Riaz, Irbaz Bin

6549 Background: Representation and outcomes of women, older adults, and racial minorities in ICI trials has not been previously described. Methods: MEDLINE and Embase were searched to identify ICI RCTs. Data for trial characteristics, proportion of trials reporting race, age and sex as well as the proportion of patients by race, age and sex enrolled in ICI trials was collected. Descriptive statistics were reported for trials reporting minority representation and proportion of included patients by race, age and sex. Disparities in representation were calculated using enrollment incidence disparity (EID) and enrollment incidence ratios (EIR) by comparing trial enrollment against U.S. population-based estimates acquired from the SEER 18 incidence database. The relationship of EID to key trial characteristics were compared using standard parametric and non-parametric statistical tests. Trends in EIR were analyzed using the Joinpoint Regression Analysis software. Results: 108 ICI trials from 2009 to 2020 with 48,360 patients were included in this analysis. All RCTs reported sex (101/101). 78 trials reported race (72%), of which only 41 trials (38%) reported data on all 5 U.S. racial categories (Black, White, Asian, Pacific Islander and Native American). Participation of Black patients was reported in 66 trials (61%), White participants in 78 trials (72%), Asians in 69 trials (64%), Native Americans and Pacific Islanders in 41 trials (38%), and Hispanics in 24 trials (22%). Age categories were inconsistently defined, and 80 trials (74%) reported the proportion of patient by age categories. Subgroup analyses of clinical outcomes by race, age and sex were reported in 17 (22%), 62 (79%) and 57 (73%) trials respectively. Women (trial proportion [TP]: 32%; EIR: 0.77), patients aged ≥ 65 years (TP: 42%; EIR: 0.74), Black participants (TP: 1.8%; EIR: 0.17) and Hispanic participants (TP: 5.9%; EIR: 0.67) were largely underrepresented, and Asians were overrepresented (TP: 15.9%; EIR: 2.64). Black patients were underrepresented across all cancer types. Similarly, women, older adults ( > 65 years of age) and Hispanic patients were consistently underrepresented across cancer types with few exceptions. Representation of older adults increased significantly from 2010-2020 (APC: 2.72), while representation of Black patients decreased significantly from 2009-2020 (APC: -23.37). Black patients were found to be significantly underrepresented in phase III trials (p = 0.0005), trials with OS as the primary endpoint (p = 0.004), and PD1 inhibitor trials (p = 0.002). Hispanics were significantly underrepresented in PD1 inhibitor trials (p = 0.003). Conclusions: There is both suboptimal reporting about participation and underrepresentation of women, racial minorities (particularly Black patients) and older adults in ICI trials as compared to their cancer incidence.

PURPOSE Multiple large clinical trials have investigated adjuvant tyrosine kinase inhibitors (TKIs) to reduce the risk of cancer recurrence and progression to metastasis in high-risk renal cell carcinoma. We sought to maintain living and interactive evidence on this topic, until a high level of certainty is reached for key clinical outcomes such that further updates become unnecessary and unlikely to change clinical practice. METHODS We created a living interactive evidence synthesis platform to maintain a continuously updated meta-analysis on TKI monotherapy in adjuvant renal cell carcinoma. We implemented an automated search strategy with weekly updates to identify randomized phase 2 and 3 clinical trials. Study selection, appraisal, and data extraction were done in duplicate. Cumulative meta-analysis was performed using Analyzer Module in Living Interactive Evidence platform. For each outcome (overall survival [OS], disease-free survival [DFS], and all-cause and treatment-related adverse events), we assessed certainty of evidence using GRADE approach and conducted trial sequential analysis. RESULTS This final update includes five randomized trials including recently updated data from PROTECT trial. Meta-analysis shows that adjuvant TKI monotherapy offers no benefit in OS (hazard ratio, 1.01; 95% CI, 0.91 to 1.12, high certainty) or DFS (hazard ratio, 0.92; 95% CI, 0.86 to 1.00, high certainty) and significantly increases adverse event risk. Lack of benefit was consistent across subgroups including highest-risk patients (test for subgroup differences: P = .32). Optimal information size criteria were met, and there was high certainty of evidence for lack of DFS and OS benefit for adjuvant TKIs. CONCLUSION There is no guidance on when to stop maintaining a living review. In this example, we used trial sequential analysis and high certainty of evidence (future clinical trials unlikely to change current conclusions) as a benchmark to conclude a living review in view of convincing evidence.

335 Background: Systematic reviews are outdated quickly when the evidence is rapidly evolving as the process is laborious and there is little incentive for primary author team of an index SRMA to update the evidence. Consequently, there is an epidemic of redundant SRMAs performed by different teams—sometimes with conflicted results—for treatment of first line mRCC. Methods: We have created a living, interactive systematic review (LISR)and network meta-analysis(LINMA) for the treatment of first line mRCC using an Artificial intelligence (AI) assisted framework for evidence synthesis (Living, Interactive evidence synthesis framework) (LIvE) . The framework is implemented in five-layered architecture (application layer, shared module layer, core service layer, middleware layer, and storage layer) which work together to automate the identification of new studies and analysis and semi-automate the screening and data extraction. Dynamic features such as interactive tables, figures and evidence maps are enabled using Python and JavaScript programming languages. Results: We have maintained a living, interactive evidence profile for the first line treatment mRCC since September 2019 ( LIVING WEBSITE) . Living search strategy identifies new studies as they become available. As of October 13, 2020 LISR, includes data 14 clinical trials ( PRISMA ). Baseline characteristics are summarized in an interactive table ( TABLE) . Cabozantinib& Nivolumab (Cabo-Nivo) is the highest ranked drug for improving Overall Response (OR), Progression Free Survival (PFS) and Overall Survival (OS) whereas Ipilimumab in combination with Nivolumab (Ipi-Nivo) is highest ranked drug for achieving complete response (CR). Ipi-Nivo and Atezolizumab & Bevacizumab (Ate-Bev) ranked highest and Cabo-Nivo ranked lowest for treatment related Adverse events (TRAEs). Results of network meta-analysis are summarized as interactive tables and plots ( NMA ), summary of findings tables ( MULTIPLE COMAPRISONS ) and evidence maps ( MAP ). Conclusions: LISRs can potentially reduce redundancy, increase transparency, reproducibility, enable shared-decision making (at a guideline level, or in a patient-clinician dyad) and support living guidelines.

e17539 Background: Chemotherapy with Docetaxel (D) or androgen pathway inhibition (API) with Abiraterone Acetate plus prednisone (AAP), Aplautamide(APA) and Enzalutamide(E) are acceptable, FDA approved treatment options for mCSPC. It is not clear whether the magnitude of benefit varies by the choice of initial agent [chemotherapy vs API] or by volume of disease [High vs Low]. Data is now available from all registration trials by volume status and motivated this analysis to inform initial treatment choice in mCSPC. Methods: We systematically searched MEDLINE(Ovid), Embase, and Scopus for randomized controlled trials of chemotherapy(D) or APIs (AAP, APA, ENZ) that had available hazard ratios (HRs) for overall survival (OS) and Progression Free Survival (PFS) according to patient’s volume of disease. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled overall survival HR and 95% CI by chemotherapy and APIs and by high volume(HVD) and low volume(LVD) using a random effect model, and tested for heterogeneity to assess the null hypothesis that no difference in the survival advantage exists by choice of initial agent and volume of disease. Results: Of 4456 studies identified in our search, there were 8 eligible randomized controlled trials that were included in the analysis. Both D and APIs significantly improved PFS [HR 0.48; 0.45-0.51] and OS [0.72; 0.64-0.81] when added to ADT, however the latter was associated with significantly higher improvement in PFS( P < 0.01) and OS (P = 0.03). In patients treated with D, patients with HVD derive significantly more benefit as compared to LVD( P = 0.046) and patients treated with APIs both HVD and LVD patients derive similar benefit( P = 0.80) (Table). Conclusions: mCSPC patients derive higher magnitude of survival benefit when treated with APIs as compared to D; however, D may be preferred in HVD patients. [Table: see text]

5583 Background: FDA has approved three novel AAs [Apalutamide(A), Darolutamide(D) and Enzalutamide(E)] in combination with Androgen deprivation therapy ( ADT) for treatment of (nmCRPC) patients (pts). We report the cost-effectiveness of these drugs from the US perspective to help facilitate the choice of these agents for clinical practice. Methods: A life time Markov state-transition model was constructed with three health states (Metastasis-Free Survival[MFS], Metastatic disease, and Death) to compare cost-effectiveness of AA therapies for treatment of nmCRPC based on US healthcare payer perspective. A network meta-analysis of MFS and OS was conducted due to the lack of head to head trials. An approximation of the original individual-level patient time-to-event data were derived from digitized Kaplan-Meier curves for OS and MFS. Weibull distributions was selected as the best fitted model fitted and extrapolated as per the NICE decision support unit recommendations. Medication costs were based on wholesale acquisition cost. Adverse event (AE) grades 3/4 management costs were incorporated in the model. Discount rate of 3% per year was applied to costs and effects. Life years (LYs) and quality adjusted life years (QALYs) for each treatment as well as the incremental cost effectiveness (ICER) and cost utility (ICUR) ratios were estimated. Base case analyses (BCA) and probabilistic sensitivity analyses (PSA) were estimated. Results: The table summarizes the results form BCA analyses. A+ADT offers best gain in LYs (8.37yrs) and QALYs (5.30 yrs) but at higher cost. Conclusions: Apalutamide was associated with gains in LYs and QALYs traded off with higher lifetime cost relative to other AA alternatives. ADT was associated with lower gains in LYs and QALYs traded off with lower lifetime cost relative to other alternatives. Based on a $150,000/QALY threshold pay off, A+ADT is likely more cost effective compared to E+ADT or ADT alone; while E+ ADT may be more cost effective compared to D+ ADT. [Table: see text]

2054 Background: Systematic reviews that summarize the toxicity of Immune checkpoint inhibitors (ICIs) become outdated very soon after publication. Therefore, we reported results of a toxicity meta-analysis at 2019 ASCO meeting and informed the intent to create a living systematic review (LSR). LSRs combine human and machine effort and support rapid evidence synthesis and living clinical practice guidelines. Now, we report our experience maintaining a LSR on toxicity of ICIs. Methods: Steps include quarterly literature searches to identify new clinical trials reporting ICI-associated adverse events (AEs), AI-enabled screening of new citations which meet the inclusion criteria, automated cumulative meta-analysis and an online reporting platform. Standard data formats and protocols were designed for inputting text, tables and graphics. Software was written to interpret these data and output the information in the appropriate format, such as a forest plot and summary tables. Finally, a dynamic interface that enables user inputs and displays the associated output was designed. Results: The LSR is continuously updated incorporating toxicity data from new clinical trials as it becomes available. We have screened 8000 relevant citations and summarized the odds of Grade 3 or higher AEs and AEs of special interest in patient receiving ICIs. The results are updated on quarterly basis and are available online. The results are updated on quarterly basis and will be available on a website at the time of publication. Prototype with dummy data is available at this link . This interface can also be manipulated via user input to organize and sort data tables and forest plots by type of cancer, name or mechanism (PD-1 or PD-L1) of ICI agent, single agent or combination, type of control arm, line of treatment and several other clinically relevant filters. For example, a user can instantaneously generate a meta-analysis summarizing the risk of colitis or pneumonitis in metastatic lung cancer trials with pembrolizmuab. Conclusions: This LSR engine can prospectively synthesize toxicity data from ICI trials in an efficient manner providing accurate and timely information for advanced clinical decision support at point-of-care. Efforts are ongoing to improve efficiency of screening, improve AI-enabled processes for automated screening and data abstraction, and test across multiple clinical questions.