Introduction. The Eastern Cooperative Oncology Group Performance Status Scale (ECOGPSS, hereafter abbreviated as PS) is widely used to select appropriate patients for clinical trials. PS is also used to narrow down patients in research studies using electronic health record (EHR) sources. Patient status against PS is often not measured in clinical practice, resulting in missing records of “PS grade” in EHR sources. The missing records of PS grade leads to a diluted patient cohort due to insufficient narrow down, making it difficult for researchers to generate convincing evidence from EHR sources. We have thus tried to develop a classification model using trained machine learning (ML), which enables us to supplement the missing records of PS grade with high accuracy.

Aim. This study aims to develop ML-based models to classify the status of non-small cell lung (NSCLC) patients at initial diagnosis into PS grade.

Methods. A cohort of 10,525 patients diagnosed with stage III-VI NSCLC with one or more records of PS grade at diagnosis was identified from ConcertAI Patient360™, deeply curated, de-identified EHRs and linked claims in the US. We developed classification models to discriminate between favorable (0-1) and unfavorable (2+) PS grade using logistic regression, gradient boosting classifier (GBC), K-neighbors classifier, and etc, with 14 variables recorded before medication.

Results. As preliminary results, the classification model using GBC classified patient status into PS grade, giving an AUC-ROC of 0.59 providing accuracy of 0.80. Key variables for classification were cancer stage, Charlson Comorbidity Index, number of metastatic sites, and age.

Discussion. There is room for improvement of the model to classify patient status given the low AUC-ROC value. For better classification, further studies are underway including broader variables like medication sequence or outcomes including timing of disease progression or death.

Key words: performance status, classification, machine learning, electronic health record

Introduction
There is limited evidence regarding the use of levetiracetam in post-stroke seizures. Considering that inadequate seizure control for post-stroke seizure patients increases the risk of disability and mortality, it is crucial to understand whether levetiracetam can effectively serve as a suitable alternative anti-seizure drug in this population.

Aims
To evaluate the risks of seizure recurrence and mortality of levetiracetam compared to valproic acid in post-stroke seizure patients.

Methods
This retrospective cohort study was conducted using the National Health and Insurance Research Database in Taiwan. Patients who received the first inpatient seizure diagnosis between January 1, 2012 and December 31, 2020, and were newly prescribed monotherapy levetiracetam or valproic acid were included. Patients were required to have had at least one stroke diagnosis within two years before the seizure diagnosis. Levetiracetam users were the exposure group and valproic acid users were the reference group. Inverse probability of treatment weighting was applied to balance the baseline covariates between groups. Outcome measures included risks of seizure rehospitalization, all-cause mortality, and the need for switching to or adding alternative anti-seizure drugs. Outcomes between the groups were compared using Cox-proportional hazard models.

Results
We included 740 levetiracetam and 786 valproic acid users in this study. Levetiracetam was associated with lower risks of seizure rehospitalization (HR: 0.85; 95% CI: 0.72-0.99) and the need for switching to or adding alternative anti-seizure drugs (HR: 0.66; 95% CI: 0.57-0.77) compared to valproic acid. However, no significant difference in the risk of all-cause mortality was observed between the two study groups.

Discussions
Our study indicates that levetiracetam had a lower seizure rehospitalization risk and comparable mortality to valproic acid. Levetiracetam users were also more likely to persist with their medication without requiring alternative anti-seizure drugs. Therefore, levetiracetam may be a suitable option for post-stroke seizure patients.

Introduction:
The anti-sclerostin antibody drug, romosozumab, is a novel option in osteoporosis treatment. It has both bone anabolic and antiresorptive effects by inhibiting the suppression of Wnt signaling. However, hypocalcemia has been reported as an adverse effect in some patients receiving romosozumab treatment. The risk factors for romosozumab-induced hypocalcemia were not well established.

Aims:
This study aims to investigate the impact of romosozumab on hypocalcemia and factors associated with hypocalcemia upon romosozumab administration.

Methods:
Using multi- institutional databases in Taiwan, we conducted a population‐based nested case-control study. We included patients with a prescription for romosozumab between November 2021 and March 2024. Patients without baseline creatinine and calcium level were further excluded due to important prognostic factors. We included patients who experienced hypocalcemia during the medication usage period or within one month after medication cessation and matched each patient experiencing an event with up to 2 control subjects. The cohort entry date and index date were defined as first date of romosozumab and occurrence of hypocalcemia, respectively. We used conditional logistic regression to assess risk factors for hypocalcemia.

Results:
There were 306 romosozumab users experiencing 97 hypocalcemia events (31.6%).
Longer cumulative romosozumab use was not associated with an increased risk of hypocalcemia (cumulative uses: OR, 0.92 [95% CI, 0.79-1.08]; more than 6 months uses: OR, 0.87 [95% CI, 0.25-3.00]). Patients with CKD were associated with an increased risk of hypocalcemia (OR: 2.46 [95% CI, 1.01-5.97])

Discussion:
This nested case-control study found that CKD was associated with hypocalcemia during romosozumab administration, and there was no significant correlation between cumulative dose and hypocalcemia. These findings demonstrate that in osteoporotic patients with CKD requiring romosozumab therapy, close monitoring of serum calcium levels and vigilance for hypocalcemia symptoms may be essential to prevent the occurrence of severe hypocalcemia.

Introduction: Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments.
Aims: To compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine).
Methods: A retrospective population-based cohort study was conducted using a primary care electronic health record database in the UK - IQVIA Medical Research Data (IMRD-UK). Patients with bipolar disorder who were newly prescribed lithium, antipsychotics or antiepileptics between 1993 and 2019 were identified. Risk of fractures was compared between lithium and non-lithium groups with propensity score fine stratification weighting.
Results: Among 40697 patients with bipolar disorder from 1993-2019 identified from a primary care electronic health record database in the UK, 13385 were new users of mood stabilizing agents (lithium: 2339; non-lithium: 11046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95% CI 0.44-0.98). The results were similar when comparing lithium with antipsychotics (HR 0.72, 95% CI 0.49-1.07) and mood stabilizing antiepileptics (HR 0.75, 95% CI 0.42-1.34), respectively.
Discussion: Lithium was associated with a lower risk of fractures compared with non-lithium treatment among patients with bipolar disorder. The effect might be from the protective effect of lithium or increased risk of fractures due to other non-lithium treatments. Our findings could help inform better treatment decisions for bipolar disorder and lithium’s protective effect on fractures should be taken in consideration for patients with high risk of fractures.

Introduction: The details of the advantages of long-acting injectable antipsychotics (LAIs) over oral antipsychotics (OAs) in real-world setting remain unclear.
Aims: We compared the effectiveness of LAIs and OAs in treating schizophrenia, focusing on whether the benefits of LAIs over OAs are evident even in the prevalent new user design and on effect heterogeneity.
Methods: We conducted a prevalent new user cohort study using two administrative claims databases in Japan. We included patients with schizophrenia initiated on LAIs and matched patients on OAs using time-dependent propensity score matching. We compared the risks of psychiatric hospitalization and treatment discontinuation based on hazard ratios (HRs) using the Cox proportional hazards model. Effect heterogeneity was evaluated using subgroup analyses with factors of psychiatric hospitalization history and proportion of days covered (PDC).
Results: In total, 2520 patients using LAI and OA were identified as matched cohorts. LAIs were associated with a higher psychiatric hospitalization risk than OAs (HR, 1.41; 95% confidence interval [CI], 1.06–1.88) in the entire population; however, LAIs were associated with lower risk in the group with a low PDC and psychiatric hospitalization history (HR, 0.51; 95% CI, 0.30–0.89). LAIs were associated with a lower risk of treatment discontinuation than OAs (HR, 0.76; 95% CI, 0.66–0.87) in the entire population; in the subgroup analyses, a consistent trend was observed in all strata (LAIs had a lower risk).
Conclusions: Using a prevalent new user design, this study confirmed that LAIs have an advantage regarding treatment continuity. LAIs had higher psychiatric hospitalization risk than OAs in the entire population; however, this study suggested the presence of effect heterogeneity due to psychiatric hospitalization history.

Introduction
While medication waste may be caused by medication oversupply, the degree of medication oversupply and its related factors are unclear in Japan.
Aims
This study aimed to quantify oversupply of chronic disease medications per patient and to identify its related factors and causes.
Methods
A retrospective cohort study using a large insurance claims database was conducted for patients aged ≥ 55 years who received one or a combination of major five classes of chronic disease medications in FY 2019. Medications with the same ingredient and the same specification were treated as the same medication. Medication oversupply was defined as a medication possession ratio > 1.0. The proportion of oversupplied patients, and the excess days and costs of oversupplied medications were calculated. Logistic regression models were utilized to analyze related factors with the two cohorts, excessive oversupply (≥ 30 excess days/year) and normal supply (≤ ±15 excess days/year), for each class. Causes of oversupply were classified by reviewing history of prescription and dispensing for 50 individuals randomly selected from excessive oversupply cohort.
Results
The proportions of oversupplied patients and excessively oversupplied patients were approximately 16% and 1–2% for all medication classes, respectively. Three-quarters of the oversupplied patients had ≤ 14 excess days/year. However, there were a patient with 983 excess days/year of oversupplied medication and a patient with nearly 90000 yen/year of oversupplied medication costs.
Notable related factors for all classes were greater frequency of early supply, inpatient prescription, and greater number of ingredients taken concomitantly. The most prominent category of causes was ‘Early supply of medications prescribed by a single facility’, irrespective of classes.
Discussion
The factors and causes of oversupply could reflect unique features of Japanese healthcare system. The findings suggest the need of developing measures for reducing medication oversupply.

Introduction: Telomeres are sequences of nucleotides that maintain cell stability but shorten with each cell division. When telomeres reach a critical short length, cells stop dividing (senescence) or die (apoptosis). Telomere length is used as a marker of aging and can be influenced by factors such as stress, lifestyle, nutrition, and hormones. Women undergo hormonal changes during menstruation, pregnancy, and menopause, which can affect telomere length.

Aims: Our study aimed to examine the relationship between nutritional status and telomere length in adult women.

Methods: This cross-sectional design study, conducted in 2023, involved 93 women aged 30-45 in Padang City, Indonesia. Nutritional status was assessed by examining body weight, height, and fat percentage. Body fat percentage was analyzed by a bioelectrical impedance analyzer. Furthermore, blood samples were analyzed using O'Callaghan and Fenech's technique to measure telomere length. The data was analyzed by using one-way ANOVA test.

Results: This study found that the mean age of the subjects was 38.34 ± 4.9 years. Among the subjects, 26 had normal nutritional status (normal-weight lean, NWL), 11 had normal-weight obesity (NWO), and 56 were obese (Ob). The mean telomere lengths for NWL, NWO, and Ob subjects were 432.08 ± 205.8 bp, 412.46 ± 143.9 bp, and 401.63 ± 137.0 bp, respectively. Statistical analysis revealed no significant difference in telomere length among the three groups (p > 0.05).

Discussion/conclusion: Our findings demonstrated that although there were no significant differences between the three groups, there was a tendency for telomere length to decrease as nutritional status increased. Further research is needed to explore other factors related to telomere length in Indonesian women.

Keywords: aging, nutritional status, telomere, women

Introduction:
Monitoring the incidence of intussusception after rotavirus vaccination is recommended by the World Health Organization. In Japan, the linkage of vaccination records with medical claims data covering the entire population will be developed in a few years for vaccine safety monitoring. However, there is no validated claims-based algorithm to identify patients with intussusception.

Aims:
We aimed to validate claims-based algorithms to identify patients with intussusception from Japanese claims data.

Methods:
The target population was those who visited one hospital in Japan at least once between June 2017 and August 2023. Their claims data were used to develop algorithms. Ultrasound test results data were used as the reference standard for true patients with intussusception. 'Claims-based cases' were defined by three patterns: Algorithm #1 diagnosis code ICD-10 K56.1 on inpatient claims, Algorithm #2 ultrasound test codes accompanying #1; Algorithm #3 intussusception treatment codes accompanying #2. ‘True cases’ were defined by diagnosis based on ultrasound test results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with their 95% confidence intervals were calculated for each algorithm.

Results:
The target population comprised 243,432 patients (female 54.4%, mean age 49.0 years). The number of 'true cases' from the reference standard was 17 patients (female 41.2%, mean age 1.0 years). The number of 'claims-based cases' identified by algorithms #1, #2 and #3 was 116, 51, and 27 respectively. The sensitivities and PPVs were 94.1% (82.9%, 99.9%) and 13.8% (7.5%, 20.1%) for algorithm #1, 82.4% (64.2%, 99.9%) and 27.5% (15.2%, 40.0%) for algorithm #2, and 70.6% (48.9%, 92.2%) and 44.4% (25.7%, 63.2%) for algorithm #3, respectively. All specificities and NPVs were greater than 99.9% (99.9%, 99.9%).

Discussion:
This study showed algorithms with high sensitivities and specificities, although PPVs were low. We will add data from other hospitals and continue to find more suitable algorithms.

Introduction
The first-line agent for the treatment of ulcerative colitis is 5-aminosalicylic acid (5-ASA). About 10% of patients taking 5-ASA are deemed to develop a condition called “5-ASA intolerance,” in which they have difficulty taking 5-ASA continuously due to adverse effects. The number of patients developing 5-ASA intolerance seems to be on the rise. We can provide safer treatment if we can identify patients at high risk of developing 5-ASA intolerance.

Aims
The purpose of this study was to develop and internally validate a prediction model for the occurrence of 5-ASA intolerance among Japanese ulcerative colitis patients.

Methods
We analyzed data from December 2016 to March 2023 using the payer database held by JMDC Inc. The occurrence of 5-ASA intolerance was defined when the 5-ASA oral prescriptions were discontinued within 180 days of the initial prescription and a diagnosis of ulcerative colitis was made after the discontinuation. Predictors were selected from the candidate factors based on expert opinions and the results of univariate Cox regression analysis. A prediction model was developed using the Cox proportional hazards model, considering the nonlinearities of continuous variables and interactions between variables. Internal validity of the model was assessed from two points; 1) The model’s accuracy by a calibration plot, 2) The model’s discrimination ability by optimism-corrected c-index with bootstrapping.

Results
The sample size was 10,749 with 1,038 (9.7%) events. The selected predictors were gender, age, 5-ASA brands, and prescription dose. The developed prediction model along with its internal validity will be reported in the session.

Conclusion
In this study, a prediction model for the occurrence of 5-ASA intolerance among Japanese ulcerative colitis patients was developed and internally validated. This model can help provide safer treatment.

Background: Erythropoietin was linked to bone metabolism in preclinical studies, but the relationship remained inconclusive in humans. Therefore, the association between erythropoiesis-stimulating agent (ESA) use and bone metabolism needs further investigation.

Methods: Using the electronic health record from the Hong Kong Hospital Authority, we conducted a nested case-control study among patients with chronic kidney disease (CKD) using ESA between 2005 and 2022. Incidence cases of osteoporotic fracture were matched with up to 10 fracture-free controls on age, sex, and year of fracture incidence. We estimated the odds ratio (OR) and 95% confidence interval (CI) for the association of ESA with fracture risk using conditional logistic regression, adjusted for unbalanced CKD-related risk factors after matching.

Results: 959 osteoporotic fracture cases were identified and matched with 9262 fracture-free control. The duration of ESA treatment was associated with an increased risk of osteoporotic fracture [OR per year of ESA treatment: 1.27, 95% CI: 1.21-1.33, p<0.001]. An increase in accumulated ESA dose was associated with increased fracture risk, but the effect was attenuated after adjustment for ESA treatment duration. Consistent findings were observed in the spine and hip fracture subtypes. Similar results were observed in subgroup analysis stratified by age, sex, CKD stages, and dialysis history, and in the sensitivity analysis with adjusted prescription duration for iron supplementation and average haemoglobin level since initiation of ESA treatment.

Conclusion: This study suggests a potential relationship between the use of ESA and bone metabolism among patients with CKD. The management of anaemia management in CKD patients with ESA might warrant a shorter treatment duration.

Substance use disorders (SUD) rank among the top ten most disabling conditions globally. Additionally, drug-related issues can lead to increased morbidity and mortality, resulting in a substantial burden.
To explore signals for SUD in adults, focusing on the anatomical main group level in the Anatomic Therapeutic Chemical (ATC) Classification.
We utilized VigiBase data from January 1, 2000, to October 27, 2023. VigiBase, maintained by the Uppsala Monitoring Centre for the World Health Organization, was used to identify cases of individuals over 18 years old with Standard Medical Dictionary for Regulatory Activities Queries (SMQs) targeting “Drug abuse, dependence, and withdrawal”. Non-cases were individuals over 18 years old with any other SMQs. Drug exposure was categorized based on "suspected" and "interacting" reports, and the frequency of drugs focused on the 1st level of ATC code. The reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated using logistic regression models.
Among 17,783,005 reports with ATC codes, 260,145 were identified as cases. Most of these cases were within the 18-44 age group (38.81%), with females accounting for 58.08%. A significant proportion of the reports (78.35%) originated from the Americas. 'Nervous system' drugs were the most frequently reported cases (27.98%), followed by ‘Dermatologicals’ (14.71%). However, ‘Antiinfectives for systemic use’ were most frequently reported among non-cases (22.16%). 'Benzodiazepine derivatives' exhibited an ROR of 4.18(95% CI, 4.09–4.27). The stratified analysis, 'Benzodiazepine derivatives' showed higher ROR in females (ROR, 3.84; 95% CI, 3.73–3.95) and individuals younger than 75 years old (ROR, 4.30; 95% CI, 4.21–4.40).
Including neurologic, dermatologic, and psychiatric drugs, further investigations for detecting novel signals of SUD are needed to enhance public health surveillance.

Introduction
Tuberculosis Preventive Therapy (TPT) is a life-saving treatment to prevent latent tuberculosis (TB) infection from progressing to active tuberculosis disease. Consistent monitoring of the safety and efficacy of TPT is important to ensure tuberculosis prevention goals are achieved.

Aims
The study describes a cohort analysis of safety and efficacy assessments of Isoniazid-based TPT for persons living with HIV (PLWH) in Nigeria, to provide real-world data for informed decision-making in prevention of tuberculosis.

Methods
National HIV and tuberculosis treatment guidelines were applied in Isoniazid-based TPT for eligible PLWH receiving anti-retroviral therapy (ART) across 38 hospitals in Nigeria. A total of 10,728 PLWH (18-72 years), who commenced and completed at least one course of TPT between February 2017 and February 2022, were monitored till February 2024. Adverse drug reactions (ADRs) were evaluated for TPT safety assessments. All PLWH were clinically screened for active TB at every clinic visit, to assess the efficacy of TPT. Data were analyzed by descriptive statistics.

Results
A total of 10, 348 (96%) PLWH completed TPT without interruption while 380 (4%) PLWH interrupted TPT, re-started, and later completed TPT. Factors attributed to TPT interruption were missed clinic appointments (43%), HIV stigma (37%), and ADRs (20%). ADRs (n=76) reported included gastrointestinal disturbances (41), dizziness (17), skin rashes (10), and numbness of extremities (8). All ADRs were mild, transient, and managed according to guidelines. Active TB incidences decreased from 35% (before TPT) to 10% (after TPT). Further analysis showed that 8% of the 10% active TB incidences occurred in PLWH who completed TPT but interrupted ART due to behavioral factors.

Discussion/Conclusion
The results showed that TPT is safe and efficacious in preventing tuberculosis in PLWH. However, factors responsible for TPT and ART interruptions should be considered to ensure optimization of TPT among PLWH.

Keywords: Drug safety, Drug efficacy, Tuberculosis.

Introduction: Infective endocarditis (IE) is a rare, life-threatening bacterial infection with high morbidity and mortality, significantly affecting patients' quality of life. There is still limited data on the use of antibiotics, as well as the epidemiological characteristics of the causative pathogens in Vietnam.
Aims: The purpose of this study was to investigate the epidemiological characteristics of pathogens isolated from patients with IE, antimicrobial therapies, and the rationality of antibiotic use in the management of IE at a teaching hospital in Vietnam.
Methods: We performed a cross-sectional study on patients diagnosed with IE from January 2020 to May 2023. Data were retrospectively collected from electronic medical records. The appropriateness of antimicrobial therapies was assessed using guidelines from the European Society of Cardiology (2023), the Japanese Circulation Society (2017), and the American Heart Association (2015).
Results: A total of 84 patients were included in the study, with a median age of 57 (49- 65) years; males accounted for 63.1% of the study population. The proportion of positive blood cultures was 61.9%. Gram-positive bacteria accounted for 58.3%, with the most common pathogens isolated being Viridans group streptococci (VGS) (38.1%). The susceptibility rates of the VGS isolates to penicillin and ampicillin were 57.1% and 66.7%, respectively. Combination antibiotic regimens were more common in empirical treatment (82.9%). The overall appropriateness of antibiotic use at admission and after the susceptibility test was 62.85% and 100.0%, respectively. Fifteen patients (17.9%) developed adverse drug reactions (mostly related to vancomycin), leading to changes in antibiotic therapy. Valvular surgery (OR=4.231; 95%CI: 1.204–14.868; p=0.024) and hospital-acquired pneumonia (OR=0.148; 95%CI: 0.040–0.552; p=0.004) were factors significantly associated with the likelihood of treatment success.
Conclusion: The results of this study emphasize the importance of selecting empirical antibiotics based on updated susceptibility data and the role of valvular surgery in the treatment of IE.

Introduction: Von Hippel-Lindau (VHL) disease is a rare disease characterized by an increased prevalence of benign and malignant tumors, particularly renal cell carcinoma (RCC). There is a lack of epidemiological data for the Chinese population, and published information on the natural history of VHL disease in China is limited. Understanding the natural progression of the disease is crucial for contextualizing clinical trial results and informing further product development.

Aims: Evaluate the linear growth rate (LGR) of RCCs among VHL patients.

Methods: We conducted a retrospective, non-interventional study by reviewing medical records of VHL disease-associated RCC (VHL-RCC) patients at Peking University First Hospital from Jan-2010 to Jun-2021. Eligible patients included Chinese patients with confirmed VHL-RCCs during the study period, available follow-up, and no prior therapy or procedures for RCCs proximate to the index date. Each tumor was followed from the index date, defined as the first serial diameter measurement, to therapy or treatment impacting the tumor, or patient death or loss to follow-up. The diameter data was abstracted from the radiology reports. LGR was evaluated for RCCs with ≥3 CT/MRI measurements at tumor-level and patient-level using a multi-level linear mixed model regressing tumor diameter on time since the index date, accounting for dependency in patients and tumors.

Results: A total of 21 eligible patients with 31 tumors were included in the analysis. The median tumor diameter at the index date was 2.1 cm. The median tumor-level and patient-level LGR, derived from the multi-level model, were 0.353 cm/year and 0.401 cm/year, respectively. Almost all patients (90.5%) and tumors (96.8%) exhibited a positive LGR over the follow-up period.

Conclusion: Spontaneous regression of RCCs is unlikely for patients with VHL undergoing active surveillance in the absence of therapy. The study adds critical insights into the natural progression of the disease in a real-world setting.

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as effective maintenance therapy, offering significant survival benefits in advanced ovarian cancer (AOC).
Aim: This network meta-analysis (NMA) evaluates the comparative efficacy and safety of PARPi monotherapy as first line (1L) maintenance treatment in patients with AOC.
Methods: We searched ‘PubMed’ and ‘Embase’ platform on 10th Jan 2024 for randomized controlled trials (RCTs) of FDA approved PARPi (olaparib, niraparib, and rucaparib) in newly diagnosed AOC. Bayesian NMA was conducted using the netmeta package in R studio, version 4.3.2.
Results: We identified four RCTs with 2,046 patients. PARPi significantly improved progression free survival (PFS) in overall population as compared to placebo. For patients with BRCA-mutation (BRCAm) positive, olaparib (HR: 0.35; 95% CI: 0.26-0.47), niraparib (HR: 0.4; 95% CI: 0.27-0.59), and rucaparib (HR: 0.4; 95% CI: 0.21-0.75) significantly improved PFS compared to placebo. Similarly, for patients with homologous recombination deficiency (HRd); niraparib (HR: 0.45; 95% CI: 0.36-0.57), rucaparib (HR: 0.47; 95% CI: 0.31-0.71) significantly improved PFS, olaparib data not available in HRd. Safety analysis revealed a higher risk of grade 3 or 4 adverse events (AEs) with olaparib, rucaparib, and niraparib as compared to placebo. All assessed PARPi showed an increased risk of anemia. For neutropenia, niraparib and rucaparib exhibited significant risks, while olaparib demonstrated non-significant risk as compared to placebo. Moreover, among all assessed PARPi only niraparib showed a statistically significant risk of thrombocytopenia relative to placebo. The tolerability profile, including AE leading to dose reductions were significantly higher in all three PARPi compared to placebo. Overall risk of bias in all included RCTs was low.
Conclusion: PARPi as 1L-maintenance therapy significantly improved PFS, especially in patients with BRCAm and HRd. Although the risk of grade 3 or 4 AE was significantly higher in PARPi as compared to placebo, patients tolerated PARPi.