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Background: Treatment patterns in hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− eBC continue to evolve. While AT remains the standard of care, NAT has been indicated as a viable approach to downstage higher-stage tumors. As interest in NAT trials increases, detailed data on current treatment patterns may inform future research. The objective of this retrospective observational study was to evaluate patient characteristics and treatment patterns in US patients diagnosed with HR+/HER2− eBC. Methods: This analysis included adults diagnosed with non-metastatic (stage I-III) invasive eBC between January 1, 2011, and March 1, 2019, in the nationwide Flatiron Health electronic health record–derived de-identified database. All patients had HR+/HER2− test results within 90 days of eBC diagnosis and evidence of both primary surgery and systemic treatment in the eBC setting. Patients with records of HER2-targeted treatment were excluded. NAT was defined as systemic treatment before first primary surgery; AT was defined as systemic treatment within 12 months after primary surgery among patients with ≥ 6 months of follow-up after surgery. Pathologic complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes after NAT and was subsequently confirmed at the time of primary surgery. Results: Among 4739 patients in the study, 341 (7%) received NAT (318/341 received AT following NAT) and 4398 (93%) received AT only. The proportion of patients receiving NAT increased annually from 5% in 2011 to 9% in 2018. Of NAT-treated patients, 7% achieved pCR. Patients who had higher pathology stage, higher tumor grade, younger age and who were Black or Hispanic/Latino had higher proportions of NAT (Table). Patients who received NAT were more likely to receive a mastectomy (vs lumpectomy) compared with patients who received AT only. The most common NAT regimens included chemotherapy (54%; primarily anthracycline + cyclophosphamide + taxane [ACT] regimens) or endocrine (ET) monotherapy (36%; primarily aromatase inhibitor [AI]). The most common AT regimens were ET monotherapy (79%; primarily AI or tamoxifen). Conclusions: Although AT remains the standard treatment approach in US clinical practice for HR+/HER2− eBC, interest in NAT has grown in recent years and NAT use has increased. Given the low pCR rates following NAT and since pCR is considered a surrogate marker for survival, further investigation into longer-term clinical benefits of NAT in this population is warranted as NAT may be becoming more common. Table. Characteristics of patients with HR+/HER2− eBC who received AT or NATAT only(first treatment after surgery)N = 4398NAT(first treatment before surgery)N = 341pCR achievedYesNA25 (7.3)NoNA271 (79)UnknownNA45 (13)Age at eBC diagnosisMedian (IQR), years64 (54-72)59 (49-68)RaceNon-Hispanic White2975 (68)208 (61)Non-Hispanic Black278 (6.3)31 (9.1)Non-Hispanic Asian120 (2.7)13 (3.8)Non-Hispanic other428 (9.7)27 (7.9)Hispanic/Latino282 (6.4)39 (11)Unknown315 (7.2)23 (6.7)Year of eBC diagnosis2011/20121023 (23)53 (16)2013/20141136 (26)81 (24)2015/20161129 (26)101 (30)2017/2018/201911100 (25)106 (31)Pathology group stageI2370 (54)70 (21)II1209 (27)86 (25)III282 (6.4)58 (17)Unknown537 (12)127 (37)Tumor grade11268 (29)41 (12)22297 (52)186 (55)3768 (17)111 (33)Unknown65 (1.5)3 (0.9)HistologyIDC3486 (79)267 (78)ILC615 (14)51 (15)Other/Unknown297 (6.8)23 (6.7)Primary surgery typeLumpectomy2911 (66)128 (38)Mastectomy1487 (34)213 (62)Data are n (%) unless otherwise specified.AT, adjuvant chemotherapy; eBC, early breast cancer; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; NA, not applicable, NAT, neoadjuvant chemotherapy; pCR, pathologic complete response.* The number of patients diagnosed in 2019 is very low because we only included patients diagnosed through March 2019; thus 2019 is grouped with 2017/18. Citation Format: Mary K Downer, Christopher Craggs, Preet Dhillon, Patricia Luhn, Carlos Flores-Avile, Amie Tan, Monika Patre, Frauke Schimmoller, Tanja Badovinac Crnjevic. Neoadjuvant and adjuvant therapy (NAT/AT) treatment patterns and clinical characteristics in a real-world cohort of US patients with HR+/HER2− early breast cancer (eBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-23.

Ipatasertib is a highly selective small-molecule pan-Akt inhibitor in clinical development. Ipatasertib is predominantly eliminated by the liver, and therefore the effect of hepatic impairment on ipatasertib pharmacokinetics (PK) was evaluated. In this Phase I open-label, parallel group study, the PK of ipatasertib was evaluated in subjects with hepatic impairment based on both, the Child-Pugh and the National Cancer Institute-Organ Dysfunction Working Group (NCI-ODWG) classification for hepatic impairment. A single dose of ipatasertib at 100 mg was administered and the PK was characterized in healthy subjects with normal hepatic function or mild, moderate and severe hepatic impairment. Based on Child-Pugh classification, subjects with moderate or severe hepatic impairment had an approximately 2- and 3-fold increase in systemic exposure (AUC0-∞ ) to ipatasertib, respectively, compared to subjects with normal hepatic function. Systemic exposure (AUC0-∞ ) to ipatasertib in subjects with mild hepatic impairment was comparable to that in subjects with normal hepatic function. In accordance with reduced clearance capacity, subjects with mild to severe hepatic impairment showed lower systemic exposure (AUC0-∞ ) of ipatasertib metabolite M1 (G-037720). Overall results were comparable between Child-Pugh and NCI-ODWG classification criteria. Based upon the results from this study, no dosage adjustment is required for ipatasertib when treating patients with mild hepatic impairment, whereas a dose reduction would be recommended for subjects with moderate or severe hepatic impairment. Based on real world data analysis, ∼2% of intended patient population is expected to need a modified dose due to moderate or severe hepatic impairment. This article is protected by copyright. All rights reserved.

e18795 Background: Given the rapid adoption of immune checkpoint inhibitors (CPI) in gyn cancers, we sought to characterize the real-world (RW) use of CPI, treatment patterns post-CPI, and clinical outcomes of patients (pts) with ovarian (OC) or endometrial (EC) cancer in the US. Methods: A retrospective analysis of pts with OC/EC treated with ≥1 line of systemic therapy after 1/1/2014 within the Flatiron Health (FH) real-world data (RWD) Electronic Health Record (EHR) was conducted. FH is a longitudinal EHR-derived de-identified database from ̃280 US cancer clinics. Treatment patterns after 1st CPI were identified and analyzed in pts with ≥ 6 months of observation from starting CPI per the EHR. Descriptive comparisons were performed using χ2 or t-tests, as appropriate. Time-to-next treatment (i.e., time from starting initial CPI to 1st subsequent therapy post-CPI/death) served as a PFS proxy. Pre-specified survival analyses via Kaplan-Meier methods were used for CPI therapy (i.e., 1L, 2L, 3L) and class of post-CPI therapy. Results: 7639 pts (5415 OC, 2224 EC) received ≥1 line of therapy. Median age was 65 [57-73] (OC) and 66 [60-72] (EC); 67% were white; 84% were in community practices; 34% had commercial insurance; 69% OC and 59% EC had Stage III/IV disease; 10% OC had a BRCA1/2 mutation; 12% EC were MSI-H/dMMR. 130 (2.4%) OC pts and 326 (14.7%) EC pts received CPI at any point of their cancer care. Among pts receiving CPI, CPI was given as 1st, 2nd, and ≥3rd line of therapy in 13.8%, 18.5%, 67.7% of OC pts, and 24.6%, 32.5%, 42.9% of EC pts. Median time-to-next treatment for OC pts on CPI was 5.52, 4.60, and 4.04 months in the 1L, 2L, and 3L setting, respectively (p=0.98), and for EC pts, 9.23, 6.41, and 4.27 months in the 1L, 2L, and 3L setting, respectively (p=0.05). 68 (52.3%) OC pts received subsequent therapy post-CPI; 39 (30.0%) died < 90 days post-CPI; 4 (3.1%) died > 90 days post-CPI, and 19 (14.6%) were alive with no evidence of subsequent therapy. In contrast, 110 (33.7%) of EC pts received subsequent therapy post-CPI; 98 (30.0%) died < 90 days post-CPI; 9 (2.8%) died > 90 days post-CPI, and 105 (32.2%) were alive with no evidence of subsequent therapy. Of 68 OC pts who received subsequent therapy after CPI, 38.2% received chemo only, 25.0% additional CPI (alone or in combo), 16.2% targeted therapy, and 14.7% chemo + bevacizumab. Of 110 EC pts who received subsequent therapy, 38.2% received chemo only, 29.1% additional CPI (alone or in combo), 20.0% targeted therapy, and 6.4% chemo + bevacizumab. Conclusions: Checkpoint inhibitors were used in later lines of therapy more notably in OC than EC. Time-to-next treatment on CPI did not seem to vary by line of therapy among OC pts, whereas time-to-next treatment on CPI appeared longer when CPI was used earlier among EC pts. This study reveals early observations into the RW use and sequencing of checkpoint inhibitors in ovarian and endometrial cancers.

Genomic testing is an important part of personalized oncology. This study explored testing patterns and results, as well as patient (pt) characteristics, in the BC setting. Data from the nationwide, de-identified Flatiron Health (FH)-Foundation Medicine, Inc. (FMI) BC clinico-genomic database were included; pts had to have been treated in a FH network oncology practice and tested with a FMI CGP test. Pts were >18 years old and had a primary or metastatic BC (mBC) diagnosis between 1/1/2011 and 3/30/2020. Only pts with solid-tumor tissue of origin and solid-tumor assay tests were considered; pts whose tests occurred >120 days after their last visit (based on report date) were excluded. Pt cohorts were classified by timing of test result receipt: cohort 1, between primary diagnosis and 120 days post-diagnosis if no surgery recorded; cohort 3a, within 60 days prior to/after mBC diagnosis; and cohort 3b, >60 days after mBC diagnosis. Pt characteristics and actionable mutations according to the FMI report only (associated with sensitivity or resistance to ≥1 therapy) were described by cohort and BC subtype, defined at primary diagnosis for cohorts 1/2 and at mBC diagnosis for cohorts 3a/3b. Pt characteristics were compared with those of the FH cohort (not tested with next-generation sequencing or received other next-generation sequencing tests). Overall, 4183 pts were included: 285 in cohort 1, 412 in cohort 2, and 3486 in cohorts 3a/3b. There was an overrepresentation of triple-negative BC (TNBC) among pts tested in the early setting (cohorts 1/2) vs the underlying population (33%/32% vs 10%), and an underrepresentation of hormone receptor (HR)-positive/HER2-negative BC (45%/48% vs 71%). TNBC remained overrepresented among pts tested at mBC diagnosis (cohort 3a; 30% vs 11%), but not during mBC follow-up (cohort 3b; 14% vs 11%), which followed the underlying FH distribution. The majority of patients were tested using samples collected within their respective test windows: 100% in cohort 1, 63% in cohort 2, and 78% and 46% in cohorts 3a/3b. For pts tested in the mBC setting, 22% and 15% in cohorts 3a and 3b, respectively, were tested using tissue collected >60 days prior to mBC diagnosis. Percentages of pts with at least one FMI-report-actionable alteration ranged from 94% (n = 601) in HER2-positive samples to 75% (n = 668) in pts with TNBC. Among this BC cohort, FMI-CGP predominantly occurred in the mBC setting, and use of archival tissue for CGP occurred in later lines of treatment. Testing, in particular prior to mBC diagnosis, reflected a disproportionately higher prevalence of pts with TNBC, potentially due to there being fewer satisfactory treatment options in this setting. The distribution of actionable alterations varied by HER2 and HR status. Citation Format: Achim Rody, Nayan Chaudhary, Christopher Craggs, Marcio Debiasi, Gilles Erb, Virginia Fisher, Margaret McCusker, Tamara Snow, Maria Vidal Losada, Patricia Luhn. Comprehensive genomic profiling (CGP) in breast cancer (BC): Patterns and results from a clinico-genomic database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 437.

58 Background: It is estimated that more than 40% of patients with mCRPC have functional loss of phosphatase and tensin homolog (PTEN) tumor suppressor gene, which is associated with unfavorable prognosis and reduced response to androgen receptor-targeting therapy. We describe patient characteristics and survival outcomes by PTEN LOF status among patients with mCRPC in real-world clinical practice. Methods: We conducted a retrospective cohort study using data from the nationwide Flatiron Health-Foundation Medicine mCRPC Clinico-Genomic database (FH-FMI CGDB), a de-identified database linking data derived from electronic health records with genomic data derived from FMI comprehensive genomic profiling (CGP) tests. The study included patients ≥18 years old, with a primary diagnosis of mCRPC between 1/1/2013 and 6/30/2019 who underwent FMI CGP testing and who had a valid PTEN LOF status. Patients were included if their PTEN report date and mCRPC diagnosis date occurred before death or censoring. PTEN LOF status was identified via FMI’s CGP testing. Kaplan-Meier (KM) methods assessed overall survival (OS) by PTEN LOF status from the date of mCRPC diagnosis (later of metastasis and castration resistance) until death or end of study follow-up. A stratified Cox regression model was used to estimate the hazard of death. The Cox model was adjusted for age, race and sequence of metastasis/CRPC diagnoses, and was stratified by the year of mCRPC diagnosis. Adjustments to account for left-truncation and survivorship bias were made in the KM analysis and the Cox regression model. Results: Among the 458 patients who met the eligibility criteria, 174 (38%) had PTEN LOF. The majority of the study sample (76%) was diagnosed with castration-resistance after metastasis. The PTEN LOF group had a higher percentage of white patients (80% vs. 68%; p= 0.01) compared to the PTEN non-LOF group. The mean age of the study sample was 68 years, and there was no difference in mean age at diagnosis by PTEN LOF status ( p= 0.17). Based on the KM estimates adjusted for left-truncation, the median OS was 14.3 months (95% confidence interval [CI]: 11.1-19.7) in the PTEN LOF group compared to 18.3 months (95%CI: 15.5-21.5) in the PTEN non-LOF group (log-rank p= 0.049). In the multivariable Cox model, the PTEN LOF group had numerically 30% higher risk of death compared to the PTEN non-LOF group (hazard ratio = 1.30; 95% CI: 0.99-1.71; p= 0.057). Conclusions: Among real-world patients with mCRPC in the CGDB, PTEN LOF could be associated with poorer survival outcomes, potentially highlighting the unmet need among these patients. Additional studies with larger cohorts are needed to better evaluate the survival outcomes of patients with PTEN LOF. Therapeutic agents acting on the PTEN/PI3K/AKT/mTOR pathway are being tested in clinical trials, and could potentially improve outcomes in this subgroup of patients with mCRPC.

e13103 Background: In March 2019, atezo + nab-pac received accelerated FDA-approval for the treatment (tx) of patients (pts) with unresectable locally advanced or metastatic TNBC who express PD-L1 in immune cells (IC), based on the results from the randomized IMpassion130 clinical trial. A companion diagnostic, the Ventana SP142 PD-L1 assay, was concurrently approved. This real-world data analysis describes the uptake of both PD-L1 testing and therapy with atezo + nab-pac from the time of approval. Methods: This is a retrospective study using the Flatiron Health electronic health record (EHR) derived de-identified database, representing > 2.4 million US cancer pts from > 280 cancer clinics. Pts diagnosed with mTNBC starting any line of systemic therapy between March 9, 2019 and December 31, 2019 (to be updated in April 2020 for 12-months follow-up) were included. Two cohorts were examined: pts receiving either atezo-based tx, or tx without atezo. Demographics were described in the pt group overall and by line of therapy (LOT). Steroid tx at baseline was classified as any order/administration of a steroid within the first three administrations of a systemic therapy in a given LOT. Any record of a PD-L1 test was reported. Results: 228 pts diagnosed with mTNBC were included; 65 pts (28%) received any atezo combination, the majority in combination with nab-pac: 57% (n = 37) in first-line (1L), 25% (n = 16) in second-line (2L), and 18% (n = 12) in third-line or later (3L+). Median age at metastatic diagnosis (mDx) for atezo-treated pts was: 1L, 65 y (IQR: 49, 72); 2L, 56 y (IQR: 48, 64); 3L+, 52 y (IQR: 42, 60). Median age at mDx for non-atezo-treated patients was: 1L, 63 y (IQR: 53, 74); 2L, 59 y (IQR: 51, 65); 3L+, 61 y (IQR: 53, 71). Of 228 pts, 158 (69%) had any PD-L1 test recorded. Among atezo-treated pts, 62 (95%) had a documented PD-L1 test; of those 40 (62%) were tested using the SP142 assay. Overall, 205 tests were recorded: SP142, n = 96 (46.8%); unknown/not documented, n = 44 (21.5%); 22C3, n = 36 (17.6%); lab-developed test, n = 26 (12.7%); SP263, n = 2 (1.0%); and 28-8, n = 1, (0.5%). 37 (57%) atezo-treated pts received a steroid at baseline. Conclusions: Atezo tx and testing with SP142 is being implemented following accelerated FDA-approval. A considerable proportion of pts received steroids at baseline and had nab-pac as chemotherapy backbone in clinical practice. Clinical outcomes of atezo-treated pts in the real-world setting remain to be further explored pending longer pt follow-up times.

We investigated whether physical activity (PA) correlates differed for 9–10 year-old British children living in urban, suburban and rural settings. We analysed cross-sectional data on 1653 children (SPEEDY study). Exposure variables were self-reported, whilst PA was measured using Actigraph accelerometers. Data were analysed using multilevel hierarchical regression models, stratified by home setting. PA levels did not differ by home setting. Boys, those of normal weight and those having a preference for PA had higher PA levels in all strata, but additional correlates were identified within each setting. These results highlight the potential importance of tailoring interventions to specific environmental and population strata.

Context Data are available on correlates of physical activity in children and adolescents, less is known about the determinants of change. This review aims to systematically review the published evidence regarding determinants of change in physical activity in children and adolescents. Evidence acquisition Prospective quantitative studies investigating change in physical activity in children and adolescents aged 4–18 years were identified from seven databases (to November 2010): PubMed, SCOPUS, PsycINFO, Ovid MEDLINE, SPORTDdiscus, Embase, and Web of Knowledge. Study inclusion, quality assessment, and data extraction were independently validated by two researchers. Semi-quantitative results were stratified by age (4–9 years, 10–13 years, and 14–18 years). Evidence synthesis Of the 46 studies that were included, 31 used self-reported physical activity; average methodologic quality was 3.2 (SD=1.2), scored 0–5. Of 62 potential determinants identified, 30 were studied more than three times and 14 reported consistent findings (66% of the reported associations were in the same direction). For children aged 4–9 years, girls reported larger declines than boys. Among those aged 10–13 years, higher levels of previous physical activity and self-efficacy resulted in smaller declines. Among adolescents (aged 14–18 years), higher perceived behavioral control, support for physical activity, and self-efficacy were associated with smaller declines in physical activity. Conclusions Few of the variables studied were consistently associated with changes in physical activity, although some were similar to those identified in cross-sectional studies. The heterogeneity in study samples, exposure and outcome variables, and the reliance on self-reported physical activity limit conclusions and highlight the need for further research to inform development and targeting of interventions.

Background Predictors of physical activity (PA) change are rarely investigated separately for different PA intensities and for weekdays/weekends. We investigated whether individual-level predictors of one-year change in objectively-measured physical activity differ for moderate PA (MPA) and vigorous PA (VPA) and for weekends and weekdays. Methods Accelerometer-assessed PA (mins) was obtained at baseline and +1 year (n = 875, 41.5% male, Mean ± SD baseline age: 9.8 ± 0.4 years-old). Potential predictors (n = 38) were assessed at baseline from psychological (e.g. self-efficacy), socio-cultural (e.g. parent support) and environmental domains (e.g. land use). Associations between predictors and change in MPA (2000–3999 counts/minute (cpm)) and VPA (≥4000 cpm) separately for weekdays and weekends were studied using multi-level linear regression. Analyses were adjusted for school clustering, sex and baseline PA. Results Weekend PA declined (MPA decline 4.6 ± 21.8 mins/day; VPA decline: 2.1 ± 20.1 mins/day; both p