Real-world Retrospective Study Research Articles

Different dosing strategies of pembrolizumab in the treatment of NSCLC: A real-world retrospective observational study.

e23264 Background: Immune checkpoint inhibitors lack a dose-response relationship, allowing optimisation of dosing strategies that may reduce drug use. Pembrolizumab received its initial regulatory approval for the treatment of non-small cell lung cancer (NSCLC) at weight-based dosing (2 mg/kg every 3 weeks (Q3W)), as employed in pivotal clinical trials demonstrating its efficacy and safety. This dosing regimen was later replaced by the currently approved flat-dosing (200 mg Q3W or 400 mg Q6W) in all indications, potentially increasing drug use. This retrospective observational study evaluates differences in pembrolizumab use for different dosing strategies in a real-world patient cohort. Methods: Overall, 124 advanced NSCLC patients, treated with first-line pembrolizumab monotherapy at a single institution, were included. During the observation period, pembrolizumab flat-dosing was employed, with possible extensions of treatment administrations. Patient and treatment data were obtained from medical records. Duration of treatment was calculated from day 1 of first cycle to last day of last cycle, excluding treatment delays due to adverse events. Pembrolizumab use was calculated for 3 dosing strategies: i) as actually received, ii) as flat-dosing, iii) as body-weight dosing, capped at 200 mg Q3W. It is presented as median dose Q3W and cummulative dose in the whole cohort. Results: Included patients had a median weight of 73 kg (IQR: 65-84) and received a total of 1600 mg of pembrolizumab (IQR: 800-3600) over 24 weeks (IQR: 12-60). The median pembrolizumab dose was i) 190 mg Q3W (IQR: 172-200) as actually received by patients, and would be ii) 200 mg Q3W (IQR: 200-200) in case of flat dosing, and iii) 146 mg Q3W (IQR: 130-168) in case of body-weight dosing. Overall, total pembrolizumab dose in the whole cohort was i) 283,600 mg actually used, and would be ii) 327,800 mg in flat-dosing, and iii) 251,200 mg body-weight dosing, resulting in a 23.4% reduction of drug use in weight-adjusted vs flat-based dosing. Conclusions: Pembrolizumab dosing adjusted to body weight, as initially approved, would reduce drug use vs the currently approved flat-dosing, reaching nearly a 25% reduction in our cohort of patients.

Real-world comparison of the efficacy of three CDK4/6 inhibitors (CDK4/6i) in the first-line treatment of endocrine-sensitive advanced breast cancer (aBC): Single institution experience.

e13080 Background: The combination of CDK4/6i and endocrine therapy (ET) is the standard of care in the first-line treatment of hormone receptor positive (HR+), HER2- aBC. In registrational studies, the progression-free survival (PFS) of all three CDK4/6i ranged from 23.8 to 28.12 months and overall survival (OS) from 53.9 to 66.8. In Croatia, both ribociclib and palbociclib were approved for clinical use in August 2018 and abemaciclib in November 2019. Methods: This retrospective study included patients with endocrine-sensitive HR+, HER2- aBC treated with aromatase inhibitor (AI) and CDK4/6i in the first-line setting between August 2018 and October 2023 at University Hospital Centre Zagreb. Ethics committee approval was obtained before the study was commenced. Patient demographics, clinical presentation, tumor characteristics and treatment data were collected. Real-world PFS (rwPFS) and OS analyses were done with the final data cut-off date of December 31, 2023, using type 1 right censoring. Data were analyzed using the Kaplan-Meier method. Results: Of the 274 patients treated with a combination of CDK4/6i and ET in the first-line setting, 172 with endocrine-sensitive tumors (98 de novo metastatic and 74 with treatment-free interval longer than 12 months) were eligible for the study, of which 41.86% (72/172) received ribociclib, 44.19% (76/172) palbociclib, and 13.95% (24/172) abemaciclib. Overall rwPFS was 48 months (95% CI:35-53). In the abemaciclib group, median rwPFS and OS were not reached in the follow-up period. The rwPFS was 48 (95% CI:27-53) for ribociclib and 47 (95% CI:30-49) for palbociclib. The overall OS was 62 months (95% CI:47-62). Median OS in the ribociclib group was 62 months (95% CI:40-62) and in the palbociclib group 52 (95% CI:42-54) months. Conclusions: The PFS and OS results for palbociclib and ribociclib in this retrospective real-world study correlate with results from randomized clinical trials, confirming some inferiority of palbociclib compared to ribociclib in the context of OS. Due to the later availability of the drug, larger sample size and longer follow-up will be needed to make definitive conclusions on the efficacy of abemaciclib.

Efficacy of first-line dual oral pyrotinib plus capetabine therapy in HER2-positive metastatic breast cancer: A real-world retrospective study.

The combination of dual-targeted human epidermal growth factor receptor 2 (HER2) therapy and chemotherapy is the standard first-line regimen for recurrent/metastatic breast cancer (mBC). However, the toxicity of such combination therapy can lead to some patients being unable to tolerate adverse events or bear treatment costs. As a novel irreversible pan-ErbB receptor TKI (pyrotinib), can the dual oral administration of pyrotinib plus capetabine (PyroC) provide first-line survival benefits and serve as a more affordable treatment option? This real-world retrospective study included patients diagnosed with HER2-positive mBC who received PyroC as a first-line treatment at West China Hospital between May 2018 and July 2023. The survival data and toxicity profiles were reported in this study. A total of 64 patients received PyroC as first-line therapy. The median progression-free survival (PFS) was 19.6 months (95% CI 15.0-27.2), while overall survival (OS) has not yet been reached. Kaplan-Meier analysis indicated that age (≥60, p = 0.03) and metastasis sites (p = 0.004) were related to poor efficacy of PyroC, while there was no relationship between effectiveness and menstrual status, hormone receptor (HR) status or previous treatment with anti-HER2 therapy. Furthermore, the objective response rate (ORR) and disease control rate (DCR) were 79.7% and 98.4%, respectively. Of the patients, 78.1% reported treatment-related adverse events (TRAEs). The predominant adverse events were diarrhea (n = 46, 71.9%) and hand-foot syndrome (n = 10, 15.6%). The dual oral administration regimen (PyroC) has a promising ORR or PFS in HER2-positive mBC patients, with an acceptable safety profile and convenience.

Quantifying the natural growth rate of hepatocellular carcinoma: A real-world retrospective study in southwestern China.

In recent years, approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma (HCC) have been reported in China. Despite the high incidence of HCC, there remains a paucity of data regarding the natural growth pattern and the determination of optimal surveillance intervals specific to the Chinese population. To quantify the natural tumor growth pattern of HCC in regional China. A retrospective analysis was performed on patients from a single institution in Southwest China who had undergone two or more serial dynamic computed tomography or magnetic resonance imaging scans between 2014 and 2020, without having received any anti-cancer therapy. Tumor growth was assessed using tumor volume doubling time (TVDT) and tumor growth rate (TGR), with volumes measured manually by experienced radiologists. Simple univariate linear regression and descriptive analysis were applied to explore associations between growth rates and clinical factors. This study identifies the median TVDT for HCC as 163.4 d, interquartile range (IQR) 72.1 to 302.3 d, with a daily TGR of 0.42% (IQR 0.206%-0.97%). HCC growth patterns reveal that about one-third of tumors grow indolently with TVDT exceeding 270 d, another one-third of tumors exhibit rapid growth with TVDT under 90 d, and the remaining tumors show intermediate growth rates, with TVDT ranging between 3 to 9 months. The identified TGRs support biannual surveillance and follow-up for HCC patients in certain regions of China. Given the observed heterogeneity in HCC growth, further investigation is warranted.

Treatment simplification to optimize cenobamate effectiveness and tolerability: A real-world retrospective study in Spain.

This study aimed to explore the impact of co-antiseizure medication (co-ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy in a real-world setting. This unicentric, retrospective, observational study included adults with focal-onset seizures who had received ≥2 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12-month visits. The number of co-ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs). Thirty-four patients with a median epilepsy duration of 22 years and a median of 15.5 seizures/month were analyzed. The median number of prior ASMs was 12, and the mean number of co-ASMs was 2.9 (SD 1). There was a reduction in seizure frequency/month from baseline to the last visit (p < 0.0001). Between baseline and the end of the study, the mean number of co-ASMs in the per-protocol (PP) population was reduced from 2.9 to 1.6 (p < 0.0001), and DDD was reduced from 3.6 to 1.4 (p < 0.0001). Sodium channel blockers (carbamazepine and lacosamide) and GABAergic drugs (clobazam) were the agents with the most significant reductions in DDD after 12 months. The percentage of patients in the PP population with ≥3 co-ASMs was reduced from 61.8% at baseline to 14.3% at 12 months; 1 patient was receiving CNB as monotherapy at the last visit. At the last visit, 85.7% of the PP population were ≥50% responders, and 33.3% were seizure-free. The percentage of patients with ADRs in the PP population was 71.9% at 3 months and 52.3% at 12 months. Following rational polytherapy, optimization of co-ASM management during CNB treatment allowed high seizure freedom rates despite meaningful reductions in co-medication, while also achieving both good tolerability and patient satisfaction scores in a highly drug-resistant population. Many patients with epilepsy still have seizures, even after being treated with several different epilepsy drugs. In this study of 34 patients from a Spanish clinic, we show that the epilepsy drug cenobamate can reduce the number of seizures in these patients, even after many other epilepsy drugs have failed. We also show that patients treated with cenobamate can reduce the dose or even stop taking certain other epilepsy drugs. This allows them to simplify their treatment and reduce adverse effects while still keeping control of their epilepsy.

Cytisine for smoking cessation: A 40-day treatment with an induction period.

Cytisine is a smoking cessation drug now used worldwide. Most of the data available in the literature predict a 25-day treatment, accepted on the basis of previous clinical experience in Eastern Europe. There are few studies on dosing, and only recently some researchers have tried a longer treatment period. This real-world retrospective cross-sectional study analyzed data collected consecutively from 2015 to 2021, in seven smoking cessation centers in north-central Italy. The aim of this study is to evaluate the effectiveness and tolerability of a 40-day cytisine treatment with an induction phase and a slower reduction schedule. Data were collected from a group of 871 patients treated with cysteine, varenicline, and nicotine replacement therapy (NRT). The sample was not randomized. Behavioral support (4-6 sessions, each lasting 20-30 min, plus the evaluation session) was delivered to all patients. Subgroups taking cytisine (n=543 for 40 days), varenicline (n=281 for 12 weeks), and NRT (n=47 for eight weeks) showed biochemically confirmed smoking abstinence at 6 months of 50.5%, 55.9%, and 51.0%, respectively, with a statistically significant difference between cytisine versus varenicline (p<0.01) but not between cytisine versus NRT (p=0.5597). Adverse events were 4.4% with cytisine and 33.3% with varenicline. Behavioral support was an important factor in effectiveness. This study produced preliminary evidence that the 40-day regimen of cytisine, appears to have less effectiveness in comparison to varenicline but the magnitude of the effect is comparable. The results and tolerability seem to be better than in most other studies.

Clinicopathological features and prognosis of early-onset gastric cancer: a large-scale retrospective real-world study

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

The Effect of Placement and Management of Intrathecal Catheters Following Accidental Dural Puncture on the Incidence of Postdural Puncture Headache and Severity: A Retrospective Real-World Study

(Anaesthesia. 2023;78:1256–1261) Previous studies have come to different conclusions about whether insertion of an intrathecal (IT) catheter after accidental dural puncture (ADP) during epidural anesthesia reduces complications. The most common complication is postdural puncture headache (PDPH), which can have short-term and long-term effects, including decreased breastfeeding and increased risk for postpartum depression, chronic headache, and backache. The usual treatment for PDPH is an epidural blood patch (EBP), which itself can have serious complications. Accidental dural puncture occurs in ∼0.5% to 1.0% of all epidurals. The authors of this study investigated whether IT catheter insertion was associated with a decreased risk of PDPH and a decreased need for EBP.

Efficacy and Safety of Dupilumab in Chinese Elderly Patients with Atopic Dermatitis: A Real-World Study

Introduction: With the aging of the population in China, the prevalence of atopic dermatitis (AD) is high in elderly patients. These patients usually have more comorbidities and they need more effective and safer treatments. Dupilumab is an anti-interleukin-4 (IL-4) receptor monoclonal antibody which was approved for the treatment of moderate-to-severe AD. Methods: Elderly patients (60 years or older) with moderate-to-severe AD who treated with dupilumab were included. Eczema Area and Severity Index (EASI) score, Peak Pruritus Numerical Rating Scale (PP-NRS), EASI-50, EASI-75, and EASI-50 were evaluated. The efficacy in subgroups was also investigated. Results: Fifty-eight patients were enrolled. The EASI score and PP-NRS score were significantly reduced at weeks 4, 16, 28, and 52. 91.2% and 79.4% of the patients achieved EASI-50 and EASI-75 at week 16, respectively. 95.8% and 87.5% patients achieved EASI-50 and EASI-75 at week 52, respectively. Adverse events were reported in 10 (17.2%) patients, and no severe adverse event was reported. Male, older age, and moderate AD (EASI <21) were related to better efficacy. Conclusions: This study demonstrated that dupilumab is effective and safe in elderly patients with AD.

A novel score for early prediction of urinary tract infection risk in patients with acute ischemic stroke: a nomogram-based retrospective cohort study

This study aimed to construct and externally validate a user-friendly nomogram-based scoring model for predicting the risk of urinary tract infections (UTIs) in patients with acute ischemic stroke (AIS). A retrospective real-world cohort study was conducted on 1748 consecutive hospitalized patients with AIS. Out of these patients, a total of 1132 participants were ultimately included in the final analysis, with 817 used for model construction and 315 utilized for external validation. Multivariate regression analysis was applied to develop the model. The discriminative capacity, calibration ability, and clinical effectiveness of the model were evaluated. The overall incidence of UTIs was 8.13% (92/1132), with Escherichia coli being the most prevalent causative pathogen in patients with AIS. After multivariable analysis, advanced age, female gender, National Institute of Health Stroke Scale (NIHSS) score ≥ 5, and use of urinary catheters were identified as independent risk factors for UTIs. A nomogram-based SUNA model was constructed using these four factors (Area under the receiver operating characteristic curve (AUC) = 0.810), which showed good discrimination (AUC = 0.788), calibration, and clinical utility in the external validation cohort. Based on four simple and readily available factors, we derived and externally validated a novel and user-friendly nomogram-based scoring model (SUNA score) to predict the risk of UTIs in patients with AIS. The model has a good predictive value and provides valuable information for timely intervention in patients with AIS to reduce the occurrence of UTIs.

Natural history of SCLC patients treated in third-line and beyond: A retrospective real world study

ObjectivesTo describe treatment patterns and estimate outcomes among real-world small cell lung cancer (SCLC) patients in the US who received three or more lines of therapy. Materials and methodsWe conducted a retrospective analysis of adult patients with SCLC who received a front-line platinum-based regimen and two additional lines of therapy (ie., a cohort of at least three lines of therapy). De-identified patients were selected from a United States Flatiron Health oncology database of electronic health records. Treatment patterns were captured by line of therapy. Outcomes evaluated by line of therapy included real-world overall survival (rwOS), real-world progression free survival (rwPFS), real-world response rate (rwRR) and real-world duration of response (rwDOR). ResultsThe analysis included 326 3L SCLC patients, of which 103 (32 %) received 4L treatment, and 38 % (39/103) of 4L treated received 5L of therapy. Among the 3L cohort, the average age was 67 years, 49 % were male, and nearly all had a history of smoking (96 %). In the 3L setting, the median rwOS was 5.3 months (95 % Confidence Interval (CI): 4.5, 6.0), median rwPFS was 2.5 months (95 % CI: 2.1, 2.7), rwRR was 19.3 % (95 % CI: 15.2, 24.0) and median DOR was 3.4 months (95 % CI: 2.8, 4.4). No differences were seen in outcomes between the overall cohort and a subgroup of patients treated with front-line platinum-based regimen with an anti-programmed cell death ligand 1 (PD-L1) agent (atezolizumab or durvalumab), in each respective line of therapy. ConclusionResults from this large, real-world study of US patients with SCLC in the 3L setting and beyond highlight the poor treatment outcomes in advanced SCLC patients with existing therapies and underscore the dire need for new therapies for SCLC patients.

Helicobacter pylori infection associated with an increased incidence of cholelithiasis: A retrospective real-world cohort study of 50832 patients.

Helicobacter pylori (H.pylori) infection is a bacterial disease of the stomach that has been associated with an increased incidence of cholelithiasis. While the updated German guideline emphasizes the relevance of H.pylori as a pathogen and recommends eradication therapy, systematic data on the association between H.pylori infection, its eradication, and the subsequent diagnosis of cholelithiasis in Germany are missing. A total of 25416 patients with and 25416 propensity score-matched individuals without H.pylori infection were identified from the Disease Analyzer database (IQVIA) between 2005 and 2021. A subsequent diagnosis of cholelithiasis was analyzed as a function of H.pylori infection as well as its eradication using Cox regression models. After 10years of follow-up, 8.0% versus 5.8% of patients with and without H.pylori infection were diagnosed with cholelithiasis (P<0.001). Regression analysis revealed a significant association between H.pylori infection and cholelithiasis (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.33-1.58), which was stronger in men (HR: 1.63; 95% CI: 1.41-1.90) than in women (HR: 1.36; 95% CI: 1.22-1.52). In terms of eradication therapy, both an eradicated H.pylori infection (HR: 1.48; 95% CI: 1.31-1.67) and a non-eradicated H.pylori infection (HR: 1.41; 95% CI: 1.25-1.60) were associated with a subsequent diagnosis of cholelithiasis. The present study reveals a strong association between H.pylori infection and a subsequent diagnosis of cholelithiasis in a large real-world cohort from Germany. Eradication therapy was not associated with a reduced incidence of cholelithiasis in our cohort.

Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes)and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Abstract PO4-05-04: Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study

Abstract Background: In the real world, there are still a large number of HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy with fulvestrant monotherapy in China, especially patients with bone metastases only. It is due to lack of data comparing the effective between Palbociclib combined with AI and fulvestrant monotherapy as initial endocrine therapy. On the other hand, there are economic factors and access issues. According to the National Cancer Center's previous clinical experience, Palbociclib combined with AI is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. Therefore, we collected and summarized the previous clinical data in our center to compare the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. Patients and methods: This is a retrospective real-world study of multicenter studies. It aimed at verifying the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. A total of 392 patients with ≥3 months of follow-up received Palbociclib plus AI or fulvestrant alone in the first-line setting between April 1, 2015 and February 1, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed. Results: After sIPTW adjustment, a median follow-up of 37 months (range 34-40) in the Palbociclib group and 59 months (range 56-61) in those taking fulvestrant alone. Palbociclib combination regiment was associated with significantly longer median rwPFS compared to fulvestrant alone (22.0 vs 14.0 months; HR,0.469;95% CI 0.370–0.594, p&amp;lt; 0·0001). Median OS was not reached in the Palbociclib group and was 57 months (95% CI 54.0–66.0) in the fulvestrant group(HR,0.666; 95% CI 0.437–1.017, p&amp;lt; 0·94). Conclusion: In the real-world population of patients, palbociclib combined with AI endocrine therapy is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. PFS and OS before IPTW PFS and OS after IPTW Table patient characteristics Citation Format: Jian Yue, Xue Wang, Jie Ju, Zixiang Yang, Tong Wei, Peng Yuan, Min Gao, Ling Xu, Yin Guan. Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-04.

Abstract PO2-16-10: Characterising HER2-low status in metastatic breast cancer: a real-world retrospective study of patients at a metropolitan cancer centre in Australia

Abstract Background: Traditionally, breast cancer subtyping has described patients as HER2-negative or HER2-positive, with the latter being those in whom HER2-directed therapies are utilised. A proportion of HER2-negative cancers can be classified as “HER2-low” as they express IHC 1+ or 2+ and are non-amplified on in-situ hybridisation (ISH). Until recently, our widely available HER2-targeted therapies have proven to be ineffective in this subtype. The DESTINY-BREAST04 trial (Modi et al, NEJM 2022) showed progression-free and overall survival efficacy of HER2-directed therapy using the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in HER2-low disease, suggesting a need to identify this population for selected therapy. This study evaluated a real-world population of metastatic breast cancer (MBC) patients treated according to traditional breast cancer subtypes to determine the frequency of HER2-low histology, with a focus on selection of first-line therapy. Methods: This retrospective audit identified patients being treated for MBC at a single tertiary hospital (Austin Health in Melbourne, Australia) over a 3.5 year period. Patients were identified from an electronic database, with a date of last follow-up as August 2022. Medical records were interrogated for clinicopathological information including review of pathology reports for breast cancer subtypes. Traditional breast cancer subtypes were defined as (i) ER positive and HER2-negative (HER2 0 or 1+, or 2+ and non-amplified); (ii) HER2-positive (HER2 3+ and/or amplified) and (iii) TNBC (negative for ER and PgR, and HER2 0 or 1+, or 2+ and non-amplified). Selection and duration of first-line treatment for MBC was also recorded. Results: Between March 2018 and August 2022, 202 MBC patients were identified. Based on traditional subtypes, 126 (62%) were ER positive and HER2-negative, 46 (23%) were HER2-positive, 26 (13%) were TNBC and 4 (2%) were unknown. In the total population, 87 (43%) were classified as having HER2-low disease based on retrospective pathology reports. HER2-low represented 61% of ER positive, HER2-non amplified patients and 45% of TNBC patients. Metastatic specimen data was known for 172 cases and of these, 95 patients (55%) were re-biopsied on metastatic progression. This occurred more commonly with HER2-positive (81%) and ER positive HER2-negative (78%) primaries. The most common change in subtype was loss of ER, which occurred in 7 patients (3%). Changes in HER2 status occurred in 29 (14%) of patients, most commonly as either an increase from 1+ to 2+ or decrease from 1+ to 0. HER2-low status remained consistent for 67% of patients who underwent biopsy on recurrence. For patients with ER positive HER2-negative MBC, first-line combination therapy with a CDK4/6 inhibitor + AI was preferred (51%), followed by single agent endocrine therapy (30%) and chemotherapy (17%). The majority (84%) of HER2-positive patients received first-line dual HER2 therapy (trastuzumab and pertuzumab) with taxane chemotherapy. Half of TNBC patients received upfront chemotherapy, with physician preference being capecitabine (45%). There was no significant difference in PFS between the HER2-low vs. HER2-0 cohorts, for either ER positive or TNBC subtypes. No patients in this series were treated based on HER2-low definition due to no funded access to such therapies at the time. Conclusion: HER2-low has emerged as an identifier for patients who may respond to HER2-directed therapies using ADCs such as T-DXd. However, its clinical significance as a discrete clinical subtype remains uncertain. In this retrospective audit, HER2-low patients were identified in both ER positive and TNBC subtypes. Dynamic changes in HER2 staining occurred infrequently. Further evaluation is needed to address whether HER2-low expression provides any prognostic value and whether prospective reporting of HER2-low status may alter how these new HER2-directed therapies are used in future. Citation Format: Michelle Li, Belinda Yeo. Characterising HER2-low status in metastatic breast cancer: a real-world retrospective study of patients at a metropolitan cancer centre in Australia [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-10.

Abstract PO4-02-11: Optimizing Taxane-based Chemotherapy in Breast Cancer: Retrospective study comparing 4 cycles of TC to 6 cycles of TC

Abstract Breast cancer remains one of the most prevalent cancers among women worldwide. First-line chemotherapy options include anthracycline (AC-T) and Taxane (TC) based regimens. While anthracycline-based chemotherapy is most commonly used, the use of anthracycline-sparing regimens is also approved. The US Oncology 9735 trial conducted in the mid 2000s showed that four cycles of docetaxel and cyclophosphamide (TC4) were superior to four cycles of Doxorubicin and cyclophosphamide (AC). The follow-up ABC trials compared six cycles of TC(TC6) to AC-T. This trial showed that while AC-T was superior to TC, the difference was modest. AC-T has remained the standard of care, but TC is an acceptable option. One retrospective analysis involving 143 patients showed TC4 was non-inferior to TC6, and suggested that TC4 had fewer adverse events; however, statistical significance was not reached. The question remains whether six cycles of TC is required, or if four cycles is adequate. Methods: Patient information was retrieved from the EMR of a large private oncology group. The EMR was screened for all breast cancer patients who began treatment with TC between 1/1/2011 and 12/31/2021. Patients were required to have continuous follow-up, documented up to at least 6/30/2022. Only patients receiving TC as the first-line setting were included, while patients with metastatic disease were excluded. Adjusted Kaplan Meier curves for overall survival (OS) and disease-free survival (DFS) were generated. A log-rank test was used to determine the statistical difference between the two curves. OS was defined from the date of the last chemotherapy given to death. DFS is defined from the date of the last chemotherapy given to disease recurrence. The Chi-square analysis test of homogeneity was conducted to evaluate the differences in reported symptoms. Statistical analysis was completed with IBM SPSS version 29. Ethical approval was obtained from The Brooklyn Hospital Center Institutional Review Board. Results: A total of 376 charts were reviewed, out of which 224 met the criteria for inclusion. Of these 191 patients received TC4 and 33 received TC6. TC4 patients were noted to be older than TC6 patients. There were a higher percentage of hormone-positive cancers in the TC4 group while the TC6 group had a larger proportion of triple-negative breast cancers. There was a larger proportion of stage III patients that received TC6 than in TC4. TC6 patients were also noted to receive neo-adjuvant chemotherapy at a substantially higher rate. A greater proportion of patients in the TC4 group received breast-conserving surgery, with radiation than the TC6 group. TC6 had a completion rate of 76 % (Table 1). There was a significant difference in DFS noted between TC4 and TC6 (p = 0.016) with TC6 patients having a higher rate of relapse. No difference was noted in the overall survival. No differences were seen in side effects between TC4 and TC6, however, there was a trend toward high rates of neutropenia, anemia, and neuropathy seen in the TC6 group (Table 2). Conclusions: This real-world retrospective study reviewed patients who received TC in a large community oncology practice. The study reaffirms conclusions seen in previous retrospective studies conducted in the academic setting that there is no difference in overall survival when using six cycles of TC compared to four cycles of TC. Slight detriment was seen in the DFS setting when using TC6 however the small sample size along with the larger proportion of patients with stage III disease make it challenging to interpret this finding. There was a trend towards higher toxicities with TC6 that did not reach significance. Until a prospective randomized study comparing four vs six cycles of TC is conducted no definitive conclusions can be drawn, however, this study contributes to the current body of evidence that four cycles of TC is adequate and could potentially improve the quality of life of patients with early breast cancer. Table. Patient characteristics Patient characteristics including age, hormone status, stage, type of surgery, radiation, and treatment setting. Table. Adverse effects Adverse effect information obtained from physician documentation, and CBC reports documented at time of treatment with TC. Citation Format: Amith Ahluwalia, Michelle Koifman, Jaspreet Nannar, Bhavya Vachhani, Kanwal Ashraf, Maxim Shulimovich. Optimizing Taxane-based Chemotherapy in Breast Cancer: Retrospective study comparing 4 cycles of TC to 6 cycles of TC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-11.

Adherence and recommended optimal treatment to Azvudine application for the treatment of outpatient COVID-19 patients: A real-world retrospective study

BackgroundAzvudine was approved for the treatment of coronavirus disease 2019 (COVID-19) in China and has been widely used since the outbreak in December 2022. However, real-world research on the adherence of Azvudine is lacking. Additionally, limited research exists on determining the optimal duration for Azvudine treatment. MethodsWe studied adult patients with COVID-19 who got Azvudine or supportive treatment at an outpatient department between December 19, 2022 and January 5, 2023. The enrolled patients were divided into two groups: the Azvudine group, which received Azvudine, and the control group, which only received supportive care. We recorded their information and analyzed it using descriptive statistics. The primary outcome of this study was the compliance of outpatients with Azvudine, and the secondary outcome of this study was the optimal duration of Azvudine. Inverse probability weighting (IPW) was used to address the imbalance between groups when comparing the optimal duration of Azvudine, and Cox regression to evaluate the effect of Azvudine on the 28-day disease progression rate. ResultsWe enrolled a total of 882 patients, of which 382 received Azvudine. Among the patients, 94.0 % (359) had good compliance, and non-compliance was primarily attributed to dosage errors. Azvudine appeared to have a beneficial therapeutic effect when administered for at least 7 days. ConclusionsOutpatients have relatively good compliance with Azvudine, and optimal therapeutic effects were observed with the recommended duration of at least 7 days.

Efficacy and safety of inactivated SARS-CoV-2 vaccination in COVID-19-associated pneumonia among patients with rheumatic and musculoskeletal diseases: A real-world retrospective observational study.

To identify the effectiveness and safety of inactivated SARS-CoV-2 vaccines in rheumatic and musculoskeletal diseases (RMDs) patients. RMD patients with COVID-19 in Jiangsu Province were polled between December 8, 2022, and February 1, 2023. Information on demographics, disease characteristics, antirheumatic drug use, vaccination status and survival state were collected. COVID-19-associated pneumonia was the primary outcome. The effect of COVID-19 immunization on RMD patients was assessed using multivariate logistic regression, and the adverse events (AEs) following vaccination were evaluated. Among 592 RMD patients with COVID-19, 276 (46.6%) individuals experienced COVID-19-associated pneumonia, and 290 (49.0%) patients were injected with inactivated vaccines. In multivariate logistic regression analysis, vaccines reduced the incidence of COVID-19-associated pneumonia, and receiving booster vaccine was an independent protective factor for COVID-19-associated pneumonia in RMD patients (OR 0.64, 95% CI 0.41-0.98, p = .034). In particular, inactivated vaccines have a protective impact on RMD patients with a high risk of developing pneumonia, including those aged 45 years and older (OR 0.53, 95% CI 0.34-0.83), and who have lung involvement (OR 0.43, 95% CI 0.23-0.82). The total AEs rate of vaccines was 13.9% (40/290), only 11 (3.8%) experienced the recurrence or deterioration of RMDs, and no serious AEs occurred. Inactivated COVID-19 vaccines were safe and effective in reducing the risk of COVID-19-associated pneumonia of RMD patients in China.

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence insitu hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study

BackgroundThe prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level.MethodsAccording to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs.ResultsIndependent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05).ConclusionThe linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.