Background: Cancer treatment decisions are often made without specific and representative information that can inform personalized treatment. The aim of this study was to determine if we can predict, based on clinical features, which treatment regimen may maximize real-world time-to-treatment discontinuation (rwTTD) after a hormone-receptor-positive (HR+) metastatic breast cancer (MBC) patient stops responding to a first CDK4/6 inhibitor in any line. Methods: We used patient reported data (PRD) about diagnosis and treatment and medical records from 1,777 patients across the U.S. and Canada from Count Me In’s Metastatic Breast Cancer Project (MBCproject). We interviewed 17 people, academic and community based medical oncologists and MBC patients, to inform the analysis plan. Patient eligibility criteria were prior HR+ MBC diagnosis, received exactly one prior CDK4/6 inhibitor (CDK4/6) containing regimen, start date of any subsequent regimen within four months of the end date of the CDK4/6-containing regimen, and completion of MBCproject’s follow-up questionnaire at least one month after the start date of the subsequent regimen. We processed RWD from the follow-up questionnaire, performed chart review in ambiguous cases of patient eligibility, performed conformance, completeness, and plausibility verification checks to determine the dataset’s fit-for-use, and described treatment variation seen in real-world settings. We designed a new user, active-comparator cohort study with rwTTD as the continuous outcome measure, used known and hypothesized confounders to control for treatment-by-indication bias, assessed covariate balance across cohorts, and conducted Cox proportional hazards (PH) outcome regressions to identify clinically relevant associations and estimate treatment effects across regimens. The analysis plan was publicly registered with the Center for Open Science prior to performing the analysis. Results: 261 eligible HR+ MBC patients were identified, with 110 unique pairs of CDK4/6-containing and subsequent regimens. The most common CDK4/6-containing regimen was Letrozole and Palbociclib (n=98) and subsequent regimen was Capecitabine (n=63). Three mutually exclusive and clinically relevant groupings of subsequent regimens chosen for analysis were chemotherapy only (n=99), fulvestrant-containing (n=53), and everolimus-containing (n=42). Among patients in these three groups, 93.9%+ are white race, 95%+ are non-hispanic, 2.7-9.4% live in a medically underserved area, 7.1-13.1% have HR+/HER2+ MBC, mean age at subsequent treatment was 52.6-53.8 years, 17-36% had bone-only metastasis and 14.3-25.3% had liver metastasis at MBC diagnosis, median number of past treatment regimens was one, and median time on CDK4/6-containing regimen was 9-14 months. The median rwTTD was 9, 15, and 5 months in the three groups, respectively. Out of 11 covariates, nine covariates failed to reject the null hypothesis that the distribution of values are the same across the three cohorts (p>0.05). Outcome regression Cox PH revealed rwTTD hazard ratio (HR) of 2.52 [1.53-4.15; 95% confidence interval (CI)] for presence of liver metastasis, HR of 1.09 [0.63-1.89; 95% CI] for presence of bone-only metastasis, HR of 2.00 [1.20-3.33; 95% CI] for everolimus-containing regimen vs. chemotherapy only, HR of 0.85 [0.50-1.46; 95% CI] for fulvestrant-containing regimen vs. chemotherapy only, and HR of 0.82 [0.65-1.00; 95% CI] for every six months rwTTD on previous CDK4/6-containing regimen. Conclusion: In this cohort, chemotherapy was the most common treatment regimen following CDK4/6 even in second and third line settings and in patients with bone-only metastasis, which is a deviation from guideline-based treatment for many HR+ MBC patients. PRD helps develop hypotheses about patient response to treatment following CDK4/6 that can be further evaluated in larger, more diverse observational studies and clinical trials. Table 1. Characteristics of eligible patients who received chemotherapy only, everolimus containing, or fulvestrant containing regimens. Citation Format: Ariel B. Carmeli, Seth A. Wander, Mary McGillicuddy, Caroline Block, Nikhil Wagle. Real-World Time-to-Treatment Discontinuation in Hormone-Receptor-Positive Metastatic Breast Cancer Patients following CDK4/6 Inhibitor Treatment, Based on Observational Data Collected Through Patient-Partnered Research [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-02.

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Background: Colorectal cancer (CRC) remains a leading cause of cancer-related death despite being highly preventable. Efforts to increase participation in CRC screening have not met national goals. We developed a novel approach: building a business case for philanthropic investment in CRC screening. Methods: A taskforce representing the public health community, professional societies, charitable foundations, academia, and industry was assembled to: (a) quantify the impact of improving CRC screening rates; (b) identify barriers to screening; (c) estimate the "activation cost" to overcome barriers and screen one additional person;(d) develop a holistic business case that is attractive to philanthropists; and (e) launch a demonstration project. Results: We estimated that of 50 600 CRC deaths annually in the US, 55% occur in 50-to 85-year-olds and are potentially addressable by improvements in CRC screening. Barriers to screening were identified in all patient journey phases, including lack of awareness or insurance and logistical challenges in the pre-physician phase. The cost to activate one person to undergo screening was $25-175. This translated into a cost of $6000-36 000 per CRC death averted by philanthropic investment. Based on this work, the Colorectal Cancer Alliance launched the effort "March Forth" to prevent 100 000 CRC deaths in the US over 10 years, with the first pilot in Philadelphia. Conclusions: A holistic business plan can attract philanthropy to promote CRC screening. A simple message of "You can save a life from CRC with a $25 000 donation" can motivate demonstration projects in regions with high CRC rates and low screening participation.