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Assessment of study success using conditional power (CP), the predictive power of success (PPoS) and probability of success (PoS) is becoming increasingly common for resource optimization and adaption of trials in clinical investigation. Determination of these measures is often a non-trivial mathematical task. Further, the terminologies used across the literature are not consistent, and there is no consolidated presentation on this. We have made a structured presentation on these measures for both trial success and clinical success: first, we have summarized the expressions of CP, PPoS and PoS in a general setting and subsequently, expressions for these measures are obtained for continuous, binary, and time-to-event endpoints in single-arm and two-arm trial settings. Many of these expressions are previously published; however, some of the expressions are very new including the expressions for testing median of time-to-event endpoint in a single-arm trial. We have also shown that 1 / (no. of events) consistently underestimates the variance of log(median) and alternative expression for variance was derived. Examples are given along with the comparison of CP and PPoS. Expressions presented in this paper are implemented in LongCART package in R and in R shiny app https://ppos.shinyapps.io/public/. [ABSTRACT FROM AUTHOR]

BACKGROUND: Elucidating contributors affecting liver transplant survival is paramount. Current methods offer crude global group outcomes. To refine patient-specific mortality probability estimation and to determine covariate interaction using recipient and donor data, we generated a survival tree algorithm, Recipient Survival After Orthotopic Liver Transplantation (ReSOLT), using United Network Organ Sharing (UNOS) transplant data. STUDY DESIGN: The UNOS database was queried for liver transplants in patients ≥18 years old between 2000 and 2021. Preoperative factors were evaluated with stepwise logistic regression; 43 significant factors were used in survival tree modeling. Graft survival of <7 days was excluded. The data were split into training and testing sets and further validated with 10-fold cross-validation. Survival tree pruning and model selection was achieved based on Akaike information criterion and log-likelihood values. Log-rank pairwise comparisons between subgroups and estimated survival probabilities were calculated. RESULTS: A total of 122,134 liver transplant patients were included for modeling. Multivariable logistic regression (area under the curve = 0.742, F1 = 0.822) and survival tree modeling returned 8 significant recipient survival factors: recipient age, donor age, recipient primary payment, recipient hepatitis C status, recipient diabetes, recipient functional status at registration and at transplantation, and deceased donor pulmonary infection. Twenty subgroups consisting of combinations of these factors were identified with distinct Kaplan--Meier survival curves (p < 0.001 among all by log rank test) with 5- and 10-year survival probabilities. CONCLUSIONS: Survival trees are a flexible and effective approach to understand the effects and interactions of covariates on survival. Individualized survival probability following liver transplant is possible with ReSOLT, allowing for more coherent patient and family counseling and prediction of patient outcome using both recipient and donor factors. [ABSTRACT FROM AUTHOR]

Addition of veliparib to carboplatin–paclitaxel, with continuation of veliparib monotherapy if carboplatin–paclitaxel was discontinued, improved progression-free survival (PFS) in patients with germline BRCA -associated locally advanced/metastatic HER2− breast cancer and ≤2 lines of previous cytotoxic therapy for metastatic disease in BROCADE3. A pre-planned subgroup analysis evaluated efficacy and safety in patients without previous cytotoxic therapy for metastatic disease. Patients were randomised 2:1 to receive veliparib (120 mg orally BID) or placebo on days −2 to 5. Carboplatin (AUC 6) was administered on day 1, and paclitaxel (80 mg/m2) on days 1, 8 and 15 (21-day cycles). Patients discontinuing carboplatin–paclitaxel for reasons besides progression could continue veliparib/placebo monotherapy (300 mg BID, increasing to 400 mg BID if tolerated) until progression. The primary end-point was PFS assessed by investigator. Of 509 patients in the intention-to-treat population (98.6% female; mean age 47, standard deviation 11), 413 (81%) had no previous cytotoxic therapy for metastatic disease (274, veliparib; 139, placebo). In the first-line subgroup, median PFS was 16.6 months (95% confidence interval [CI] 13.4–18.7) versus 13.1 months (95% CI 11.4–14.5) for the veliparib versus control groups (hazard ratio 0.70, 95% CI 0.54–0.89, P =.004). More patients were alive and progression-free at 2 years (36% versus 23.2%) and 3 years (27.9% versus 13.3%) in the veliparib versus control group. Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9.1%) and 8 (5.8%) patients. Veliparib with carboplatin–paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines. NCT02163694. • BROCADE3 showed veliparib plus platinum efficacy for BRCA + advanced breast cancer. • This subanalysis was in patients without prior chemotherapy for metastatic disease. • Addition of veliparib to carboplatin–paclitaxel led to durable disease control. • The data suggest a benefit of veliparib plus platinum in early lines of therapy. [ABSTRACT FROM AUTHOR]

In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody–drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis. Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m2, Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status. Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6–35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms. Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug. NCT02343406. • Clinically relevant increases in self-reported visual disorders with Depatux-M. • Similar health-related quality of life scores between Depatux-M and standard care. • Neurological deterioration-free survival was similar between treatments. [ABSTRACT FROM AUTHOR]