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5578 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that are potential therapeutic targets. We present an analysis of comprehensive genomic profiling (CGP) of a large series of low grade serous ovarian carcinoma patients assayed in a nationwide cancer network. Methods: 40 Pts with advanced low grade serous ovarian carcinoma (LGSOC) underwent hybrid-capture based CGP for up to 324 cancer-related genes on archival tumor tissue or 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 thru 06-2021. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 44 years (range, 25-65), 68% were White and 23% were Black. Genomic alterations (GA) were identified in 80% (32/40) of LGSOC, of which 22 (55%) had a clinically relevant genomic alteration (CRGA). There were no apparent racial differences between mutation frequencies. The table below details the frequency of the most common of these clinically relevant mutations. Additionally, 1 patient had an ESR1 activating mutation commonly seen in acquired hormone therapy resistance in breast cancer; and single cases of the following mutations were also noted: TSC1, PTCH1, PTEN, FGFR1, and AKT2. Conclusions: In a large series of Low Grade Serous Ovarian Cancer patients assayed with CGP, 55% of pts had mutations potentially targeted by precision medicine therapy. The most common target is KRAS, seen in 33% of patients, these are potentially treatable with FAK and MEK inhibitors. Another 10% of patients had either a BRCA or ATM mutations making PARP inhibitor therapy an additional targeted treatment option. While mutations in the RAS pathway are most common in LGSOC they are not the only actionable target. Furthermore, this approach might also help identify baseline or acquired resistance to the hormone therapies often used to treat this cancer. The results of this study demonstrate the significant heterogeneity of genomic alterations in this rare cancer and highlight the importance of genomic profiling in this cancer which has a marked propensity for recurrence. [Table: see text]

e17590 Background: Individualizing oncologic treatment by using precision oncology techniques that allow for detection of genomic alterations (GA) has become critical. We present an analysis of comprehensive genomic profiling (CGP) of a large series of high grade serous ovarian carcinoma (HGSOC) patients assayed in a nationwide cancer network. Racial disparities in genomic alterations may assist in better targeting therapies, predicting drug resistance, and potential germline mutations. Methods: 312 patients with HGSOC underwent CGP with hybrid capture on tumor tissue for treatment decision-making between 01-2013 to 06-2021. Clinically relevant genomic alterations (CRGA) were reported as targetable marker. Statistical analysis performed with Fisher Exact test. Results: Median age was 55 years (range, 23-81), 71.2% were White, 16.4% were Black, 3.9% were Hispanic, and 1.3% were Asian. GA were identified in 98.7% (308/312) of these patients. TP53 mutations were present in 286 of 312 patients (91.7%) and interestingly, while not statistically significant (p = 0.06) was present in 98% of black women and 89.2% of white women. BRCA1 mutation was present in 14.4% of white women and in 17.6% of black women. BRCA2 mutation was present in 9.9% of white women and 9.8% of black women. Several interesting mutations were identified, see table below. Conclusions: In this 312-patient series of women with HGSOC, we note several prominent mutations in the tumors. While not statistically significant, there is a trend of larger number of poorer prognostic mutations in black women including p53, KRAS and CCNE1. Some studies have found the amplification of CCNE1 and mutation of homologous recombination repair genes to be mutually exclusive in HGSOC which may compel us to find other therapeutic interventions than the PARP inhibitors for these patients.[Table: see text]

e17022 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of cervical cancer (CC) patients assayed in a nationwide cancer network. Methods: 118 Pts with advanced CC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 47 years (range, 27-71), 69% were Caucasian. GA were identified in 88% (104/118) of CC, of which 87 (74%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most commonpresent in 73.5% (64/87) of CC. CRGA in other targetable pathways were identified: 24.1% (21/87) in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2), 9.1% (8/87) in HRD (BRCA1/2, ATM, PALB2, BRIP1) and 24.1% (21/87) in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). One patient was MSI-high and one patient was TMB-high. 29.8% (26/87) of CC patients were ordered a genomically-matched treatment, and 24 pts received treatment; 61.5% (16/26) were agents that were FDA approved in a different tumor type, and 34.6% (9/26) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The PFS for non study related patients was 7 weeks and OS was 19 weeks. Conclusions: In a large series of Cervical Cancer patients assayed with CGP, 27.5% (24/87) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

e17067 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of OC assayed in a nationwide cancer network. Methods: 449 Pts with advanced OC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant (CR) GA were defined as associated with targeted therapies or mechanism-driven clinical trials. Treatment histories for the 449 patients were obtained with IRB-approved retrospective review. Results: Median age was 56 years (range, 23-83), 71% were Caucasian. GA were identified in 94% (420/449) of OC, of which 283 (63%) had a clinically relevant genomic alteration (CRGA). 24.0% in HRD ( BRCA1/2, ATM, PALB2, BRIP1). CRGA in other potentially targetable pathways were identified: 48.0% MEK pathway ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) CRGA, 33.5% PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7), and 10.6% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). All OC tested were microsatellite stable and only one patient had a tumor mutational burden > 20 muts/Mb. 21% (59/283) of OC patients were ordered a genomically-matched treatment, 58% (37/64) were agents that were FDA approved in a different tumor type, and 17% (11/64) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. For the off label non-study population the median PFS was 19 weeks, and the median OS was 34 weeks. Conclusions: In a large series of OC assayed with CGP, 21% of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

e17123 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of endometrial cancer (EC) patients assayed in a nationwide cancer network. Methods: 278 Pts with advanced EC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 59 years (range, 37-85), 58% were Caucasian. GA were identified in 97% (271/278) of EC, of which 218 (80%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most common, present in 63.8% of EC. CRGA in other targetable pathways were identified: 28.4% in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) , 12.5% in HRD (BRCA1/2, ATM, PALB2, BRIP1 ) and 9.9% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). 26 patients are MSI-high 9.5% (26/271) and 21 patients are TMB-high 7.7% (21/271). 29.8% (65/218) of EC patients were ordered a genomically-matched treatment, and 61 of these patients received the treatment. 69.2% (45/65) were agents that were FDA approved in a different tumor type, and 24.6% (16/65) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The median PFS for non-clinical trial study patients was 9 weeks, and the median OS was 27 weeks. Conclusions: In a large series of Endometrial and Uterine cancer patients assayed with CGP, 27.9% (61/218) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.