Search

Jessie R Groothuis1, Jon P Fryzek1,2, Doris Makari1, Duane Steffey2, William J Martone11MedImmune, LLC, Gaithersburg, MD, 2Exponent, Menlo Park, CA, USAObjective: Infants with chronic lung disease of infancy (CLDI) are at high risk for severe respiratory syncytial virus (RSV) illness requiring hospitalization. Palivizumab was first licensed in 1998 for the prevention of RSV disease in high-risk infants, including those with CLDI. We performed a retrospective cohort study of all hospitalized children with CLDI aged

Background: Cardiovascular (CV) comorbidities and concurrent medications with risk of heart rate-corrected QT interval (QTc) prolongation can impact treatment decisions and safety discussions for patients with breast cancer. However, limited data are available regarding their prevalence in patients with HR + /HER2- metastatic breast cancer (mBC). We evaluated the prevalence of CV comorbidities, the use of concurrent medications with risk of QTc prolongation, and treatment patterns in patients with newly diagnosed HR + /HER2 - mBC., Methods: This retrospective analysis utilized claims data from Merative™ Marketscan® Commercial and Medicare databases. Claims-based algorithms identified patients with newly diagnosed HR + /HER2- mBC between January 2016 and December 2022. The index date was defined as the first date of an mBC claim during this period. For each patient, data on pre-existing CV comorbidities and first-line treatments were captured for 12 months before and 6 months after the index date, respectively., Results: A total of 6525 patients with newly diagnosed HR + /HER2 - mBC were identified. At mBC diagnosis, 61.7% of patients had ≥ 1 CV comorbidity. Of patients with CV comorbidities, 22.5% and 30.6% took 1 or ≥ 2 medications, respectively, with risk of QTc prolongation. First-line use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors increased from 22.1% of patients with CV comorbidities diagnosed in 2016-2017 to 31.5% of those diagnosed in 2018-2022., Conclusions: We found that CV comorbidities and use of medications with risk of QTc prolongation were common in patients with newly diagnosed HR + /HER2 - mBC. These factors should inform treatment decision-making (including CDK4/6 inhibitor selection), safety discussions with patients, and CV monitoring., Competing Interests: Declarations. Ethics approval and consent to participate: This study used Health Insurance Portability and Accountability Act–compliant and deidentified data, which did not meet the criteria for human subject research as specified in the United States Department of Health and Human Services 45 Code of Federal Regulations Part 46. Therefore, neither institutional review board approval nor informed consent was required. Consent for publication: Not applicable. Competing interests: • SD reports consulting for Pfizer Inc., AstraZeneca, Gilead Sciences, Myocardial Solutions, Novartis, and Lilly. • AG reports being a ZERO Cancer Health Equity Task Force member; American Heart Association Council on Clinical Cardiology and Genomics and Precision Medicine Cardio-Oncology Committee member and site principal investigator; and an advisory board member for Myovant, Pfizer Inc., and Novartis. • HM reports consulting for Novartis, Lilly, AstraZeneca, Gilead, Genetech, and Pfizer Inc. • DM, RM, IA, and BL are employees of, and stockholders in, Pfizer Inc. • SS is an employee of and stockholder in Pfizer Inc., and a stockholder in Roche. • MF reports grant support from Medtronic and AstraZeneca; and has consulted for AstraZeneca, AbbVie, Johnson & Johnson, Janssen, Pfizer Inc., and Zoll., (© 2025. The Author(s).)

Background: Patients with cardiovascular disease (CVD) comorbidities are often excluded from participating in breast cancer clinical trials. Consequently, data to inform treatment decisions for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and CVD are limited., Objective: We compared the effectiveness of first-line palbociclib plus an aromatase inhibitor (AI) vs an AI alone and evaluated palbociclib treatment patterns in patients with HR+/HER2- mBC and CVD in routine clinical practice., Methods: Data from the Flatiron Health Analytic Database were captured for patients with HR+/HER2- mBC and CVD who initiated first-line treatment with palbociclib plus an AI or an AI alone between February 2015 and March 2020 (data cutoff: September 30, 2020). Overall survival (OS), real-world progression-free survival (PFS), and treatment patterns were evaluated., Results: Of the 469 patients with identifiable CVD, 160 received palbociclib plus an AI, and 309 received an AI alone. After stabilized inverse probability treatment weighting, both median OS (40.7 vs 26.5 months; hazard ratio [HR], 0.732 [95% CI, 0.537-0.997]; P = .048) and median real-world PFS (20.0 vs 12.5 months; HR, 0.679 [95% CI, 0.512-0.900]; P = .007) were significantly prolonged in patients treated with palbociclib plus an AI vs an AI alone. Among patients with a documented palbociclib starting dose, 78.5% started palbociclib at 125 mg/day, and 38.6% experienced dose adjustment., Conclusions: In this real-world analysis, first-line palbociclib plus an AI was associated with improved effectiveness compared with an AI alone in patients with HR+/HER2- mBC and CVD., Trial Registration: NCT05361655 (ClinicalTrials.gov)., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved patient survival in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) in clinical trials and real-world studies. However, investigations of survival gains in broader HR+/HER2- mBC populations using epidemiological approaches are limited., Methods: This retrospective study used SEER registry data to assess breast cancer-specific survival (BCSS) in patients diagnosed with HR+/HER2- de novo mBC from 2010 to 2019. Kaplan-Meier and Cox proportional hazards models were used to compare BCSS in patients diagnosed before (2010‒2013 with follow-up to 2014) and after (2015‒2018 with follow-up to 2019) the 2015 guideline recommendations for CDK4/6i use. A comparison was made to patients with HR+/HER2-positive (HER2+) de novo mBC, for which no major guideline changes occurred during 2015-2018., Results: Data from 11,467 women with HR+/HER2- mBC and 3260 women with HR+/HER2+ mBC were included. After baseline characteristic adjustment, patients with HR+/HER2- mBC diagnosed post-2015 (n = 6163), had an approximately 10% reduction in risk of BC-specific death compared with patients diagnosed pre-2015 (n = 5304; HR = 0.895, p < 0.0001). Conversely, no significant change was observed in HR+/HER2+ BCSS post-2015 (n = 1798) versus pre-2015 (n = 1462). Similar results were found in patients aged ≥ 65 years., Conclusion: Using one of the largest US population-based longitudinal cancer databases, significant improvements in BCSS were noted in patients with HR+/HER2- mBC post-2015 versus pre-2015, potentially due to the introduction of CDK4/6i post-2015. No significant improvement in BCSS was observed in patients with HR+/HER2+ mBC post-2015 versus pre-2015, likely due to the availability of HER2-directed therapies in both time periods., (© 2024. The Author(s).)

Aim: To evaluate the impact of palbociclib treatment on health-related quality of life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic breast cancer (mBC) in both the clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify clinical trials and real-world evidence studies up to June 2023 that reported HRQoL outcomes in patients with HR+/HER2- aBC or mBC treated with Palbociclib. Results: 15 unique studies reported across 35 records were identified. Of these, seven were randomized controlled trials (RCTs), three were single-arm clinical trials and five were real-world evidence (RWE) studies. HRQoL was generally found to be maintained in patients with HR+/HER2- aBC or mBC across RCTs, single-arm clinical trials and RWE studies. HRQoL measures across instruments, study types and line of therapy, were largely reported to be at least maintained if not improved from baseline among patients treated with palbociclib and were observed to be comparable or better in the palbociclib group versus monotherapy control arm in RCTs. Similar results were seen for treatment-related outcomes (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), and important individual patient outcomes, including pain, fatigue and physical functioning. Findings were also consistent across key clinical characteristics (visceral metastases, neutropenia), as well as patient populations often underrepresented in clinical trials (Asian patients, older adults). Conclusion: Overall, current evidence suggests that HRQoL is largely preserved with the addition of palbociclib to endocrine therapy in patients with HR+/HER2- aBC or mBC across study types and populations.

Purpose: A prognostic model for overall survival of post-platinum patients with metastatic urothelial carcinoma receiving PD-1/PD-L1 inhibitors is necessary as existing models were constructed in the chemotherapy setting., Materials and Methods: Patient level data were used from phase I/II trials evaluating PD-L1 inhibitors following platinum based chemotherapy for metastatic urothelial carcinoma. The derivation data set consisted of 2 phase I/II trials evaluating atezolizumab (405). Two phase I/II trials that evaluated avelumab (242) and durvalumab (198) comprised the validation data sets. Cox regression analyses evaluated the association of candidate prognostic factors with overall survival. Stepwise selection was used to select an optimal model using the derivation data set. Discrimination and calibration were assessed in the avelumab and durvalumab data sets., Results: The 5 prognostic factors identified in the optimal model using the atezolizumab derivation data set were ECOG-PS (1 vs 0, HR 1.80, 95% CI 1.36-2.36), liver metastasis (HR 1.55, 95% CI 1.20-2.00), platelet count (HR 2.22; 95% CI 1.54-3.18), neutrophil-to-lymphocyte ratio (HR 1.94, 95% CI 1.57-2.40) and lactate dehydrogenase (HR 1.60, 95% CI 1.28-1.99). There was robust discrimination of survival between low, intermediate and high risk groups. The c-statistic was 0.692 in the derivation and 0.671 and 0.773 in the avelumab and durvalumab validation data sets, respectively. A web based interactive tool was developed to calculate the expected survival probabilities based on risk factors., Conclusions: A validated 5-factor model has satisfactory prognostic performance for survival across 3 PD-L1 inhibitors to treat metastatic urothelial carcinoma after platinum therapy and may assist in stratification, interpreting and designing trials incorporating PD-1/PD-L1 inhibitors in the post-platinum setting.

In July 2014, the Committee on Infectious Diseases (COID) updated their guidance on the use of palivizumab, recommending against use in preterm infants 29 to 35 weeks' gestational age (wGA). A primary data source cited to support this significant change was the low respiratory syncytial virus (RSV) hospitalization rate observed in the subpopulation of preterm (<37 wGA) infants evaluated from 2000 to 2005 through the New Vaccine Surveillance Network (NVSN). Here we critically appraise the preterm infant data from the NVSN in the context of data regarding the use of palivizumab in this same time period. Data from the NVSN, an analysis of Florida Medicaid data, and a national survey of US in-hospital palivizumab administration demonstrated that during 2001 to 2007, palivizumab was administered to 59% to 83% of preterm infants born at <32 wGA and 21% to 27% of all preterm infants (<37 wGA). When the NVSN data regarding incidence of RSV hospitalization in preterm infant subgroups were evaluated as a function of chronologic age, preterm infants <32 wGA showed a paradoxical increase in RSV hospitalization with older age, with the highest risk of RSV hospitalization occurring at 18 to 23 months of age. This pattern is most consistent with a reduction in RSV hospitalizations in <32 wGA infants in the first 12 to 18 months of life due to high palivizumab use at these young ages. The NVSN data were not designed to and cannot accurately describe RSV disease burden in preterm infants given the small size of the analyzed subpopulation and the high use of palivizumab during the study period.

Introduction: The American Academy of Pediatrics (AAP) Committee on Infectious Diseases issued updated guidance on respiratory syncytial virus (RSV) prophylaxis in 2014. This report models the potential impact of the new guidance on RSV outcomes in preterm infants 29-34 weeks' gestational age (wGA) without chronic lung disease in the United States., Methods: The number of preterm infants was estimated using 2012 natality data. Palivizumab utilization prior to the 2014 guidance update was estimated using 2013-2014 specialty pharmacy utilization data. Low, moderate, and high RSV hospitalization (RSVH) rates as well as average hospital length of stay, intensive care unit (ICU) admissions and mechanical ventilation (MV) frequencies were derived from published observational studies. Palivizumab efficacy was derived from two randomized clinical trials. RSV events that would be attributable to the 2014 guidance change were calculated for preterm infants 29-31 and 32-34 wGA., Results: Annual number of infants 29-34 wGA surviving the neonatal period was estimated at 123,687. Of these, an estimated 44,712 (37%) would receive palivizumab based on the 2012 guidance. The annual number of RSVH among infants 29-34 wGA would increase from 3580 under the 2012 guidance to 6166 under the 2014 guidance based on moderate rates. This would result in an additional 24,440 hospitalization days, 1162 ICU admissions, and 584 MV events among this population., Conclusions: Based on published historical and contemporary data on RSVH rates in preterm infants 29-34 wGA, the 2014 AAP guidance is expected to result in additional burden to the healthcare system and families of preterm infants. The impact of the new guidance will be difficult to detect among the overall infant population, particularly in settings without routine testing for RSV, but the impact will be substantial for the small high-risk population affected by the changes., Funding: AstraZeneca.

Introduction: Lower respiratory tract infection (LRTI) is the leading cause of infant mortality globally in post-neonatal infants (i.e., 28-364 days of age). Respiratory syncytial virus (RSV) is the most commonly identified pathogen for infant LRTI and is the second most important cause of death in post-neonatal infants. Despite 50 years of RSV vaccine research, there is still no approved vaccine. Therefore, passive immunity with the monoclonal antibody palivizumab is the sole regulatory-approved option for the prevention of serious LRTI caused by RSV in pediatric patients at high risk of RSV disease., Methods: We conducted a comprehensive systematic literature review of randomized controlled trials (RCTs), open-label non-comparative clinical trials, and prospective observational studies/registries, and summarized the evidence related to the safety, efficacy, and effectiveness of palivizumab., Results: The efficacy of palivizumab, as measured by the relative reduction in RSV-related hospitalization rate compared with placebo ranged from 39% to 78% (P < 0.05) in the 2 pivotal RCTs. A meta-analysis of the RSV-related hospitalization rate from 5 randomized placebo-controlled trials yielded an overall odds ratio of 0.41 (95% CI, 0.31-0.55) in favor of palivizumab prophylaxis over placebo (P < 0.00001). Low rates of RSV-related hospitalizations were observed in palivizumab recipients consistently over time in more than 42,000 pediatric subjects across 7 RCTs, 4 open-label non-comparative trials, and 8 observational studies/registries conducted in 34 countries. In addition, among palivizumab-prophylaxed subjects with breakthrough RSV LRTI, rates of intensive care unit admission and mechanical ventilation from RSV hospitalization also were low and consistent across studies. With respect to safety, no differences were observed between palivizumab and placebo in the blinded RCTs., Conclusion: Rates of RSV hospitalizations and RSV hospitalization-related endpoints in pediatric subjects who received prophylaxis with palivizumab were low and constant over time and across RCTs, open-label non-comparative trials, and observational studies/registries.

Objective: To assess the pharmacokinetics and safety of liquid palivizumab compared with lyophilized palivizumab., Methods: This phase 2, randomized, double-blind crossover study included premature infants aged ≤6 months born ≤35 weeks gestational age. Patients were randomized in a 1:1 ratio to receive a single 15 mg/kg intramuscular dose of liquid (sequence A group) or lyophilized (sequence B group) palivizumab on Day 0. Patients crossed over to receive the alternate formulation on Day 30. Serum palivizumab and antidrug antibody (ADA) levels were measured on Day 0 (predose), Day 30 (before the dose of alternate formulation), and Day 60 (30 days after the dose of alternate formulation). Patients were followed for safety through Day 60 (30 days after the dose of alternate formulation)., Results: A total of 153 infants were randomized into the study (sequence A 75; sequence B 78). Sequence A and sequence B trough serum palivizumab levels were similar on Day 30 (51.7 and 49.1 µg/mL, respectively) and Day 60 (84.8 and 87.2 µg/mL, respectively). The ratio of the geometric means using both Day 30 and Day 60 serum concentrations was 1.040 (90% CI 0.998-1.083), which was within the prespecified bioequivalence range of 0.8-1.25. Adverse events (AEs) were similar between the palivizumab liquid and lyophilized groups and within each treatment sequence. Serious AEs (SAEs) were experienced by 3% of infants in both liquid palivizumab and lyophilized palivizumab groups. None of the SAEs were determined to be related to study drug. Among the 124 infants (81% of total) evaluated for ADA, 2 (1.6%) tested positive for ADA at Day 60 (1 in each of sequence A and B)., Conclusion: Liquid and lyophilized formulations of palivizumab were bioequivalent with similar safety profiles in infants.

Introduction: To avoid the need for reconstitution required by lyophilized palivizumab, a liquid formulation was developed. This study assessed the safety and antidrug antibodies (ADA) of the liquid formulation of palivizumab compared with the lyophilized formulation., Methods: This phase 4, randomized, double-blind, multicenter study included children with chronic lung disease of prematurity who were ≤24 months of age and children born prematurely with a gestational age of ≤35 weeks who were ≤6 months of age at randomization. Subjects were randomized 1:1 to 15 mg/kg of either liquid or lyophilized palivizumab administered via intramuscular injection every 30 days for a total of 5 injections. Safety was assessed based on serious adverse events (SAEs). ADA to palivizumab was assessed using blood collected at baseline and at a time point between study days 240 and 300., Results: A total of 413 subjects were included in the analyses. The incidence of SAEs reported was 8.5% with liquid palivizumab and 5.9% with lyophilized palivizumab; none were deemed drug-related. The reported SAEs were consistent with expected conditions in this pediatric age group; there was no increase in respiratory syncytial virus (RSV) disease with liquid palivizumab. At study days 240-300, antipalivizumab antibodies were detected in none of the subjects in the liquid palivizumab group and in 1 subject in the lyophilized group. The true ADA percent positive, based on the upper limit of the 95% confidence interval (CI), was <1.5% for both treatments combined., Conclusion: The frequency of detection of ADAs was low. The true ADA percent positive for both treatment groups combined based on the upper limit of the 95% CI was <1.5%. The type and frequency of SAEs reported were as expected, and there was no evidence of an increase in RSV disease with liquid palivizumab.

Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial virus (RSV) disease in preterm infants ≤ 35 wGA. However, some RSV guidelines currently recommend stopping palivizumab after 3 months of age in the midst of the RSV season. This article evaluates the need for full-season dosing by reviewing the pharmacokinetic properties of palivizumab and RSV hospitalization (RSVH) risk as a function of chronologic age. Precise human palivizumab protective levels are not established. Clinical trials show significant interpatient variability in palivizumab serum trough concentrations. Partial season dosing is associated with increased risk of RSVH. For late-preterm infants, data suggest that the risk of RSVH remains elevated through at least 6 months of age. Monthly, full-season palivizumab dosing provides the only empirically proven protection from RSVH. In conclusion, late-preterm infants are at significant risk for RSVH through at least 6 months of age and would benefit from dosing throughout the RSV season.

The prevalence of respiratory syncytial virus in children presenting to US emergency departments with lower respiratory tract infection or apnea (N = 4172) was evaluated outside the traditional respiratory syncytial virus season (September to October and April to May) relative to January to February. The Mid-Atlantic and Southeast demonstrated positivity rates in September to October comparable with rates observed during January to February.

Background: Respiratory syncytial virus (RSV), a leading viral respiratory pathogen worldwide, has 2 major subtypes, A and B., Objective: To describe the temporal and geographic distribution and parameters of disease severity associated with RSV A and B in the United States., Methods: A US multicenter active surveillance study was conducted in emergency departments (EDs) during 2 RSV seasons. Infants <1 year of age presenting to the ED with symptoms of lower respiratory tract infection or apnea were enrolled. RSV subtypes were detected in nasal swabs by reverse transcriptase polymerase chain reaction., Results: Of 4248 patients enrolled, 4172 patients were evaluable; 32.4% of patients were positive for any RSV subtype in season 1 and 29.9% in season 2. RSV A and B were detected in each region studied. More patients presented to the ED with RSV A than with RSV B (853 [20.4%] versus 453 [10.9%], respectively); RSV A-positive patients were more likely to be admitted to the hospital or intensive care unit (47.7%, versus RSV B, 35.8%; P < 0.0001); hospitalized RSV A-positive patients were less likely to be prescribed antibiotics (32.4%, versus RSV B, 47.8%; P < 0.001)., Conclusions: This is the largest epidemiologic study in EDs reporting trends in RSV subtypes. RSV subtypes A and B were documented in both seasons across all US regions studied and detected in September to May. The results of this study support suggestions from smaller studies that RSV A may be more virulent than RSV B; however, more quantitative assessments of disease severity are needed.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of prematurity, is the major cause of pulmonary disease in infants. The pathophysiology and management of BPD have evolved over the past four decades as improved neonatal intensive care unit (NICU) modalities have increased survival rates. The likelihood for developing BPD increases with the degree of prematurity and reaches 25-35% in very low-birth-weight and extremely low-birth-weight infants. BPD affects many organ systems, and infants with BPD are at increased risk for rehospitalization and numerous complications following NICU discharge. The management of BPD and medically related problems, particularly during the first 2 years of life, remains a continuing challenge for parents and healthcare providers. It is important that a multidisciplinary team consisting of the neonatologist/attending physician, primary care physician, and other specialized support staff work in concert and meet regularly to provide continuity of care and accurate patient assessments.

Severe RSV disease, manifested as bronchiolitis or pneumonia, is the leading cause of hospitalization of infants younger than 1 year of age in the United States. Infants born 35 weeks or less GA are particularly at high risk of severe RSV disease, which may result in frequent NICU admissions or long hospital stays and additional health care utilization over the first 12 months of life. This care is costly--infants 33 to 36 weeks GA with a history of RSV hospitalization incur costs that are nearly 5 times as much as costs for 33 to 36 weeks GA infants with no history of RSV hospitalization. Managed care payers should be cognizant of the potential ramifications of severe RSV disease in infants. Developing a proactive RSV management strategy can help improve health outcomes and reduce unnecessary hospital resource use.

A survey was sent to the emergency room and laboratory directors of 400 randomly selected US hospitals to assess the diagnostic testing practices for respiratory syncytial virus and influenza virus in children. The results demonstrate that the majority of hospitals routinely perform viral testing for both viruses and use virology testing practices appropriate for the reasons reported for testing.