Efficacy Data Research Articles

Systematic literature review of asthma biologic self-administration enhanced by a patient perspective

BackgroundSeveral biologics for the treatment of severe asthma are available as self-administration devices. ObjectivePerform a systematic literature review (SLR) to understand the use, benefits and challenges of these self-administration devices. MethodsElectronic databases and conference proceedings were searched using terms for asthma, biologic treatment, and at-home/self-administration (GSK study 213094). Publications were scanned for relevance using pre-specified Population, Intervention, Comparison, Outcomes and Study design (PICOS) criteria. Data on efficacy, safety, patient experience and economic outcomes were extracted; study quality was assessed. A first-hand patient perspective was obtained. ResultsThirty-five of 504 records met the inclusion criteria. Across four Phase III studies, ≥95% of biologic self-administrations were successful based on pre-defined criteria. At-home self-administration was preferred over in-clinic administration by 43–96% of patients across five studies. Most patients (≥89%) in two Phase III studies reported completing self-administration easily without repeated reference to instructions; high proportions of patients (≥98%) were confident in their ability to self-administer their biologic and ≥96% rated it as ‘extremely’, ‘very’ or ‘moderately’ easy to self-administer. Across 16 studies reporting efficacy data, there was evidence of reduced blood eosinophil counts and improved asthma control with biologic self-administration, with improved health-related quality of life shown across six studies. Economic outcomes data were limited. From a patient perspective, autonomy is the major benefit of self-administration. ConclusionWhile more evidence is needed, this SLR provides consistent evidence of high injection success rates, and supported by a patient perspective, preference for self-administration of biologics among patients with severe asthma.

Targeting GPRC5D With Talquetamab: A New Frontier in Bispecific Antibody Therapy for Relapsed/Refractory Multiple Myeloma.

To evaluate the pharmacology, clinical efficacy, safety, dosing, administration, and clinical implications of talquetamab-tgvs, a novel bispecific antibody, in the treatment of relapsed or refractory (R/R) multiple myeloma (MM). A comprehensive English-language literature search of PubMed and Clinicaltrials.gov from January 2000 to May 2024 was conducted using the terms talquetamab, Talvey, JNJ-64407564, and "Multiple Myeloma." Relevant clinical trials, guidelines, and prescribing information were systematically reviewed and analyzed. Talquetamab-tgvs received accelerated approval from the United States Food and Drug Administration based on results from the pivotal phase I/II MonumenTAL-1 clinical trial, which demonstrated an overall response rate of nearly 74% in key cohorts. The median progression-free survival was 7.5 months in the 0.4 mg/kg weekly dosing cohort and 11.9 months in the 0.8 mg/kg biweekly dosing cohort. Treatment-related adverse events (AEs) included cytokine release syndrome, skin- and nail-related AEs, dysgeusia, infections, and immune effector cell-associated neurotoxicity syndrome. As a first-in-class anti-GPRC5D T-cell-redirecting bispecific antibody, talquetamab-tgvs represents a compelling treatment option for patients with R/R MM who have received at least 4 prior lines of therapy. No head-to-head clinical trials have been conducted comparing talquetamab-tgvs to other T-cell-redirecting therapies. While talquetamab-tgvs showed significant efficacy in the pivotal MonumenTAL-1 trial, long-term safety and efficacy data are needed. Additional clinical trials are necessary to establish the optimal timing, sequencing, patient population, and overall role of talquetamab-tgvs in the rapidly evolving treatment landscape of R/R MM.

A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group evaluates the safety and other key features of new platform technology vaccines, including nucleic acid (RNA and DNA) vaccines. This manuscript uses the BRAVATO template to report the key considerations for a benefit-risk assessment of the coronavirus disease 2019 (COVID-19) mRNA-based vaccine BNT162b2 (Comirnaty®, or Pfizer-BioNTech COVID-19 vaccine) including the subsequent Original/Omicron BA.1, Original/Omicron BA.4–5 and Omicron XBB.1.5 variant-adapted vaccines developed by BioNTech and Pfizer to protect against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Initial Emergency Use Authorizations or conditional Marketing Authorizations for the original BNT162b2 vaccine were granted based upon a favorable benefit-risk assessment taking into account clinical safety, immunogenicity, and efficacy data, which was subsequently reconfirmed for younger age groups, and by real world evidence data. In addition, the favorable benefit-risk assessment was maintained for the bivalent vaccines, developed against newly arising SARS-CoV-2 variants, with accumulating clinical trial data.

Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial.

Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. Open-label trial with 2 treatment arms. Pediatric Endocrine Clinic at Stanford. A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models. Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.

Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma

ABSTRACT Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy.

Preliminary Safety and Efficacy Data of Combination Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Adriamycin, Prednisone (Pola-R-CHP) in Patients With Diffuse Large B-Cell Lymphoma (DLBCL) in the Standard-of-Care Setting: A Single-Center Experience

Preliminary Safety and Efficacy Data of Combination Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Adriamycin, Prednisone (Pola-R-CHP) in Patients With Diffuse Large B-Cell Lymphoma (DLBCL) in the Standard-of-Care Setting: A Single-Center Experience

National Vaccination Coverage Among Adolescents Aged 13-17 Years - National Immunization Survey-Teen, United States, 2023.

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines.

Intravaginal artesunate pessaries for treatment of cervical intraepithelial neoplasia 2/3 among HIV-positive and HIV-negative women in Kenya: Study protocol for a pilot trial.

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer. This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Figure 1 illustrates the study schema. Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women. ClinicalTrials.gov identifier: NCT06165614.

U-MET: Utility-Based Dose Optimization Approach for Multiple-Dose Randomized Trial Designs

The advent of dose optimization has led to a paradigm shift in oncology clinical trials to find the optimal biologic dose (OBD). Phase 1/2 trials with randomized doses can facilitate additional investigation of the identified OBD in a targeted population by incorporating safety and efficacy data. We propose to compare randomized doses by extending the Bayesian optimal interval phase 1/2 (BOIN12) approach, an OBD-finding design in which a utility is used to account for risk-benefit tradeoffs. Specifically, we used the BOIN12 standardized mean utilities in a hypothesis testing framework, in which frequentist and Bayesian inference were evaluated to compare the standardized mean utilities across doses and identify the OBD. We performed simulation studies and a hypothetical oncology study to compare the proposed BOIN12 utility-based extension (U-MET) design with an empirical design. The results demonstrated that the U-MET design has satisfactory operating characteristics for selecting the OBD. We recommend using the U-MET design as the primary dose comparison approach, or alternatively as supportive evidence, for optimal dose selection.

Omalizumab and Dupilumab for the Treatment of Bullous Pemphigoid: A Systematic Review.

Background: Bullous pemphigoid (BP) is an autoimmune disease characterized by the appearance of very pruritic subepidermal blisters. It appears mostly in the elderly and is associated with multiple comorbidities, which makes its management and treatment difficult. The purpose of this systematic review is to compile current information on published cases of BP treated with omalizumab (omalizumab) and dupilumab (dupilumab) in order to obtain information on clinical efficacy and safety data available. Methods: A literature search of all cases of BP treated with omalizumab/dupilumab published in the literature up to January 2024 was performed using the Pubmed database. After an exhaustive search, a total of 61 studies encompassing 886 patients met the inclusion criteria and were included in the review. Results: The majority of patients with BP treated with omalizumab/dupilumab presented a significant improvement in symptomatology, being very safe drugs with minimal side effects. The main limitation of the presented review is the quality of the included studies, most of them being case series or individual cases. The development of studies with a higher level of scientific evidence in the near future would be of great interest. Conclusions: Both omalizumab and dupilumab appear to be effective options for treating BP in patients refractory to other pharmacological therapies. They are drugs with a good safety profile and the adverse reactions associated with their use are infrequent and generally mild.

Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab–ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial

The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor. This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing. Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group. The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival. The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development.

Supervised Disulfiram Should Be Considered First-line Treatment for Alcohol Use Disorder.

Despite the prevalence of alcohol use disorder (AUD) in the United States, the armamentarium of FDA-approved medications available for AUD treatment is remarkably small. Disulfiram, 1 of only 3 approved medications, is consistently designated as a second-line option in national treatment guidelines, citing inconsistent evidence, lack of patient preference, and safety concerns. These concerns, however, stem from a misguided interpretation of the evidence that exclusively relies upon double-blind randomized controlled trials (RCT). When viewed instead as both a medication and a behavioral intervention, open-label RCTs become a more appropriate research method, yielding overwhelmingly favorable efficacy data for disulfiram, and supervised disulfiram, in particular. With these data in mind, supervised disulfiram should be redesignated as a first-line intervention in both treatment guideline creation and clinical pathway tools. The addiction medicine community can no longer afford to neglect this critical therapeutic resource.

Single-center analysis of a real-world cohort of patients with metastatic urothelial carcinoma evaluated by NGS: molecular landscape and efficacy of targeted therapies.

To describe the molecular profile of a real-world cohort of patients with metastatic urothelial carcinoma (mUC) and to evaluate the benefit of next-generation sequencing (NGS) panels in guiding therapy in patients with mUC and the outcomes of DNA-matched treatments recommended by a multidisciplinary molecular tumor board (MMTB). This was a single-center analysis of a real-world cohort of adult patients with mUC included in an ongoing trial that aimed to evaluate the clinical utility of NGS for solid tumors. Genomic analysis was performed for each patient, most of them using the Ion Torrent Oncomine Focus Assay. Genomic results were discussed during MMTB meetings. We included 43 patients with mUC treated with platinum-based combinations and immunotherapy. Twenty-five patients (58.1%; 95% CI 43.4-72.9) had at least one tumor pathogenic alteration. The MMTB classified 16 (48.5%) of the 33 tumor pathogenic alterations found in our real-world cohort of mUC patients as ESCAT I, which is the maximum grade of actionability. After excluding patients who were not candidates for targeted therapies, the MMTB provided guidance on matched therapy for seven patients. Among these patients, three achieved a partial response for an overall response rate of 42.9%, a median progression-free survival of 7.3months (95% CI 6.7-7.9) and a median overall survival of 10.9months (95% CI 2.4-19.5). We recommend that all patients with mUC undergo NGS at diagnosis given the high percentage of patients with pathogenic alterations in our real-world cohort and the efficacy data of patients treated with targeted therapies.

Advancing research and development of anti-infectives for children: A clinical development perspective

The HIV treatment landscape for adults has progressed dramatically in recent decades; however, paediatric populations continue to experience delayed and limited access to effective and safe antiretroviral therapy options. Despite current incentive programmes, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 wk). Regulatory approval of drug formulations and dosing in children may lag behind adult approvals by years. Formulation and trial design adjustments complicate paediatric drug development, all of which are vital to accommodate for physiological differences, organ maturation, and rapid weight gain, which are most significant in the youngest children. To facilitate more rapid anti-infective drug development for paediatric populations, regulatory agencies provide guidelines that include extrapolating efficacy and safety data from relevant populations; using pharmacokinetic (PK) bridging and modelling to reduce sample sizes and limit the number of PK studies needed before efficacy analyses; and enrolling age- or weight-based cohorts in parallel rather than sequentially for clinical trials. Ensuring access to approved drugs poses an additional challenge, as uncertainty in demand leads to manufacturing and supply complexity with potentially higher costs that can be a barrier to uptake. Here we summarise challenges in drug development for children living with HIV, which are not unique to antiretrovirals. We aim to propose strategies for how model-based approaches and global partnerships can overcome some of these barriers to accelerate paediatric drug development, with particular reference to HIV, and how lessons learnt from HIV could be extended to other anti-infectives.

Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Upadacitinib in Children with Severe Atopic Dermatitis

PurposeThis study aims to characterize the pharmacokinetics, safety, tolerability, and exploratory efficacy of upadacitinib, an oral Janus kinase inhibitor approved for treating moderate to severe atopic dermatitis (AD) in adults and adolescents, in children with severe AD. MethodsIn an open-label, multiple-dose, Phase 1 study, pediatric patients with severe AD from two age groups (2 to <6 years and 6 to <12 years) received bodyweight-based dosing regimens of upadacitinib using either twice-daily immediate-release (IR) oral solution or once-daily extended-release (ER) tablets. A pharmacokinetic assessment was conducted on Day 7 of the study, which was followed by a long-term safety and exploratory efficacy evaluation for up to 108 weeks. The results reported here are based on an interim analysis when the study had completed enrollment and pharmacokinetic assessment. FindingsA total of 35 patients were enrolled and received upadacitinib. The maximum upadacitinib plasma concentration was attained within a median time of 0.5 to 2 hours and 2 to 2.5 hours for the IR oral solution and ER tablet formulations, respectively. Upadacitinib functional half-life was generally shorter with IR oral solution relative to ER tablets. Upadacitinib apparent oral clearance decreased with decreasing body weight in the pediatric patients enrolled in this study. Upadacitinib was generally safe and well tolerated. The most common (≥3 patients) adverse events were upper respiratory tract infection, COVID-19 infection, headache, abdominal discomfort, vomiting, asthma, and cough. No new safety risks were identified compared to the known safety profile for upadacitinib in adults and adolescents. In the 30 patients with available exploratory efficacy data at Week 12, 36.7% achieved validated Investigator's Global Assessment scale for AD score of 0 or 1 (Validated Investigator Global Assessment for AD 0/1), and 70.0% had Eczema Area and Severity Index (EASI) improvement of at least 75% (EASI 75). ImplicationsThe characterized pharmacokinetic profiles in this study, together with the observed safety and exploratory efficacy results, support further investigation of the current upadacitinib dosing regimen in future confirmatory Phase 3 clinical trials in children with AD.Clinical Trial Number: NCT03646604, registered 2018-08-23

Effect of Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 Inducer, on the Pharmacokinetics of Vatiquinone.

Vatiquinone is a small molecule inhibitor of 15-lipoxygenase in development for patients with Friedreich's ataxia. The objective of this analysis was to determine the effect of a cytochrome P450 isoform 3A4 (CYP3A4) inhibitor and inducer on vatiquinone pharmacokinetics (PKs). The coadministration of 400mg of vatiquinone with 200mg of itraconazole (a CYP3A4 inhibitor) resulted in increased maximum observed concentration (Cmax) of vatiquinone and systemic exposure (AUC0-inf) by approximately 3.5- and 2.9-fold, respectively. The coadministration of 400mg of vatiquinone with 600mg of rifampin (a CYP3A4 inducer) resulted in decreased vatiquinone Cmax and AUC0-inf by approximately 0.64- and 0.54-fold, respectively. The terminal half-life of vatiquinone was not affected by itraconazole or rifampin. These clinical study results confirm the in vitro reaction phenotyping data that shows that CYP3A4 plays an important role in vatiquinone metabolism. The result of this analysis together with phase 3 efficacy and safety data, population PK analysis, and the exposure-response relationship will determine if the extent of vatiquinone changes in the presence of CYP3A4 inhibitors and inducers are considered clinically relevant.

Real-world outcomes with lurbinectedin in second-line and beyond for small cell lung cancer in Korea.

211 Background: Small-cell lung cancer (SCLC) accounts for approximately 10~15% of all lung cancers and is characterized by a strong tendency for early metastasis, and a poor prognosis. Most patients are diagnosed with extensive disease, with only one-third presenting with earlier-stage disease amenable to potentially curative multimodality therapy. Before the advent of lurbinectedin in 2020, only few options existed for treating patients with SCLC that had progressed after first-line therapy. The sole available second-line option for metastatic SCLC was topotecan, which is associated with hematological toxicities and only modest efficacy. Although lurbinectedin has been added to the arsenal against metastatic SCLC, real-world data on its efficacy has been scarce due to its recent implementation. In this study, we investigated the demographics and clinical outcomes of metastatic SCLC patients treated with lurbinectedin in Korea. Methods: Patients with metastatic SCLC who had failed first-line therapy were identified (n=51) at Yonsei Cancer Center, Seoul, Republic of Korea, and received lurbinectedin at a starting dose of 3.2mg/kg. Efficacy data, including investigator-assessed tumor response, progression data, survival, and demographic information, were recorded. Results: A total of 51 patients were treated with lurbinectedin at a single center in Korea. Thirty-four patients were eligible for assessment. The median age of diagnosis was 68. The overall objective response rate and disease control rate were 20% and 47%, respectively. For patients treated with lurbinectedin in the second-line therapy, the ORR and DCR were 12% and 15% respectively, while the ORR was 18% and DCR was 29% for patients in beyond third-line of therapy. The median progression-free survival was 1.8 months (95% CI 0.38 to 2.08), and the median overall survival was 2.8 months (95% CI 0.55 to 2.70). A patient group with a history of smoking showed prolonged overall survival and disease control rate. The most common adverse effects related to lurbinectedin were anemia (55%), leukopenia (53%), nausea (35%), loss of appetite (25%), general weakness (19%), neutropenia (12%), dizziness (6%), alopecia (6%), phlebitis (3%), thrombocytopenia (3%), pneumonia (3%). Conclusions: The real-world data of lurbinectedin in SCLC patients suggests that it is still a viable option in this disease area with dismal prognosis. [Table: see text]

Avelumab plus axitinib for first-line treatment of advanced renal cell carcinoma: A real-world ambispective RAVE-Renal study.

117 Background: In a phase 3 JAVELIN Renal 101randomized study, the combination of avelumab and axitinib demonstrated a significant improvement in progression-free survival (PFS; median 13.9 months) and objective response rate (ORR; 59.3%) among patients with metastatic clear-cell renal cell carcinoma (mRCC), leading to FDA approval as a first-line therapy. In our ambispective observational RAVE-Renal study, real-world data were gathered to assess the practical application and outcomes associated with the use of avelumab and axitinib in clinical settings. Methods: Patients were recruited from 13 sites, with data collected anonymously online. Key inclusion criteria were untreated mRCC and a minimum age of 18 years. Safety and efficacy assessments were conducted in all patients who received at least one dose of avelumab and axitinib. The primary endpoints included ORR and PFS, while secondary endpoints encompassed overall survival (OS) and the incidence of treatment-related adverse events (TRAEs). Results: At the time of data cutoff (February 03, 2024), a total of 125 patients were enrolled and treated. Median age was 61 years (range, 37-74). Patients were predominantly men (74.3%), previously nephrectomised (81.4%), had 2 and more metastatic sites (77.1%) including bone (24.3%), liver (15.7%), and brain (3%) metastases. IMDC risk was evaluated in 102 patients. Among these patients, 36 (35.3%) were categorized as having favorable risk, 50 (49%) as intermediate risk, and 16 (15.7%) as poor risk. The median number of avelumab infusions was 7 (range, 1-29). Table summarizes efficacy and safety data. Conclusions: The real-world study of first-line avelumab and axitinib therapy reveals comparable ORR and PFS to those observed in the pivotal clinical trial among patients with mRCC. The combination was well tolerated. Further follow-up of patients in the study is ongoing. Clinical trial information: KCRB01012022 . [Table: see text]

Focused allergic rhinitis practice parameter for Canada.

Allergic rhinitis (AR) is a prevalent disease in Canada that affects both children and adults. Several guidelines for the management of AR have been published by professional allergy societies worldwide. However, there are regional differences in the clinical management of AR, and regulatory approval of some AR pharmacotherapies varies among countries. Thus, six research questions specific to the treatment of AR in Canada were identified for this focused practice parameter. Reviews of the literature published since 2016 were conducted to obtain evidence-based support for the responses of the Work Group to each research question. In response to research question 1 "In patients with symptoms indicative of AR, is serum-specific IgE sufficient to identify candidates for immunotherapy or is a skin prick test mandatory?" the Work Group concluded that either sIgE testing or skin prick test are acceptable for diagnosing AR and guiding immunotherapy. In response to research question 2 "When taking into account the preferences of the patient and the prescriber (stakeholder engagement) should second-generation oral antihistamine (OAH) or intranasal corticosteroid (INCS) be first line?" the Work Group concluded that existing guidelines generally agree on the use of INCS as a first-line therapy used for AR, however, patient and provider preferences and considerations can easily shift the first choice to a second-generation OAH. In response to research question 3 "Is a combination intranasal antihistamine (INAH)/INCS formulation superior to INCS plus OAH? Do they become equivalent after prolonged use?" the Work Group concluded that that the combination INAH/INCS is superior to an INCS plus OAH. However, there was insufficient evidence to answer the second question. In response to research question 4 "Do leukotriene receptor antagonists (LTRA) have a greater benefit than OAH in AR for some symptoms to justify a therapeutic trial in those who cannot tolerate INCS?" the Work Group concluded that LTRAs have inferior, or at best equivalent, daytime or overall symptom control compared with OAH, but LTRAs may improve nighttime symptom control and provide benefits in patients with AR and concomitant asthma. In response to research question 5 "Should sublingual immunotherapy (SLIT) tablets be considered first-line immunotherapeutic options over subcutaneous immunotherapy (SCIT) based on the evidence of efficacy?" the Work Group concluded that the choice of SLIT or SCIT cannot be made on efficacy alone, and differences in other factors outweigh any differences in efficacy. In response to research question 6 "Based on efficacy data, should ALL patients seen by an allergist be offered SLIT or SCIT as a treatment option?" the Work Group concluded that the efficacy data suggests that SLIT or SCIT should be used broadly in patients with AR, but other clinical concerns also need to be taken into consideration.

Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n = 25. RAS mutation: n = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n = 25. Complete response: n = 0, partial response: n = 14 (56%), stable disease: n = 8 (32%), progressive disease: n = 3 (12%), early tumor shrinkage: n = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.