diagnosis (unresectable or recurrent), or initial levels of PD-L1 expression. The tolerability of durvalumab plus gemcitabine and cisplatin was manageable. Overall, the addition of durvalumab to gemcitabine and cisplatin is a valuable new treatment option for adults with advanced biliary tract cancer.
Biliary tract cancers are a diverse group of cancers that develop in the bile ducts or the gallbladder. Patients with these cancers typically have poor survival. Chemotherapy (gemcitabine plus cisplatin) has been the first-line treatment for biliary tract cancer for over a decade, with no new treatments further improving on its overall survival benefit until recently. Durvalumab (Imfinzi®) belongs to a class of drugs known as checkpoint inhibitors; these drugs activate the immune system to help fight cancer. In the phase 3 TOPAZ-1 trial, the addition of durvalumab to first-line chemotherapy prolonged the overall survival compared with placebo plus chemotherapy in adults with advanced biliary tract cancer. The tolerability of durvalumab in combination with chemotherapy was manageable. Thus, durvalumab plus gemcitabine and cisplatin is a valuable new treatment option for adults with advanced biliary tract cancer.
Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Adult , Humans , Deoxycytidine/therapeutic use , Biliary Tract Neoplasms/drug therapy , Biliary Tract Neoplasms/pathology , B7-H1 Antigen , Cisplatin/therapeutic use , Bile Duct Neoplasms/drug therapy , Gemcitabine , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment OutcomeABSTRACT
Baricitinib (Olumiant®), a Janus kinase (JAK) inhibitor, is the first drug approved for the treatment of severe alopecia areata in the USA and the EU. Severe alopecia areata is usually difficult to treat and relapse is common. Patients with this disorder are more likely to suffer from anxiety and depression. In two pivotal placebo-controlled phase 3 clinical trials in adults with severe alopecia areata, oral baricitinib once daily was associated with clinically meaningful scalp, eyebrow, and eyelash hair regrowth over 36 weeks. Baricitinib was generally well tolerated with the most common adverse events being infections, headaches, acne, and elevated levels of creatine phosphokinase. While longer-term data will be necessary to more fully understand the benefits and risks of the drug, currently available data suggest that baricitinib is a useful treatment for patients with severe alopecia areata.
Alopecia areata is a disorder in which an autoimmune attack is mounted against hair follicles, resulting in hair loss ranging from patches of hair loss through to complete hair loss. Alopecia areata can recur throughout an individual's lifetime and can cause significant psychological distress, with patients more likely to experience anxiety or depressive disorders within their lifetime. Baricitinib (Olumiant®) is a drug that blocks the signaling of immune messengers to halt autoimmune attack and allow hair regrowth. In two clinical trials, adults with severe alopecia areata receiving baricitinib were more likely to recover from an episode of alopecia areata (achieve 80% or more scalp coverage) than those receiving placebo. Eyebrow and eyelash regrowth was also more common in patients receiving baricitinib than placebo. Baricitinib was generally well tolerated, with infections being the most common adverse events. While longer-term data will be of interest, baricitinib appears to be a useful treatment for patients with severe alopecia areata.
Subject(s)
Alopecia Areata , Azetidines , Janus Kinase Inhibitors , Adult , Humans , Alopecia Areata/drug therapy , Azetidines/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Clinical Trials, Phase III as TopicABSTRACT
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.
Subject(s)
Cataract , Xanthomatosis, Cerebrotendinous , Child, Preschool , Humans , Child , Adolescent , Young Adult , Adult , Xanthomatosis, Cerebrotendinous/diagnosis , Xanthomatosis, Cerebrotendinous/epidemiology , Xanthomatosis, Cerebrotendinous/genetics , Prevalence , Cholestanol , Bile Acids and Salts , Cataract/diagnosis , Cataract/epidemiology , Cataract/geneticsABSTRACT
BACKGROUND: One of the core aims of the European Union of Medical Specialists is to harmonize training across Europe by creating European Training Requirements for all medical specialties including Ophthalmology. The theoretical part is already defined by the EBO, however as ophthalmology also includes surgical skills, we herein propose a surgical minimum curriculum for ophthalmology residents in Europe. METHODS: National and international ophthalmic training curricula which are publicly available in English were reviewed and compared. The final proposal was created from 5 criteria: 1. Disease prevalence; 2. Patient safety; 3. Case-trainee ratio; 4. Skill transfer; and 5. Technical difficulty. RESULTS: In total 7 different training curricula from across the world were compared. Among the surgical procedures, cataract surgery has the highest median number of procedures required to be completed during residency: 86 procedures (50-350). Followed by oculoplastics: 28 procedures (10-40) and panretinal photocoagulation: 27.5 procedures (10-49) Full procedural competence is proposed in 9 surgical skills, including YAG laser posterior capsulotomy, retinal argon laser, intravitreal injection, corneal foreign body removal, removal of corneal sutures, facial and periocular laceration repair, eyelid laceration repair, minor eyelid procedures, and punctal occlusion. These procedures are deemed essential and feasible for all ophthalmology residents in Europe to perform independently upon completion of their training. CONCLUSION: This proposal should be regarded as a recommendation based on comparable surgical curricula in use worldwide to establish standards across European countries and may serve as valuable insight to those responsible for compiling ETRs for ophthalmology, or their national curriculums.
Subject(s)
Cataract Extraction , Internship and Residency , Lacerations , Ophthalmology , Humans , Education, Medical, Graduate/methods , Curriculum , Ophthalmology/education , Cataract Extraction/education , Vitreous Body , Europe , Clinical CompetenceABSTRACT
Satralizumab (Enspryng®) is a monoclonal antibody that blocks the interleukin-6 (IL-6) receptor and is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in patients who are aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive. Patients with NMOSD are at risk of recurrent autoimmune attacks that primarily target the optic nerves and spinal cord but may also target other regions of the central nervous system; these attacks can lead to life-long disability. In the randomized, placebo-controlled phase III SAkuraSky and SAkuraStar trials, subcutaneous satralizumab as an add-on to immunosuppressive therapy or as a monotherapy, respectively, significantly reduced the risk of relapse compared with placebo in patients who were AQP4-IgG seropositive with NMOSD. Satralizumab was well tolerated; the most common adverse events were infection, headache, arthralgia, decreased white blood cell count, hyperlipidaemia and injection-related reactions. In the EU, satralizumab is the first IL-6 receptor blocker to be approved for treatment of AQP4-IgG-seropositive patients with NMOSD, has the potential advantage of subcutaneous administration, and is the only targeted treatment approved for adolescent patients with this disorder. Thus, satralizumab is a valuable treatment option for patients with NMOSD.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder, in which recurrent attacks by the body's own immune system can cause severe morbidity and disability. Immunoglobulin G antibodies targeting the aquaporin-4 (AQP4-IgG) water channel in cells of the central nervous system can be detected in the majority of patients with NMOSD. Satralizumab (Enspryng®), which is designed to suppress autoantibody production by blocking the interleukin-6 (IL-6) receptor, was found to significantly reduce the rate of immune attack recurrence compared with placebo when used as an add-on to standard immunosuppressive therapy (SAkuraSky trial) or when used alone (SAkuraStar trial). Satralizumab was well tolerated in the SAkuraSky and SAkuraStar trials, with infections (e.g. nasopharyngitis, upper respiratory tract infections) being the most common associated adverse event. In the EU, satralizumab is the first IL-6 receptor blocker approved for AQP4-IgG-seropositive patients with NMOSD and is the only subcutaneously administration targeted drug approved for NMOSD. Therefore, satralizumab represents a valuable treatment option for NMOSD.
Subject(s)
Neuromyelitis Optica , Adolescent , Humans , Neuromyelitis Optica/drug therapy , Autoantibodies/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Aquaporin 4/therapeutic use , Immunoglobulin GABSTRACT
Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.
In patients with hormone receptor positive (HR+) cancers, endocrine therapy is often used to reduce the risk of breast cancer recurrence after successful initial treatment; however, in a subset of patients, recurrence rates can remain high. In a pivotal phase III trial, the addition of abemaciclib [Verzenio® (USA) or Verzenios® (EU)] to standard endocrine therapy significantly reduced the rate of breast cancer recurrence compared with endocrine therapy alone in patients with HR+, human epidermal growth factor receptor 2 negative (HER2−), node-positive early breast cancer who were at a high risk of recurrence. Benefit was seen in both patients with characteristics that are associated with higher risk (premenopausal, high Ki-67 scores, previously received neoadjuvant chemotherapy) and comparatively lower risk of recurrence (postmenopausal, low Ki-67 scores). Diarrhoea, infections and neutropenia were the most common adverse events in patients receiving abemaciclib plus endocrine therapy. The overall tolerability of abemaciclib was acceptable. The addition of abemaciclib to endocrine therapy is a valuable therapeutic option for adjuvant therapy in high-risk patients with HR+, HER2−, node-positive early breast cancer.