Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice.

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-ß-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.

Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. RESULTS: Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. CONCLUSIONS: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

Oral Psoriasis Therapies.

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.

Anti-inflammatory effects of elexacaftor/tezacaftor/ivacaftor in adults with cystic fibrosis heterozygous for F508del.

Inflammation is a key driver in the pathogenesis of cystic fibrosis (CF). We assessed the effectiveness of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on downregulating systemic and immune cell-derived inflammatory cytokines. We also monitored the impact of ETI therapy on clinical outcome. Adults with CF, heterozygous for F508del (n = 19), were assessed at baseline, one month and three months following ETI therapy, and clinical outcomes were measured, including sweat chloride, lung function, weight, neutrophil count and C-reactive protein (CRP). Cytokine quantifications were measured in serum and following stimulation of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS) and adenosine triphosphate and analysed using LEGEND plex™ Human Inflammation Panel 1 by flow cytometry (n = 19). ASC specks were measured in serum and caspase-1 activity and mRNA levels determined from stimulated PBMCs were determined. Patients remained stable over the study period. ETI therapy resulted in decreased sweat chloride concentrations (p < 0.0001), CRP (p = 0.0112) and neutrophil count (p = 0.0216) and increased percent predicted forced expiratory volume (ppFEV1) (p = 0.0399) from baseline to three months, alongside a trend increase in weight. Three months of ETI significantly decreased IL-18 (p< 0.0011, p < 0.0001), IL-1ß (p<0.0013, p = 0.0476), IL-6 (p = 0.0109, p = 0.0216) and TNF (p = 0.0028, p = 0.0033) levels in CF serum and following PBMCs stimulation respectively. The corresponding mRNA levels were also found to be reduced in stimulated PBMCs, as well as reduced ASC specks and caspase-1 levels, indicative of NLRP3-mediated production of pro-inflammatory cytokines, IL-1ß and IL-18. While ETI therapy is highly effective at reducing sweat chloride and improving lung function, it also displays potent anti-inflammatory properties, which are likely to contribute to improved long-term clinical outcomes.

Vonoprazan causes symptomatic improvement in non-erosive gastroesophageal reflux disease: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of vonoprazan therapy as compared to conventional proton pump inhibitors (PPIs) or no vonoprazan for non-erosive esophagitis. METHODS: A thorough search was conducted across databases. The primary outcome was to determine the mean variance in the gastroesophageal reflux disease (GERD) score after vonoprazan treatment. Secondary outcomes comprised alterations in the scores for epigastric pain and post-prandial distress, the proportion of patients displaying improvement, and the occurrence of adverse events. Pooled mean differences and relative risks were determined utilizing random effects models. RESULTS: A total of 1,944 articles were screened and nine of them were included. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the GERD score [mean difference: -3.88 (95 % CI: -5.48, -2.28), p < 0.01, i2=95 %]. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the epigastric pain score [mean difference: -3.02 (95 % CI: -5.41, -0.63), p = 0.01, i2=75 %] and post-prandial distress score [mean difference: -2.82 (95 % CI: -3.51, -2.12), p < 0.01, i2=0 %] (all moderate GRADE evidence). Vonoprazan therapy was found to be safe. CONCLUSION: Treatment with vonoprazan could significantly improve symptoms in patients with non-erosive esophagitis or non-erosive GERD.

The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study.

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

Time to improvement of pain, morning stiffness, fatigue, and disease activity in patients with ankylosing spondylitis treated with tofacitinib: a post hoc analysis.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS. METHODS: This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16-48. OUTCOMES: nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1-6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points. RESULTS: 269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4-8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8-24 (12-40) weeks with tofacitinib vs. 24-32 weeks (32 weeks-not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment. CONCLUSIONS: Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03502616, 11 April 2018.

Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. AIM: To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. METHODS: This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. RESULTS: A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. CONCLUSION: VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Persistence and evolution of Pseudomonas aeruginosa following initiation of highly effective modulator therapy in cystic fibrosis.

Today, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given the drastic respiratory symptom improvement experienced by many post-ETI, clinical studies are already underway to reduce the number of respiratory therapies, including antibiotic regimens, that pwCF historically relied on to combat lung disease progression. Early studies suggest that bacterial burden in the lungs is reduced post-ETI, yet it is unknown how chronic Pseudomonas aeruginosa populations are impacted by ETI. We found that pwCF remain infected throughout their upper and lower respiratory tract with their same strain of P. aeruginosa post-ETI, and these strains continue to evolve in response to the newly CFTR-corrected airway. Our work underscores the continued importance of CF airway microbiology in the new era of highly effective CFTR modulator therapy. IMPORTANCE: The highly effective cystic fibrosis transmembrane conductance regulator modulator therapy Elexakaftor/Tezacaftor/Ivacaftor (ETI) has changed cystic fibrosis (CF) disease for many people with cystic fibrosis. While respiratory symptoms are improved by ETI, we found that people with CF remain infected with Pseudomonas aeruginosa. How these persistent and evolving bacterial populations will impact the clinical manifestations of CF in the coming years remains to be seen, but the role and potentially changing face of infection in CF should not be discounted in the era of highly effective modulator therapy.

Vonoprazan 10 mg or 20 mg vs. lansoprazole 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis: A randomized controlled trial.

BACKGROUND: Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. METHODS: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group. CONCLUSION: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE. TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02388737.

Predicting weight gain in patients with cystic fibrosis on triple combination modulator.

BACKGROUND: Cystic fibrosis (CF) is caused by CF transmembrane conductance regulator (CFTR) gene mutations producing dysfunctional CFTR proteins leading to progressive clinical disease. Elexacaftor-tezacaftor-ivacaftor (ETI) remarkably improves lung disease but is associated with substantial weight gain. STUDY DESIGN AND METHODS: We performed a single-center longitudinal study predicting 6-month weight gain after ETI initiation. We used linear mixed effects modeling (LME) to determine association of ETI treatment with changing body mass index (BMI). Using linear regression, we examined BMI prediction models with distinct combinations of main effects to identify a model useful for patient counseling. We used up to eight commonly observed clinical characteristics as input variables (age, sex, percent predicted FEV1 [FEV1%], F508del homozygous state, pancreatic sufficiency, HgbA1c, prior modulator use and prior year number of pulmonary exacerbations). RESULTS: We evaluated 154 patients (19-73 years old, 54% female, FEV1% = 19-121, 0-6 prior year pulmonary exacerbations). LME demonstrated an association between ETI use and weight increases. Exhaustive testing suggested a parsimonious linear regression model well-fitted to data that is potentially useful for counseling. The two variable model shows that on average, BMI decreases by 0.045 (95% Confidence Interval [CI] = -0.069 to -0.021, p < 0.001) for every year of age and increases by 0.322 (CI = 0.142 to 0.502, p = 0.001) for each additional prior year exacerbation at the time of ETI initiation. INTERPRETATION: Young patients with many prior year pulmonary exacerbations likely have the largest 6 month weight gain after starting ETI.

Tofacitinib Treatment for Pretibial Myxedema.

This case report describes tofacitinib treatment for 2 patients with pretibial myxedema.

Retrospective evaluation of toceranib phosphate (Palladia) in the treatment of canine carcinomatosis and mesothelioma.

Canine carcinomatosis (CC) and mesothelioma (CM) are rare but aggressive neoplasms that historically have been associated with poor prognoses. There is limited information regarding treatment for CC and CM. The purpose of this retrospective study was to evaluate the efficacy and tolerability of toceranib phosphate (Palladia) in dogs with CC and CM. Cases were solicited from the American College of Veterinary Internal Medicine (ACVIM) Oncology listserv and retrospectively reviewed. For eligibility, a cytologic and/or histopathologic diagnosis of CC or CM was required. A total of 23 cases were included (CC = 14, CM = 8, both = 1). Eighty-two percent (19/23) of dogs presented with effusion. The best overall response rate (BORR) was 30.4% (13% complete response [CR], 17.3% partial response [PR]). Stable disease (SD) was appreciated in 14 dogs (60.8%) including the four dogs without effusion. The most common toceranib-related adverse events were either Grade 1 and 2 diarrhea or hyporexia. The median progression-free survival (PFS) was 171 days (range, 7-519 days) and overall median survival time (MST) was 301 days (range, 49-875 days) for all dogs. When evaluating dogs solely with effusion, the median PFS and overall MST were 171 days (range, 7-519 days) and 285 days (range, 49-875 days), respectively. This report demonstrates that toceranib is both well tolerated and a potential treatment for CC and CM. A randomised, controlled, prospective study would be needed to objectively assess the survival benefit of toceranib in the management of CC and CM, with and without effusion.

TRPV4 antagonist suppresses retinal ganglion cell apoptosis by regulating the activation of CaMKII and TNF-α expression in a chronic ocular hypertension rat model.

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.

Pancreatic adenocarcinoma treated with surgical resection, toceranib phosphate and firocoxib in a dog: a case report.

Exocrine pancreatic carcinomas are rarely reported in dogs. A ductal pancreatic adenocarcinoma in a 10-year-old intact beagle is described in this report. The diagnosis was made based on clinical signs, imaging (abdominal ultrasound and CT scan) and histopathology. Treatment consisted of partial right lobe pancreatectomy followed by adjuvant therapy with toceranib phosphate (Palladia®) and firocoxib (Previcox®) for six months. The treatment was well tolerated, and the survival time was 445 days. To our knowledge, this is the longest survival reported in the literature for a dog diagnosed with exocrine pancreatic adenocarcinoma. The results described here may contribute to provide a better understanding about this neoplasia and potential treatment options.

Endocrine and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer-Capivasertib-Fulvestrant: ASCO Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).