Sites Of Mets Research Articles

Exploratory Analysis Of Epidemiological, Clinicopathological Characteristics And Prognostic Factors Of Stage IV Epithelial Ovarian Cancers: A Single Institutional Study In Chennai

Background: Ovarian cancer (oc) is the 3rd most common cancer (ca) in females in India (globocan 2020)1 , epithelial ovarian cancer consists of 90% of all oc. More than 70% of ovarian ca patients diagnosed at advanced stage due to its asymptomatic nature and insidious onset of the disease. Metastases(mets) remained a major cause of mortality in ovarian cancer patients. This study is being undertaken to identify prognostic and predictive factors associated with the survival of patients with metastatic ovarian cancer. Materials and methods: It is a retrospective study. Patients diagnosed with stage IV epithelial ovarian cancer (treatment naive), who attended the department of medical oncology, Govt Royapettah Hospital (GRH), Chennai during 2013- 2018 with regular follow up included. 5 years follow-up data collected till dec, 2023. Aim of this study is to identify the epidemiological, clinicopathological characteristics, treatment outcome and other prognostic factors predicting overall survival (os) and progression free survival (pfs) in patients with stage IV ovarian cancer. Results: In this study 85 patients with stage IV epithelial ovarian ca were analysed. In our study median os is 27 months, pfs is 13 months. Overall survival (os) rate at 2 years (yr)= 0.5647, overall survival (os) rate at 5 years = 0.105. Progression free survival (pfs) rate at 2 years = 0.1765, progression free survival (pfs) rate at 5 years = 0.0471. Kaplan Meier (KM) survival curves have shown response after 1 st line treatment, surgery vs no surgery, platinum sensitive recurrence have significant association with 2 year, 5 year os and pfs (p<0.05). Hpe (high grade serous vs less common ovarian cancers) has showed significant correlation with 5 year survival (p<0.05), univariate cox regression analysis has shown, number of mets (single site vs multiple site) significantly associated with improved 2 year survival (p=0.02) and pfs (p=0.005). Both univariate and multivariate analysis showed age (<=56 vs>56) as independent factor correlating with 5 year survival (p=0.02), (p=0.01), multivariate cox regression analysis showed pretreatment ca 125 is an independent variables for pfs (p=0.04). Conclusion: In our study KM survival curves have shown if patients could undergo cytoreductive surgery, had response after 1 st line treatment (surgery and chemo) , significant improvement in 2 year, 5 year os and pfs can be achieved, though not established in regression analysis. Recurrence rate remained very high in advanced stage, in our study KM survival curve has shown platinum sensitive recurrence has significantly better 2 year, 5 year os and pfs rate. Cox regression analysis showed patients with single site of mets have significantly better 2 year survival and pfs than patients with multiple site of mets. Pre treatment raised ca 125 found to be an independent factor which can predict poor pfs. Higher age is an independent factor found to impact 5 year os

Differences in genomic, transcriptomic, and immune landscape of prostate cancer (PCa) based on site of metastasis (mets).

21 Background: In patients with metastatic PCa, specific sites of mets are associated with differential overall survival, with lymph node (LN) only disease having the best survival, followed by bone, lung, and liver, with each showing progressively worse survival. However, the biology of tropism to specific sites and differential outcomes has not been fully explored. Herein, utilizing a large, multi-institutional, real-world dataset, we hypothesized that differences in molecular and immune landscape of PCa based on site of mets may explain different clinical outcomes. Methods: DNA (592-gene panel or whole exome) and RNA (whole transcriptome) sequencing was performed for primary PCa (PPCa) and unpaired PCa mets sites (non-visceral: NV and visceral: V) and sequenced at Caris Life Sciences (Phoenix, AZ). Mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) was tested by IHC/NGS, respectively. Tumor mutational burden (TMB) (high >10 mut/Mb) was assessed. Androgen receptor (AR) signaling score and Neuroendocrine Prostate Cancer (NEPC) score were calculated using previously defined RNA-based signatures. Pathway enrichment was determined by Gene Set Enrichment Analysis (GSEA). Immune cell fractions calculated by deconvolution of WTS using quanTIseq. Statistical significance was determined by chi-square and Mann-Whitney U tests. All analyses done with CODEai. Results: 6074 PCa samples, including 3411 PPCa, 1634 NV (bone = 784, LN = 850) and 1029 V (liver: 468, lung: 177, bladder: 241, other: 143) were evaluated. Age at sample collection ranged 30 to 70+ years. Compared to PPCa, significantly higher mutation rates were observed for multiple genes in V (RB1 8% vs 3%, TP53 43% vs 31%, PTEN 12 % vs 8%, CTNNB1 8% vs 3%, AR 13% vs 1%, APC 15% vs 5%, AKT1 4% vs 2%; p<0.05 for all) and NV mets (AR 9% vs 1%, SPOP 7% vs 10%, TP53 38% vs 31%, CTNNB1 6% vs 3%, and KMT2C 8 % vs 5%; p<0.05 for all). Alterations of RB1, APC and AR were more frequent, and SPOP less common in liver mets compared to PPCa, while SPOP, KRAS, PIK3CA, APC and BAP1 mutations were more common in lung mets (p < 0.05 for all). Compared to PPCa, V and NV mets had higher AR signaling and interferon-γ scores, while V mets had higher NEPC scores and were more frequently PD-L1+ (SP142) and TMB-high (p<0.05 for all). No differences in dMMR/MSI-H was observed between PPCa, V and NV mets. AR-V7 variant prevalence was significantly higher in V (36%) and NV (33%) mets compared to PPCa (7%, p-value < 0.05). GSEA identified E2F, G2M checkpoint and MYC target pathways as being more upregulated in both V and NV mets compared to PPCa (q<0.05). Compared to PPCa, V and NV mets were significantly less enriched in macrophage M2, NK cells and Tregs, while V mets were also less enriched in B cells and neutrophils (p<0.05). Conclusions: We elucidate molecular and immunologic mechanisms of metastatic tropism in advanced PCa. These data may facilitate future drug development.

Bone metastasis in patients with germ-cell tumors: Analysis of survival outcomes and prognostic factors.

e17029 Background: Bone metastasis (BM) is uncommon in patients with germ-cell tumor (GCT). There is lack of data regarding optimal treatment approach. We report the outcomes and prognostic factors in 99 pts with BM treated at our institution. Methods: We identified 99 pts with GCT and BM treated at Indiana University between year 1986-2021. Kaplan-Meier methods were used for progression free survival (PFS) and overall survival (OS) analysis. Results: Median age was 31.5 (range, 13.1-58.8). Primary tumor histology was non-seminoma in 77 and pure seminoma in 22. Predominant histology was seminoma in 26, yolk sac tumor 23, mixed 16, embryonal ca 12, teratoma 10, choriocarcinoma 9. Other mets sites included lungs in 68, RP LNs in 63, liver in 34, brain in 19. BM location was spine in 73, pelvic bones in 22, humerus/femur in 14, ribs in 10, sternum/clavicle in 7. Median pre-chemo AFP was 438 (range, 1-75,414) and hCG 80 (range, 0.7-1,700,000). 1L chemo was BEP x4 in 46, VIPx4 in 10, BEP x3 + EP x1 in 8, EP x4 in 8, BEP x3 in 7, VIPx3 in 1, and other in 19. Histology of BM resection for those who underwent surgery was viable non-teratoma GCT in 6, teratoma in 1, malignant transformation of teratoma in 3, and necrosis in 3. 28 had radiotherapy to symptomatic BM. 80 (82.5%) pts progressed after 1L chemo and 46 (53.5%) progressed after 2L chemo. With median f/u from diagnosis of 5.7 years, 5 yr PFS was 17.8% (95% CI 10.3-27.0) and 5 yr OS was 59.9% (95% CI 47.9-70.0). For pts with pure seminoma, 5 yr PFS was 29.8% (95% CI 12.4-49.5) and 5 yr OS 83.1% (95% CI 55.7-94.3). For non-seminoma: 5 yr PFS was 14.6% (95% CI 6.9-25.1) and 5 yr OS 52.2% (95% CI 38.4-64.2). Multivariable analysis indicated that pts with concurrent liver and/or brain mets had worse OS. Conclusions: Outcomes of pts with GCT and BM are inferior than what is expected based on IGCCCG risk categories. Pts with concurrent liver and/or brain mets have particularly worse OS outcomes. [Table: see text]

Abstract P1-11-04: Assessing the clinico-pathological characteristics of HER2 positive metastatic breast cancer patients experiencing radiologic complete response in a nationwide cohort

Abstract Background: Up to 6% of patients (pts) with HER2 positive (pos) metastatic breast cancer (MBC) experience a radiologic complete response (rCR) to a first line of therapy, but these results mostly derive from dated and/or limited cohorts. Aim of this study was to define the clinico-pathological characteristics of HER2 positive (pos) MBC pts experiencing a rCR. Methods: Pts were selected from the database of the GIM14 study (NCT02284581) and classified according to the best radiologic response obtained to the first line chemotherapy (CT) and upon time-to-treatment-failure (TTF). rCR was defined as complete response (CR) with a TTF > 3 months. The association across variables was tested through logistic regression and their prognostic impact in terms of overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 3,423 pts included in the GIM14 study, 814 had HER2 pos MBC. After exclusion of pts treated with first line endocrine therapy and/or with TTF < 3 months, 656 pts were included in the present analysis, of which 96 (14.6%) experienced a rCR. Instead, the best response was a partial response for 295 pts (45.0%), stable disease for 221 pts (33.7%), and progression for 44 pts (6.7%). Most pts (59.8%) presented de novo MBC; 379 pts (57.8%) had visceral metastases (mets), 609 pts (92.8%) did not have central nervous system (CNS) involvement and 318 pts (48.5%) had only 1 site of distant mets. Also, 445 pts (67.9%) had hormone receptor (HR) pos disease, a HER2 3+ score at immunohistochemistry (IHC) was present in 59.8% of cases versus 40.2% with HER2 2+ at IHC and in situ hybridization (ISH) + disease. Taxanes were the main CT backbone (489 pts, 74.5%), 341 pts (52.0%) had received a Trastuzumab-Pertuzumab doublet. At multivariable analysis, higher odds of experiencing a rCR were reported for presence of non-visceral mets (OR 1.87, 95%CI 1.10-3.17), low number of metastatic sites (OR 2.42, 95%CI 0.80-7.33 for 1 site only) and HER2 3+ score at IHC (OR 1.80, 95%CI 1.09-2.98). Disease-free interval (DFI) was associated to rCR at univariable but not at multivariable analysis. HR status, CT backbone and type of anti-HER2 regimen were not associated with rCR neither at univariable nor at multivariable analysis. Median follow-up was 76.2 months. Amongst pts with TTF>12 months, those with rCR had a significantly higher OS compared to those not experiencing a rCR (median OS 133 and 90 months, respectively; p=0.0191). OS rates in pts with TTF ≥ 12 months were 97.8% at 2-year follow-up and 59.4% at 5-year follow-up. Instead, in pts with TTF ≥ 60 months, OS rates were 76.7% at 10-year follow-up. Amongst the 96 pts experiencing a CR, 38 had a rCR with TTF between 12 and 60 months, while 22 pts had a rCR with a TTF ≥ 60 months. The remaining pts had a CR with a TTF < 12 months. Pts with HR negative (neg) disease were found to be more likely to experience a rCR with a with TTF between 12 and 60 months, whilst pts with HR pos disease had a higher probability to experience a rCR with a TTF ≥ 60 months (p=0.0074). Pts with HER2 3+ score at IHC had a higher probability to achieve a rCR with a TTF ≥ 12 months compared to pts with HER2 2+ score at IHC and ISH + (p=0.0216). Age at diagnosis, menopausal status, DFI, number and site of mets, CT backbone and anti-HER2 therapy did not influence the duration of the rCR obtained. Conclusions: This study characterized a real-world cohort of HER2 positive MBC patients experiencing radiologic complete response to a first line treatment. Based on these results a clinical trial focused on liquid biopsy-based minimal residual disease is being designed. Novel anti-HER2 agents are gaining momentum as ever increasingly effective treatments and future de-escalation strategies after complete response will represent a growing need. Citation Format: Linda Cucciniello, Eva Blondeaux, Claudia Bighin, Simona Gasparro, Stefania Russo, Arianna Dri, Palma Pugliese, Andrea Fontana, Giuseppe Naso, Antonella Ferzi, Ferdinando Riccardi, Valentina Sini, Luca Boni, Alessandra Fabi, Filippo Montemurro, Michelino De Laurentiis, Grazia Arpino, Lucia Del Mastro, Lorenzo Gerratana, Fabio Puglisi. Assessing the clinico-pathological characteristics of HER2 positive metastatic breast cancer patients experiencing radiologic complete response in a nationwide cohort [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 P1-11-04.

Real world (rw) racial differences in treatment (tx) patterns and clinical outcomes among patients (pts) with mCRPC.

95 Background: Contemporary rw data is needed to describe the heterogeneity of the tx landscape among diverse pt populations. This study assessed rw tx patterns and clinical outcomes among US pts receiving tx for mCRPC. Methods: Data from pts with mCRPC initiating first line (1L) tx between 2016 and 2019 were abstracted from medical charts. Clinical characteristics and tx patterns stratified by race (White [W], Black [B], and Other [O]) were compared using descriptive statistics. Rw progression-free survival (rwPFS) and overall survival (OS) were analyzed using Kaplan–Meier method. A multivariate Cox model explored associations between race and rwPFS/OS, controlling for confounders. Results: 122 physicians contributed data from 260 charts (W n=127, B n=81, O n=52 pts). The median age was 69 years; 64 (25%) had ECOG score ≥2. Common sites of metastases (mets) were bone (73%) and lymph nodes (34%); median Gleason score (GS) was 8.0, with no significant differences in sites of mets or GS among B and W pts. Most common txs prior to mCRPC included androgen deprivation therapy (ADT) monotherapy (39%), chemotherapy (CT; 15%), and novel hormonal therapy (NHT; 9%). Prior to mCRPC, more B pts were offered tx intensification with NHTs or CT compared with W pts (35% vs 14%). NHT was the most common 1L mCRPC therapy, followed by CT (Table). Compared with W pts, more B pts were offered NHT (65% vs 59%, P=0.44) and CT (26% vs 20%, P=0.38) in the 1L setting. Adjusted median rwPFS on 1L tx was 43.7 months (mo; 95% CI: 27–not estimable [NE]). A longer rwPFS was observed for B vs W pts; median rwPFS NE (95% CI: 34.7–NE) vs 34.7 mo (95% CI: 21.0–NE), hazard ratio (HR)=0.58 (95% CI: 0.35–0.97; P<0.05). B pts had numerically greater OS vs W pts, HR=0.58 (95% CI: 0.31–1.1; P=0.09). Conclusions: In this rw study of pts receiving 1L tx for mCRPC, rwPFS was better compared with clinical trial data, particularly among B pts, who were more likely to receive life-prolonging txs in the 1L setting. These data suggest B pts might respond better to systemic therapies compared with W pts, and disparities observed in other settings may be attributed to access barriers. [Table: see text]

VEGF inhibitors (VEGFi) activity in liver metastases (mets) regardless of primary cancer type: Meta-analysis and systematic review.

3024 Background: Liver metastasis is a poor prognostic factor in several cancers and is associated with poor response to immunotherapy (IO) in melanoma and lung cancer. VEGFi have activity in hepatocarcinoma (HCC) and is hypothesized to be due the hypoxic microenvironment. Whether this is also true for liver mets is unknown. We sought to assess the efficacy of VEGFi in liver mets utilizing randomized-controlled clinical trials (RCTs) testing the efficacy of VEGFi, regardless of primary cancer site. Methods: Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to January 1, 2022. All RCTs that compared a backbone of systemic therapy (chemotherapy [chemo] and/or IO and/or targeted therapy [TT]) or best supportive care (BSC) with vs without VEGFi in patients (pts) with liver mets from any cancer were selected. HCC trials were excluded. Study design, cancer type, number of pts, lines of treatment, study drugs and hazard ratios (HRs) with 95% CIs for overall survival (OS) and progression-free survival (PFS) were extracted. Pooled effects of VEGFi in pts with liver mets across different cancer types were estimated using random effect model with inverse variance. Heterogeneity between studies was assessed by I2 statistics. Sensitivity analyses were performed considering prespecified subgroups of trials. Results: 3170 pts with liver mets from 19 RCTs were included in this meta-analysis: 8 colorectal cancer, 4 non-small cell lung cancer, 4 renal cell cancer & urothelial cancer, 1 pancreatic cancer, 1 GIST and 1 gastric cancer. Backbone systemic therapy in these trials included: chemo (11), TT (2), IO (2), chemo+IO (1), chemo+TT (1); and 2 BSC trials. Moderate heterogeneity between studies for both PFS (I2= 55%) and OS (I2= 46%) was seen. The addition of VEGFi to standard systemic therapy or BSC was associated with superior PFS (HR = 0.61; 95% CI, 0.50-0.74; p < 0.0001) and OS (HR = 0.86; 95%CI, 0.76-0.99; p = 0.0334) in pts with liver mets, regardless of whether pts had only liver mets or concurrent other sites of mets. In the subset of RCTs with data on pts without liver mets, the benefit with VEGFi was more pronounced in patients with liver mets (HR = 0.56) vs those without liver mets (HR = 0.64) for PFS, but not for OS. Conclusions: The addition of VEGFi to standard management improved survival outcomes in pts with liver mets across different cancer types and warrants further investigation. VEGFi added to IO may be effective in pts with resistant liver mets.

Impact of site-specific metastases and clinical complications on outcomes of patients with metastatic renal cell carcinoma (mRCC).

e16527 Background: Prognostic models based on the heterogeneity of mRCC disease characteristics, including anemia, hypercalcemia, and neutrophilia, are routinely used in clinic. In an attempt to improve these models, we conducted a retrospective analysis of patients(pts) with mRCC to assess the association of overall outcomes with specific sites of metastasis (mets) and clinical complications. Methods: We extracted data from the SEER-Medicare database on pts diagnosed with RCC from 2004 to 2015. Study cohorts included patients who were > 65 years old and had at least 1 of following site-specific mets or complications: ascites, bone mets, brain mets, liver mets, lung mets, pancreatic mets, and hypercalcemia. To accurately delineate the relationship between site-specific/clinical complications and clinical outcomes, pts were stratified into 3 groups by the timing of site-specific mets and complications appearance : A1 (pts with a site-specific mets or complication at the initial diagnosis of mRCC); A2 (pts with a site-specific mets or complication any time after diagnosis of mRCC); and B (pts who have no site-specific mets or complication but have other mets or complications). Kaplan-Meier curves for overall survival(OS) were produced and median(m) OS were reported. Multivariable Cox modeling was performed to assess the association of individual mets or complications with OS between pre-specified subgroups(A1+A2 vs B, A1 vs A2+B and A1 vs B). Results: We identified 4640 RCC pts in the SEER-Medicare database who had at least 1 of the specified sites of mets or complications. At a median follow-up of 8 months(mons), ascites, brain mets and hypercalcemia were associated with worse mOS in all predefined subgroup analysis. In pts with liver mets, groups A1+A2 had shorter OS than B . In pts with lung mets, mOS in A1 was longer than in A2+B or B. bone mets did not show a statistically significant correlation with OS in any stratified analysis. Lastly, pancreatic mets was associated with longer mOS, but this did not reach statistical significance regardless of the comparison groups (table 1). Conclusions: Our data show that ascites, brain mets, hypercalcemia, and liver mets was associated with poor prognosis, and de novo lung mets was associated with better clinical outcome in patients with mRCC. Based on these findings, we are working on comparing the clinical outcome of mRCC pts treated with targeted therapy to that of pts treated with immunotherapy and building a new prognostic model.[Table: see text]

First-line (L1) therapy targeting EGFR in lung metastases (mets) of colorectal cancer (mCRC): An ARCAD pooled analysis.

3578 Background: Monoclonal antibodies (mab) targeting EGFR are recommended in L1 treatment (trt) for mCRC in patients (pts) with RAS wild-type (WT) tumor and primary left CRC. ARCAD database contains individual data of randomized trials that evaluated anti-EGFR mab plus chemotherapy (CT). In this analysis we aimed to evaluate anti-EGFR benefit in mCRC with lung mets, either as single site or multiple sites. Methods: Individual pts data from four trials (PRIME, CRYSTAL, COIN, OPUS) comparing CT +/- anti-EGFR were pooled. KRAS status was not required at inclusion to these studies. The primary endpoint, overall survival (OS), was estimated using Kaplan-Meier method, prognostic value of lung mets was evaluated by stratified Cox models in pts groups defined by KRAS status. The predictive value was evaluated by interaction test (Int) between trt and lung mets status in pts group defined by KRAS status and considered as significant with a P < 0.1. Results: 3681 pts with known KRAS status were included, 2171 WT and 1510 mutant (MT). Pts characteristics were well balanced. Significant median OS benefit of anti-EGFR was observed in the whole KRAS WT population and in the left colon and rectum subgroup but not in the right colon subgroup. In pts with KRAS WT single site mets, a non-significant benefit of anti-EGFR was observed only among pts without lung mets (N = 642). In pts with lung single site mets (N = 129), a significant benefit ( P= 0.018) in the KRAS MT population (N = 55) was observed, but Int was non-significant ( P =0.157). In pts with KRAS WT and multiple without lung mets sites (N = 673), no benefit of anti-EGFR was observed and Int was significant ( P= 0.054). Pts with KRAS MT multiple sites with (N = 656) or without (N = 397) lung mets, had no benefit of anti-EGFR. The same findings were found in the left primary pts and in the two fluoropyrimidine backbone. PFS analyses confirm the OS results. Conclusions: In this ARCAD analysis pts with lung mets as a single site appear to benefit from anti-EGFR L1 therapy in case of KRAS MT. This unexpected result based on a limited sample size cannot be explained on the knowledge of anti-EGFR therapy. Furthermore, pts with multiple mets sites have a benefit of anti-EGFR therapy only in the presence of lung mets even in KRAS WT left primary tumor. These findings need further confirmation and may initiate the search for a specific molecular phenotype associated with lung mets in CRC pts. [Table: see text]

Abstract P3-13-04: Clinical features and genetic alterations in patients (pts) with HER2-positive breast cancer (BC) and central nervous system (CNS) metastases (mets) in the real world

Abstract P3-13-04: Clinical features and genetic alterations in patients (pts) with HER2-positive breast cancer (BC) and central nervous system (CNS) metastases (mets) in the real world

Nivolumab plus cabozantinib (N+C) versus sunitinib (S) for advanced renal cell carcinoma (aRCC): Outcomes by baseline disease characteristics in the phase 3 CheckMate 9ER trial.

4553 Background: First-line N+C significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in aRCC patients (pts) in the phase 3 CheckMate 9ER trial, leading to FDA approval of N+C in this setting. A deeper understanding of how baseline disease characteristics may impact clinical outcomes with N+C vs S may inform clinical decision making. Methods: Pts with clear cell aRCC were randomized to N 240 mg IV Q2W + C 40 mg PO QD vs S 50 mg PO QD (4 weeks of 6-week cycles). In this post hoc exploratory analysis, PFS, OS, and ORR were evaluated across pt subgroups defined by baseline IMDC risk status, organ sites of metastases (mets), number of organs with any lesions, or target lesion size. Consistent with primary/secondary efficacy endpoints in ITT pts, PFS and ORR were evaluated per RECIST v1.1 by blinded independent central review in subgroups. Results: Median follow-up in ITT pts was 23.5 months. PFS, OS, and ORR (including complete response [CR]) outcomes are summarized in the table across subgroups: IMDC risk (favorable [FAV], intermediate [I], poor [P]); number of organs with ≥ 1 target/nontarget lesion (T/NT; 1 and ≥ 2); sum of diameters of target lesions (sDTL; < and ≥ median [72.1 mm]), and in pts with liver, bone, or lung mets. The PFS HR favored N+C vs S and median (m) PFS was longer with N+C vs S across all subgroups. The OS HR also favored N+C vs S across most subgroups. ORR ranged from 38%–66% (N+C) vs 10%–44% (S) across subgroups, and CR benefits were seen with N+C in most subgroups. Additional outcomes including landmark OS and response details in subgroups will be reported. Conclusions: Consistent with outcomes in ITT pts, efficacy benefits with N+C vs S were observed regardless of IMDC risk status, organ site of mets, or extent of tumor burden at baseline. These results support N+C as a new first-line treatment option for pts with aRCC. Clinical trial information: NCT03141177. [Table: see text]

Abstract PD13-06: Incidence and management of central nervous system metastases in patients with inflammatory breast cancer

Abstract Background: Patients (pts) with inflammatory breast cancer (IBC) have a high risk of central nervous system (CNS) metastasis (mets) with their associated impact on longevity and quality of life. Given evolving CNS-directed treatments, including focal radiation (RT), we compared the proportion of pts diagnosed with asymptomatic CNS mets before and after 2012 as data from Phase III trials in the preceding years (yr) increasingly supported the use of stereotactic radiosurgery (SRS). Specific attention was paid to pts treated with tri-modality therapy (TMT), defined as preoperative systemic therapy, surgery, and RT to determine whether screening for asymptomatic CNS mets would be beneficial. Methods: We retrospectively reviewed the records of pts diagnosed with IBC 1997-2019 and enrolled in an IRB-approved registry at a dedicated IBC center. CNS met-free survival time was defined as the time from IBC diagnosis to date of CNS mets. Alive CNS met-free pts were censored at their latest survival date and death was treated as a competing risk. Cumulative CNS mets incidence was computed. Analyses were stratified based on stage at diagnosis (III vs. de novo IV) and receipt of TMT. For pts completing TMT, the completion date was the starting point for cumulative incidence calculations. Overall survival (OS) was estimated as the time from CNS mets diagnosis to death, with censoring for pts who were still alive. Results: A total of 531 pts were identified; 372 (70%) with stage III; 159 (30%) with de novo Stage IV disease. The median follow-up for pts presenting with stage III and stage IV disease at diagnosis was 5.6 yr and 1.8 yr, respectively. 124 pts had CNS mets; 5 of them at diagnosis. CNS was the first site of mets or progression in 50 pts (9.4%). The cumulative incidence of CNS mets stratified by stage at diagnosis and receipt of TMT is seen in Table 1. Among the 50 de novo Stage IV pts who completed TMT, 4 developed CNS mets prior to surgery. The median overall survival (mOS) after CNS mets was 0.6 yr (IQR: 0.2 - 1.4). Results stratified by tumor subtype were: HER2+ disease (n=51) 1.4 yr (IQR: 0.6 - 3.7); hormone receptor+/HER2- (n=27) 0.6 yr (IQR: 0.2 - 1.2); triple negative (n=40) 0.2 yr (IQR: 0.1 - 0.5). Most pts with CNS mets (87/124, 70%) had neurologic symptoms prompting imaging. There was no difference in the proportion of asymptomatic pts diagnosed with CNS mets prior to or after 2012. Management of CNS mets was as follows: 47 pts (38%) received whole brain RT (WBRT) alone, 22 (18%) SRS alone, 15 WBRT + SRS (12%), 6 resection + WBRT (5%), and 5 resection + SRS (4%). The remaining pts received several of these modalities with or without intrathecal chemotherapy (13, 11%) or CNS treatment was not documented (16, 13%). A total of 258/531 pts have died (49%). Of these pts, 103 (40%) had CNS mets. 67/103 (65%) died due to CNS mets. Conclusions: Among pts with IBC completing TMT, the incidence of CNS mets is as high as 20% both in de novo Stage IV pts at 1 yr and in Stage III pts within 5 yrs, supporting routine surveillance brain MRI among pt with Stage IV disease. The majority of pts continue to receive WBRT with its resultant toxicities. Efforts should be made to identify CNS mets early to facilitate more focal therapy. Future research on systemic therapy with CNS penetrance for IBC patients should be pursued. These data support an ongoing prospective study of screening brain MRI in pts with Stage III IBC to quantify the incidence of CNS mets, utilization of WBRT and impact on neurologic quality of life (NCT04030507). Cumulative Incidence of CNS MetsNo.1 year (95% CI)2 year (95% CI)3 year (95% CI)Stage III (All)3725% (3-7)9% (6-12)18% (14-23)Stage IV (All)15417% (12-24)30% (22-37)42% (32-51)Stage III (TMT)3045% (3-8)11% (8-16)19% (14-24)Stage IV (TMT)4621% (10-34)28% (16-43)35% (20-50) Citation Format: Laura Warren, Samuel M Niman, Marie Claire Remolano, Jean Landry, Faina Nakhlis, Jennifer R Bellon, Meredith M Regan, Beth A Overmoyer. Incidence and management of central nervous system metastases in patients with inflammatory breast cancer [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 PD13-06.

MON-491 TRK-Fusion Thyroid Cancer: A Clinical Overview in a Large Population at a Single Cancer Center

Introduction: Most thyroid cancers (TC) are due to mutually exclusive somatic driver mutations. NTRK fusions are rare oncogenic drivers in papillary TC (PTC), poorly differentiated TC (PDTC) and anaplastic TC (ATC), estimated to be in 2.3% of all TC. However, the clinical presentation and behavior of TRK-fusion TC remains largely unknown. Methods / Case Presentation: Using institutional databases, we identified all TC patients (pts) with an NTRK fusion reported on somatic testing performed by a CLIA-certified laboratory. Data from the medical records were collected. The objective of this study was to investigate the clinical and pathological features of TC pts whose tumors harbored an NTRK fusion. Results / Discussion: We identified 36 TC pts with somatic NTRK fusions. Fusion testing was generally done in pts with advanced or radioactive iodine refractory (RAI-R) disease. Median age at diagnosis was 27.4 years (range 4–75 years), 21 (58%) were female and 16 (44%) were pediatric. 28/36 (78%) pts had PTC, 2/36 (5%) PDTC and 6/36 (17%) ATC. There were a total of 12 (33%) NTRK1, 24 (67%) NTRK3, and no NTRK2 fusions. In ATC and PDTC pts NTRK3 was the most common NTRK fusion 7/8 (87%). In PTC pts, 11 (39%) had NTRK1 and 17 (61%) had NTRK3. In the adult pts NTRK3 was more common 17/20 (85%) (Odds Ratio 7.2, P=0.013), however, in pediatric pts rate of NTRK1 and NTRK3 were similar. One pt had additional mutations along with the NTRK fusion, an ATC pt with multiple mutations including BRAF V600E. Of the 30 PTC/PDTC pts, 23 (77%) had distant metastases (mets). 14 (38%) pts had distant mets at diagnosis and 11 (69%) pediatric pts had distant mets. Lung 21 (70%) and bone 9 (30%) were the most common distant mets sites. In the PTC pts with distant mets, 9 (41%) had RAI-avid and 11 (50%) had RAI-R disease. In the entire cohort of 36 pts, 17 (53%) were on a systemic therapy of whom 11 pts were PTC. NTRK directed was the most common systemic therapy 16 (94%). All PTC pts were alive with a median time from diagnosis of 46 months (Interquartile 1–3: 25–118 months). Four ATC and one PDTC pts had died at the time of the analysis. Conclusions: In this study we confirmed that NTRK fusions occur primarily in PTC but also in less differentiated tumors. Most were young pts but NTRK fusions were identified in tumors from adults as old as 75 years. NTRK1 and NTRK3 were the most common NTRK fusions with NTRK3 being more common in adults. In thyrocyte-derived TC pts, NTRK fusions are mutually exclusive genetic events that occur in pts of all ages and varying histologies. Given the availability of NTRK targeted therapy, consideration should be given to testing for NTRK fusions in advanced thyroid cancer pts, especially those in whom prior genetic testing did not identify an oncogenic driver.

Survival outcomes in stage IV small-cell lung cancer (IV-SCLC): Analysis from SEER database

Abstract Background SCLC represents the subtype with worst survival among lung cancer patients. Despite initial good response to platinum based chemotherapy in extensive disease, these patients relapse fast with an unfortunate prognosis. The majority of overall survival (OS) data reported show a median between 8-10 months (mo) based on randomized clinical trials and meta-analysis. Methods The aim of this study is to analyze survival outcomes in IV-SCLC patients in real clinical practice based on SEER database and identify which patients have worse outcomes. We selected all patients with SCLC from SEER database diagnosed between 2010-2015. Bivariate analysis was used by chi-square determination for the association of binary qualitative variables and the ANOVA test to compare 2 or more variables. A multivariate analysis using Cox regression was performed, measuring the effect by Hazard Ratios (HR) and their 95% confidence intervals to determine the impact of these prognostic factors on OS. AJCC 7 was used for TNM staging. Results We included 26,221 patients with SCLC. Men: 50.7%. 55.7% patients were ≥ 65 years old. Median age: 67 years old. 82% were caucasian. 70.84% were stage IV. These patients showed a median OS (mOS) of 6mo (5.83-6.17). 45.37% of them had liver metastasis (mets), bone: 33.41%, brain: 23.86%, lung: 19.47% and other mets sites: 16.88%. Median OS in patients with liver mets, bone, brain and lung were 4 (3.79-4.21), 6 (5.74-6.26), 6 (5.71-6.29) and 5 mo (4.63-5.37) respectively. Patients involving both lung and liver mets with 3 or more mets sites showed the worst survival with 3 (1.99-4.00) and 4 (3.11-4.89) mo of mOS respectively. The percentage of patients alive at 6, 12, 24 y 60 mo were 47.70%, 21.64%, 5.91% and 1.61% respectively. Conclusion This real world data analysis reflects that the chance of having long term survivors in SCLC is very low and that mOS has not been improved over the last years. The introduction of new therapies such as immune checkpoints opens a new opportunity for long term survival and better outcomes in this aggressive disease. Legal entity responsible for the study Roche Farma S.A. Funding Roche Farma S.A. Disclosure J. de Castro Carpeno: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZ; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: Tesaro. M. Cobo Dols: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZ; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Boehringer. M. Domine Gomez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZ; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Abbvie; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer. P. Ruiz Gracia: Full / Part-time employment: Roche. L. Crama: Full / Part-time employment: Roche. M.R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Abbvie; Advisory / Consultancy, Speaker Bureau / Expert testimony: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer.

Novel risk stratification criteria of metastatic renal cell carcinoma (mRCC) patients (pts) treated with immune checkpoint inhibitors (ICI).

e16068 Background: IMDC risk criteria is the gold standard for predicting outcomes for mRCC pts. We developed novel risk groups for mRCC pts treated with ICI. Methods: We performed a retrospective review of 100 ICI-treated mRCC pts at Winship Cancer Institute from 2015-2018. Overall survival (OS) and progression-free survival (PFS) were used to measure outcomes; OS was the primary outcome. We obtained baseline monocyte-to-lymphocyte ratio (MLR), body mass index (BMI), and metastatic (met) sites. We created a new variable (D_met) that combines number and sites of met: 0 = < 2 met sites; 1 = ≥ 2 met sites without liver metastases (mets); 2 = ≥ 2 met sites with liver mets. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS. Recursive partitioning and regression tree analyses were used for risk stratification. Discrimination of the risk score was measured by Uno C-statistics. Results: The pts were 66% males, 78% clear cell RCC (ccRCC), and 71% received anti-PD-1 monotherapy. Very poor risk pts (MLR ≥ 0.93 or MLR < 0.93, BMI < 24, and D_Met = 2) had significantly shorter OS and PFS than good risk pts (MLR < 0.93, BMI ≥ 24, and D_Met = 0) in univariable and multivariable analysis (UVA and MVA, Table). The Uno C-statistic for our risk grouping criteria compared to IMDC is 0.687 vs 0.566 (p = 0.061) for OS and 0.594 vs 0.541 (p = 0.78) for PFS. Conclusions: Risk grouping using MLR, BMI, and number and sites of mets may predict survival in mRCC pts treated with ICI. These results should be validated in a larger, prospective study. [Table: see text]

Multidisciplinary treatment of 99 adult osteosarcoma (OST) patients (pts) with synchronous and metachronous metastases (mets): A retrospective series of the French Sarcoma Group (FSG).

11030 Background: Treatment (trt) options for metastatic OST are scarce. Following failure of standard 1st line therapy pts who relapse present a challenging trt dilemma, and have poor prognosis. Surgical removal of all mets is essential. Currently, there are no standardized 2nd line trt options in relapsed OST. Methods: Pts were identified from 2 sarcoma databases; Netsarc and ConticaBase. Clinical data prospectively registered in the databases were supplemented with retrospective review of the medical records. Results: From January 2009 to December 2016, we identified 99 pts, in 12 FSG centers; 30 with synchronous (SC) and 69 with metachronous (MC) mets, with 62 males. Median age was 25 years (18-53). Total number of mets was 1 for 31 pts, 2-5 for 26 and > 5 for 42. Mets sites were lung, bone and other in 77, 14 and 22 pts respectively. Median time to first MC mets was 22 months (mo) (4-97). All pts except 10 with MC mets received a 1st line systemic trt for relapse, 65 a 2d-line, 38 a 3d-line, and 20 a 4th line, with 27 pts included in a clinical trial. Sixty five pts had local trt of distant mets (surgery for 54, irradiation for 5 and radioablation for 6). Eighteen pts had repeated thoracotomies (2 for 13 pts, 3 for 5, 1 for 1 pt). Nine of 10 MC mets pts (with ≤ 5mets) who never received any systemic trt had complete mets resection, 1 had mets radioablation, all were alive at last follow-up (FU). Median FU was 16.5 mo (2-132). Median progression free survival (PFS) and overall survival (OS) were 5.5 (95%CI 4-7) and 16.5 mo (95%CI 10-25) respectively. In multivariate analysis; > 5 mets, time to 1st mets < 24 mo, were negative prognostic factors on OS and PFS (p= 0.03, 0.01 and p=0.013, 0.00 respectively). Bone mets and absence of mets surgery were negative prognostic factors on OS only (with p=0.012, 0.008). Conclusions: Adult OST pts with distant mets are heterogeneous with poor prognosis. Complete surgery of distant mets remains essential. In reference sarcoma center, OST pts at relapse with > 1 mets commonly receive >1st line of systemic trt, and are included in clinical trial. Multidisciplinary trt combining complete mets local trt and systemic therapy seems to be rational.

Sites of metastasis (mets) and association with clinical outcomes (CO) in metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (cabo).

585 Background: Cabo is approved for the treatment for mRCC. We investigated the association of sites of mets and clinical outcomes (CO) in mRCC pts treated with cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016 to 2018. Overall survival (OS) and progression-free survival (PFS) were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. Objective response was defined as a complete response (CR) or partial response (PR). Sites of mets were obtained from radiology and clinic notes and included bone, lymph node, brain, lung, and liver. Univariate analysis (UVA) and multivariate analysis (MVA) was performed using Cox proportional hazard or logistic regression model. Results: The median age was 63 years and most (68%) were males. The majority of pts (79%) had ccRCC and 48% received at least 2 prior systemic treatments. The distribution of mets were: bone (42%), lymph node (69%), brain (6%), lung (83%), and liver (40%). The UVA and MVA of association between sites of mets and CO are presented in Table. Pts with bone mets had significantly longer OS in UVA and trended towards longer OS and PFS in MVA compared to pts without bone mets. Conclusions: Bone mets may be a prognostic factor for improved CO in mRCC pts treated with cabo. Larger studies are needed to validate the results of this study. UVA and MVA† of bone metastases and CO. [Table: see text]

Sites of metastases (mets) and their association with clinical outcomes (CO) in urothelial cancer patients (pts) treated with immunotherapy (IO).

473 Background: Several IO agents have been approved for treatment of advanced urothelial cancer pts. We investigated the association between sites of mets and CO in urothelial cancer pts treated with IO in the real world setting. Methods: We performed a retrospective review of 67 urothelial cancer pts treated with PD-1 or PD-L1 inhibitors at Winship Cancer Institute from 2015-2018. Overall survival (OS) and progression free survival (PFS) were measured from first dose of IO to date of death or hospice referral and radiographic or clinical progression, respectively. Sites of mets were collected from radiology and clinic notes at baseline. Univariate analysis (UVA) and multivariable analysis (MVA) used Cox proportional hazard. Results: The median age was 70 and most (79.1%) were men. Pts had mets to sites such as lymph node (73.1%), bone (29.9%), liver (20.9%), lung (31.3%), and brain (1.5%). Pts with bone or liver mets had significantly shorter OS and PFS in UVA. Pts with bone mets also had significantly shorter OS and PFS in MVA (Table). The median OS of pts with bone mets was 2.2 months (12-month survival=28.0%), while those without bone mets had a median OS of 21.9 months (12-month survival=52.5%) per Kaplan-Meier estimation. The median OS of pts with liver mets was 2.2 months (12-month survival=28.6%), while those without liver mets had a median OS of 12.8 months (12-month survival=50.1%) per Kaplan-Meier estimation. Conclusions: Bone and liver mets are poor prognostic factors in urothelial cancer pts receiving IO in the real world setting. These findings should be validated in a larger study. [Table: see text]

Eficacy and safety of first-line TKI in elderly with metastatic renal cancer.

588 Background: Data on 1st line treatment with tyrosine kinase inhibitors (TKI) in elderly patients(pts) with metastatic renal cell carcinoma (mRCC) is controversial, and there is rationale for inferior outcomes due to multiple comorbidities and polypharmacy. We aimed to compare the efficacy and safety between the elderly (E) and non-elderly (NE) in 1st line therapy, and to explore factors influencing survival and toxicity. Methods: We retrospectively reviewed all medical records of mRCC pts treated with 1st line TKI at our institution (2007 – 2018). Categorial variables were compared by Fisher’s exact test and continuous, Mann–Whitney. Survival was estimated by Kaplan-Maier method, prognostic factors adjusted by Cox regression model. Results: From 171 eligible pts, 64 (37.4%) had ≥ 65years old, with median age of 70.5 for E and 56 for NE. In both groups most were male, had clear cell histology, good/intermediate IMDC risk, prior nephrectomy and > 1 metastatic (mets) site. Sites of mets were evenly distributed. E pts had more diabetes (35.9 vs16.8%, p.009) , hypertension (67.2 vs 46.7%, p.01), cardiovascular disease (15.6 vs 6.5%, p.06), moderate/severe renal dysfunction (62.5 vs 28.8%, p < 0001), high Charlson Comorbidities Index (CCI≥3, 48.4% vs 20.8%, p < .0001), polypharmacy (34.4 vs15.9%, p.008), worst ECOG (≥2, 28.2 vs 12.3%, p.01), and a trend to worst nutrition (weight loss 35.9 vs 22.5%, p.07). Sunitinib was used for 60.9 vs 79.4%, Pazopanib 35.9 vs 18.7%, Sorafenib 3.1 vs 1.9%, comparing E and NE pts. Median overall survival (OS) and progression free survival (PFS) was 23.7 vs 25.6m (p.8) and 9.3 vs 10.9m (p.7), respectively. After adjusting for prognostic factors, age continues not to influence OS (HR 1.17, IC95 0.77-1.78, p.45). Grade (G) 3/4 toxicity was seen in 59.4 vs 53.3%, dose reduction in 54.7 vs 53.3% and suspension due to toxicity 25 vs 13.3% for E and NE, respectively. In the E, none of the comorbidities, CCI or polypharmacy impaired OS or toxicity, but pts using sunitinibe had greater G3/4 toxicity than with pazopanib (71.8 vs 39.1%, p.02). Conclusions: Elderly had similar outcomes to NE pts, despite greater comorbidities and polypharmacy, hence efficacious therapies shouldn’t avoided. Pazopanib seems to be safer in this subgroup.

The outcome of patients (pts) with metastatic colorectal cancer (mCRC) based on site of metastases (mets) and the impact of molecular markers and site of primary cancer on metastatic pattern.

3560 Background: Although liver is the commonest site of mets in pts with CRC, pattern of spread is variable and may reflect different biology in different subsets of pts. Methods: This is a retrospective analysis to explore the outcome of pts with mCRC based on their site of mets at diagnosis and to identify tumor characteristics which could predict the site of mets. Pts from 2 Australian databases, BioGrid (BG) and South Australian Cancer Registry (SA), from 01/2006 to 12/2015 were grouped into 5 cohorts; lung only, liver only or any pts with brain, bone or peritoneal mets. Overall survival (OS) for each group was compared with the rest of the sample using Kaplan Meier analysis and the log rank test separately in each dataset. Mantel-Haenszel Chi-squared test was performed in pooled data to assess the association between KRAS, BRAF, Micro satellite instability (MSI), site of primary and site of mets. Results: 5967 pts were included. In both datasets median OS was significantly higher when mets were limited to lung or liver and shorter for those with brain, bone or peritoneal mets. BRAF, KRAS and MSI data were available for 20%, 37% and 21% of the sample. In the pooled analysis BRAF mutation was associated with brain (Relative Risk=5.2) and peritoneal mets (RR=1.8) with lower incidence of lung (RR=0.3) and liver (RR=0.7) limited mets. KRAS mutation was associated with lung only mets(RR=1.4). Left colon tumors were associated with bone (RR=1.6) and lung only mets (RR=2.3) while peritoneal spread was less frequent compared with right colon tumors(RR=0.6). Rectal cancer was strongly associated with brain, bone and lung mets (RR=1.7, 1.7, 2.0). MSI status was not associated with site of mets though liver only mets was less frequent in MSI high tumors. Conclusions: Survival duration with mCRC is related to the site of mets. OS was significantly better when mets were confined to either lung or liver. BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites like brain and bone. [Table: see text]

Androgen receptor (AR) activation in breast cancer (BC) liver metastases.

11619 Background: AR is expressed in the majority of BCs and its signaling may contribute to the development of BC metastases (mets). The expression pattern of AR, its phosphorylated form, p-AR S650, and correlations with other BC growth and survival pathways were evaluated in BC mets by reverse phase protein array (RPPA). Methods: RPPA was performed on 93 FFPE primary BCs and mets at a CLIA-certified laboratory. Immunostaining with 24 antibodies was directed against AR, p-AR S650, p-MET, and total and p-HER1/2/3 pathway proteins. Clinical and genomic data were obtained from pt chart review. Analysis of variance (ANOVA) was used to assess any statistically significant differences between the groups. Results: 35 tissues were primary BCs (38%); 58 were mets (62%). Sites of mets: liver (n = 41); lung (n = 8); chest wall (n = 9). Of the 41 liver mets, 2 were triple negative (TN), 32 were ER+/HER2-, and 7 were HER2+. AR expression was increased in chest wall (1.7-fold; p = 0.038) compared to primary BCs. p-AR was increased in liver (2.0-fold; p = 0.039) and chest wall (1.8-fold; p = 0.026) compared to primary BCs. ER+ liver mets especially showed strong liver-specific activation of AR along with overexpression of HER1, HER3, VEGFR, and activation of mTOR, S6 Ribo, 4EBP1, and STAT3. MEK/ERK pathway was not activated in ER+ liver mets. HER2+ liver mets had pan-HER1/2/3 activation along with MET, SRC, S6 Ribo, 4EBP1, and JAK2/STAT3. In the 2 TN liver mets, EGFR, VEGFR, mTOR, S6 Ribo, 4EBP1, and JAK2/STAT3 were activated while AR and MEK/ERK were not. The ER+ liver mets showed higher expression of p-AR (p = 0.079), p-HER3 (p = 0.002), p-HER2 (p = 0.010) and p-Jak2 (p = 0.002) compared to primary ER+ BCs whereas the HER2+ liver mets showed lower level of p-IGFR (p = 0.049) and p-MET (p = 0.010) compared to primary HER2+ BCs. Interestingly, TN chest wall mets had higher levels of AR and p-AR (p = 0.008 and 0.044 respectively) compared to TN BCs. Conclusions: ER+ liver mets have strong expression of AR and p-AR, and all liver met subtypes showed accumulation of S6 Ribo/4EBP1 and activation of JAK2/STAT3, but not the MAPK pathway. HER1/3 and HER1/2/3 were activated in ER+ and HER2+ liver mets, respectively. These data suggest that targeting AR, HER1/3, and mTOR in ER+ liver met would be of interest.