Pregnancy and lactation are special life stages that require regular nutritional and medical attention to help protect the health of the mother and promote the growth and development of the offspring. Despite an increased focus on maternal and fetal health over the last several decades, the rates of pregnancy-related morbidity and mortality are increasing in the United States (US). On average, Black women who are pregnant or lactating face greater health disparities and birth complications than other racial/ethnic groups in the US. The issues contributing to these disparities are multi-faceted and include sociocultural, economic, medical, and dietary factors. For example, Black women face greater rates of food insecurity, worse access to healthcare, and lower nutrient status when compared to White women. A growing body of research suggests that consuming a healthier dietary pattern is one of the most potent modifiable risk factors associated with improved fertility and reducing pregnancy-related complications. Recent publications have also shed light on the role of dairy foods in improving diet quality and nutrient status among Black women and for impacting maternal and fetal health outcomes, such as preeclampsia, spontaneous abortion, preterm birth, and fetal growth. To support healthy pregnancy and lactation, the current national dietary guidelines recommend the consumption of 3 servings of dairy foods per day. However, the vast majority of Black women in the US are falling short of these recommendations and are not meeting nutrient requirements for calcium and vitamin D. Therefore, strategies that target misconceptions surrounding lactose intolerance and focus on the health value of adequate dairy intake among Black women of child-bearing age may benefit both prenatal and postpartum health. This review presents the current evidence on health disparities faced by pregnant and lactating Black women in the US, and the role of dairy foods in supporting healthy pregnancy, fetal development, and lactation outcomes in this population.

TPS235 Background: A significant proportion of patients with GI adenocarcinomas remain at high risk of recurrence despite adjuvant therapies. Guanylyl cyclase C (GUCY2C) is expressed by normal intestinal cells and immunologically compartmentalized. Its overexpression in GI adenocarcinomas makes it an appealing target for anti-cancer therapies. We previously completed a phase I study of the Ad5-GUCY2C-PADRE vaccine in patients (pts) where it was safe and well tolerated (NCT01972737). Pre-existing neutralizing antibodies (NAbs) to the Ad5 vector opposed vaccine-induced immune responses. To overcome this challenge, we generated a GUCY2C vaccine employing a chimeric viral vector composed of the Ad5 capsid and Ad35 fiber protein (Ad5.F35). The extracellular domain of GUCY2C, along with the PADRE CD4+ helper T-cell epitope, were cloned into the Ad5.F35 viral vector to generate a replication-incompetent vaccine. Preclinical studies showed that Ad5.F35-GUCY2C-PADRE was less sensitive to pre-existing Ad5-specific immunity. Methods: This is a Phase 2A, dose-finding, single-center, open-label, randomized trial (NCT04111172) to evaluate the safety and immunogenic activity of three dose levels of Ad5.F35-GUCY2C-PADRE vaccine in adult pts with select solid tumors (colorectal, pancreatic, gastric, esophageal, or small bowel) who are at risk of relapse post definitive surgery and adjuvant therapy. Pts must enroll at 4-24 weeks from completion of standard therapies. Other key eligibility requirements include ECOG status of 0-1 and adequate organ function. Pts are randomized to one of three dose levels (1011 vp or viral particles, 1012 vp, or 5x1012 vp) with stratification by disease type. After completing an initial safety run-in for 9 pts (3 pts in each arm), the study will recruit up to 81 pts in total (27 in each arm). Pts will receive three successive doses of vaccine (4 weeks apart) and will undergo end-of-treatment assessment 4 weeks after their last vaccine. Pts are followed for disease status by scheduled follow-up until 2 years or recurrence, whichever occurs first. An interim futility analysis will be performed after 15 patients have completed treatment in each arm based on the Simon minimax design. Study objectives include assessment of safety and tolerability (primary), as well as T-cell and antibody responses to GUCY2C (secondary). Additional exploratory objectives include evaluating the relationship between NAbs and immune responses to GUCY2C, GUCY2C protein expression in tumors, circulating tumor DNA kinetics in relation to vaccination, and disease-free and overall survival (where applicable). Prespecified safety run-in has been completed without dose limiting toxicities; second stage accrual began in November 2021, and 43 out of 81 pts have been enrolled. Study enrollment is ongoing. Clinical trial information: NCT04111172 .

Background: The NCI-MATCH trial was designed to assess the clinical efficacy of select targeted therapies in pts with specific mutations in a tumor agnostic fashion. Loss of function mutations in the tumor suppressor genes TSC1 and TSC2 have been shown to activate the mTORC1 pathway constitutively. TAK-228 is an orally available potent inhibitor of both TORC1 and TORC2 complexes. Subprotocol M is a phase 2 study to determine the effects of TAK-228 on pts whose tumors harbor TSC1 or TSC2 alterations. Materials and Methods: Patients with advanced metastatic solid tumors or lymphomas who progressed following at least 1 prior systemic therapy were accrued to NCI-MATCH for tumor molecular profiling, and those with functionally curated somatic TSC1 or TSC2 alterations were offered participation in sub-protocol M. Patients received TAK-228 3 mg daily for 28-day cycles until progression or intolerable toxicity. Results: 49 pts were enrolled on arm M with 4 pts deemed ineligible or never starting treatment, leaving 45 evaluable pts. The primary analysis includes 34 pts with centrally confirmed mutations (CM), 7 from the MATCH screening cohort assay and 27 from approved outside laboratories. Of the 34 CM pts, 17 were female (50%), median age 62 (22–87), 21 had received 3 or more lines of prior therapy (61.7%), all had ECOG PS 0-1. Tumor types included urothelial (4), renal (2), prostate (2), colorectal (6), pancreas (1), HCC (1), ovary (3), endometrial stromal sarcoma (2), cervical adenocarcinoma (1), TNBC (1), squamous lung (2), PEComa (2), spindle cell sarcoma (1), PNET (1), angiosarcoma of spleen (1), osteosarcoma (1), melanoma (1), and undifferentiated carcinoma (2). TSC2 alterations made up 17 of the CM pts and 25 of the evaluable pts. Of the 34 CM pts, there were 5 PR for a 14.7% ORR (90% CI 6.0%- 28.5%), 13 SD, 12 PD and 4 were unevaluable. The estimated 6-month PFS rate is 28.7% (90% CI 17.3%–47.5%) in CM pts. The five responders were endometrial stromal sarcoma (1), high grade angiosarcoma of the spleen (1), PNET (1), HCC (1), and renal clear cell carcinoma (1). 4/5 responders had TSC2 alterations. Two pts with squamous NSCLC had clinical benefit for greater than 6 mo. Most common emergent adverse events among the 45 evaluable pts included hyperglycemia, fatigue, nausea, anemia and diarrhea. Grade 3–4 treatment-related adverse events (TRAE) included creatinine increase (4), TTP (4), dysphagia (4), pruritis (4). No grade 5 TRAE were reported. Six pts came off study due to adverse events. Conclusions: While the primary endpoint of 6/34 (17.6% ORR) CM responses was not met, TAK-228 therapy had modest clinical activity in pts with various solid tumors exhibiting TSC1 or TSC2 alterations. The observation that 4/17 (23.5%) tumors harboring confirmed TSC2 alterations responded in this heavily pretreated population merits further investigation. NCT02465060. No conflict of interest.

To assess the impact of clinical trial (CT) participation among patients with metastatic breast cancer (mBC pts). Adult females with mBC were selected from Flatiron Health EHR–derived de-identified database (diagnosis date between 2011-2021). Clinical trial participation was determined by having a "clinical study drug" in line of therapy (LOT), herein identified as the indexed LOT. CT enrollees were 1:2 matched to CT non-enrollees using receptor subtype, race and number of months between indexed LOT and metastatic diagnosis date to adjust for immortal time bias. Patients were then followed from the indexed LOT until the earliest occurrence of death, last activity date, or study end. Multivariate Cox regression was used to assess the impact of CT participation on patients' overall survival (OS). Covariates included in the Cox regression were age at metastatic diagnosis, practice type, region, insurance type, year of diagnosis, stage at diagnosis, number of metastasis sites and ECOG at 1L metastasis. Of 25,562 mBC pts in Flatiron Health mBC database, 747 CT enrollees met the inclusion criteria and were matched to 1,494 CT non-enrollees. CT enrollees were younger (58 yo vs 62 yo), more residing in the South (53% vs 39%), more had commercial health plans (51% vs 38%) and were more treated in academic settings (16% vs 8.3%). After controlling for baseline and clinical characteristics, the OS between CT enrollees and non-enrollees were similar (HR=0.93, 95% CI = 0.79, 1.09). Clinical trials enrollees had similar outcomes to those who did not participate in clinical trials. Future research should control for CT assignment (e.g., active treatment vs placebo).

The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.

FGFR2 fusions occur in 10–20% of pts with iCCA and comutations in tumor suppressor genes may be prognostic. FOENIX-CCA2 is a study of futibatinib (a highly selective irreversible FGFR1–4 inhibitor) in pts with iCCA and FGFR2 fusions/other rearrangements. Pts enrolled had locally advanced/metastatic iCCA with FGFR2 fusions/other rearrangements, progressive disease (PD) after ≥1 systemic therapy (tx), no prior FGFR inhibitor tx, and ECOG PS 0/1. Pts received oral futibatinib 20 mg 1x/day until PD/intolerance. Objective response rate (ORR; independent review) was the primary endpoint and duration of response (DOR), PFS and safety were secondary endpoints. Subanalyses by pt characteristic, fusion, comutation and prognostic factor were performed. Interim data for 67 pts (58% female; median age 57 y) with ≥6 mo of follow-up are reported. Pts had FGFR2 fusions (82%) or rearrangements (18%). The most frequent fusion was FGFR2-BICC1 (n=15). ORR was 37.3%, median DOR 8.3 mo, and disease control rate 82%. In pts with confirmed FGFR2 alterations, ORR was 36.2% (21/58 fusions) and 44.4% (4/9 rearrangements). ORR was 33.3% in pts with FGFR2-BICC1. Best overall response in pts with comutations of interest is shown in the table below. All baseline characteristic subgroups (eg, age, gender, prior tx) had responding pts, including pts aged ≥65 y (ORR=57%; 8/14). Higher phosphate levels trended in responders vs nonresponders. Grade ≥3 treatment-related hyperphosphatemia resolved in a median of 6 d. Management of special interest AEs will be presented.Table: 54PComutationPatients, nCRPRSDPDFGFR2 fusionFGFR2 rearrangementBAP1 (n=3)003021IDH1 (n=3)021021TP53 (n=6)103233PBRM1 (n=3)001230PI3K genesa (n=4)013013CR, complete response; PD, disease progression; PR, partial response; SD, stable disease. aTwo mutations in PIK3A, 1 in PIK3B, and 1 in PIK3R1. Open table in a new tab CR, complete response; PD, disease progression; PR, partial response; SD, stable disease. aTwo mutations in PIK3A, 1 in PIK3B, and 1 in PIK3R1. These interim data demonstrate manageable AEs and efficacy of futibatinib in iCCA with FGFR2 fusions/other rearrangements. Responses were observed across pt subgroups, including those with common FGFR2 fusions, comutations, and poor prognostic factors.

iCCA has a poor prognosis and its incidence is higher in Asian vs Western countries. Futibatinib is an oral, highly selective, irreversible FGFR1–4 inhibitor that demonstrated safety and preliminary efficacy in pts with iCCA harboring FGFR2 aberrations. This study evaluated safety, efficacy, and QoL with futibatinib treatment in pts with iCCA and FGFR2 fusions/rearrangements. FOENIX-CCA2 (NCT02052778), a global phase II study, enrolled pts with unresectable/metastatic iCCA harboring an FGFR2 fusion/rearrangement and disease progression after ≥1 line of systemic therapy (including gemcitabine–cisplatin) but no prior FGFR inhibitors. Pts received futibatinib 20 mg once daily until disease progression/intolerability. The primary endpoint was objective response rate (ORR) per independent central radiology review and RECIST v1.1; secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), safety, and patient-reported outcomes (PROs). ORRs of subgroups by baseline demographic, fusion partner, and other molecular alteration (eg, TP53) were also determined. Of 103 enrolled pts, planned interim data are reported for 67 pts (54% white, 24% Asian) with ≥6 mo of follow-up; 55% of pts received ≥2 prior therapy lines, and 82% had tumors harboring an FGFR2 fusion (BICC1, n=15). ORR was 37.3%, DCR was 82.1%, and median DOR was 8.3 mo. Objective responses occurred regardless of baseline characteristic (subgroup: ≥65 y, ORR: 57.1%), FGFR2 fusion partner (BICC1, 33.3%), or other genetic mutation (TP53, 16.7%). Median PFS was 7.2 mo. The most common treatment-related adverse events (TRAEs; any grade/grade 3) were hyperphosphatemia (81%/27%), diarrhea (37%/0%), and dry mouth (33%/0%); no grade 4–5 TRAEs occurred. TRAEs were managed with dose interruption/reduction (55%/51%); only 1 pt discontinued due to a TRAE. PROs were stable through 273 days (13 cycles) of treatment. Futibatinib resulted in durable objective responses in pts with iCCA and FGFR2 fusions/rearrangements, including within pt subgroups. Adverse events were manageable, and QoL was maintained.

As cancer survivorship increases, mitigating and managing treatment related toxicities is an essential component of multidisciplinary oncologic care. It is known that sexual dysfunction in cancer survivors is a common and distressing consequence of treatment. We sought to determine the prevalence of sexual dysfunction, to characterize physician identification and management of this toxicity, and to find solutions for intervention. An IRB approved questionnaire, developed with input from radiation oncologists, medical oncologists and surgeons was administered from 2017-2019, on social media and in clinic using an iPad. The survey consisted of more than 25 questions and was targeted specifically to cancer survivors. Patients with missing data were excluded from the analysis. Descriptive analyses were done with frequency counts and percentages. Differences in response by gender were assessed using Chi-Square tests for categorical variables and ANOVA for Likert responses with a p < 0.05 being significant. 405 cancer survivors responded to the survey; 391 (96.5%) patients were included. Most were female (n = 313, 81.0%), between 41-50 years old (n = 115, 30.0) and had cancer types such as breast (66.8%), or pelvic tumors including prostate (16.3%), endometrial (6.1%), bladder (3.8%) and rectal (1.8%) cancer. Overall, 47.4% of patients received anti- hormone therapy, 78.1% received chemotherapy and 54.2% received radiation therapy. Forty-four percent of respondents were preemptively told that sexual health could be affected. Most (n = 337, 87%) of respondents stated cancer treatment impacted their sexual function or desire with 53.8% reporting body image distortion, 73.4% with dyspareunia, and 42.3% unable to achieve orgasm. Only 27.9% of respondents stated they had been formally asked about their sexual health from a provider. Male patients were significantly more likely to have been asked than female patients (53% vs. 22%, p<0.001). Standardized sexual health questionnaires were administered to 31.5% of male cancer survivors and only 5.4% of female cancer survivors (p = 0.001) but 51% of all patients state that they would be most comfortable with the conversation about sexual health to be initiated by their provider after being given a questionnaire to drive that conversation. We identified sexual dysfunction as a treatment side effect experienced by the majority of our cancer survivors that is not well addressed. Female survivors were significantly less likely to have their sexual dysfunction addressed. As discomfort surrounding sexual health is present, we demonstrate the utility of using validated sexual health questionnaires for both male and female cancer survivors to improve physician engagement, and facilitate open discussion between patients and providers to improve the quality of life of our patients.

NCI-MATCH assigned patients (pts) with advanced cancer and progression on prior treatment to targeted therapies, based on genomic alterations in pre-treatment tumour tissue. Arm J evaluated the combination of trastuzumab/pertuzumab (HP) across HER-2 amplified tumours. Eligible pts had HER2 amplification (copy number [CN] ≥7) detected by central next generation sequencing (NGS) or through NCI designated laboratories. Pts with breast/gastroesophageal adenocarcinoma, and those who received prior HER2-directed therapy, were excluded. Enrolment of pts with colorectal cancer was capped at 4 based on emerging data. Pts received HP IV Q3 weeks until disease progression or unacceptable toxicity, with restaging q3 cycles. Primary endpoint was objective response (ORR); enrolment of 35 pts provided 92% power to distinguish an ORR of 25% from a null of 5%, with one-sided type 1 error of 1.8%. Secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Data cut was 8-FEB-2020. 35 pts were enrolled 3/2017-6/2019; 2 were ineligible. Tumour types included gynecologic (n=14), hepatobiliary (10), colorectal (4), urothelial (3), esophageal squamous, and salivary gland (1 each). 58% were women, and 79% Caucasian. Median age was 64 (range 31-83), and 51% had ≥3 prior therapies (range 1- 11). Median cycles received was 3 (1-20). Of 33 treated, 24 had CN ≥7 confirmed by central lab (median CN=28). The confirmed ORR was 8.3% (2/24 partial responses [colorectal and cholangiocarcinoma], 90% CI 1.5-24%). There was one additional unconfirmed partial response (PR, urothelial cancer). Median PFS was 3.3 months (90% CI 2.0 - 4.6), 6-month PFS 23.3% (90% CI 13.6 – 40.1) and median OS 8.1 months (90% CI 5.5 - 12.4). Treatment-emergent adverse events were consistent with prior HP studies. There was no association between HER2 CN and response. HP had activity in a minority of tumours in this population, but did not meet the predefined efficacy benchmark for non-breast/gastroesophageal cancers with HER2 amplifications by NGS. Translational studies will focus on mechanisms of response and resistance.

Socioeconomic inequities have direct implications in COVID presentation, severity of illness and prognosis. From practice of prophylactic measures to availability of personal protective equipment, from access to diagnostic tests to treatment resources, there are many facets and distinct disease processes of a virus that, among many things, serves to expose and highlight our global disparities.

Patients with brain cancer are at risk for developing financial toxicity, which is defined as a combination of subjective financial concerns (eg, anxiety), objective financial consequences of health issues and treatments (eg, decreased income, medical debt), and patients' coping behaviors [ 1 Altice C.K. Banegas M.P. Tucker-Seeley R.D. Yabroff K.R. Financial hardships experienced by cancer survivors: a systematic review. J Natl Cancer Inst. 2016 Oct 20; 109 (pii: djw205. Print 2017 Feb) Crossref Scopus (276) Google Scholar ]. The direct costs of care are considerably high in these patients (monthly direct medical cost of approximately $8,478 [ 2 Chang S. Long S.R. Kutikova L. et al. Estimating the cost of cancer: results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000. J Clin Oncol. 2004; 22: 3524-3530 Crossref PubMed Scopus (158) Google Scholar ]), and decreased household income is common and reported by at least one-half of the patients as a result of cancer treatment [ 3 Johannesen T.B. Norum J. Lote K. Scheie D. Hirschberg H. A cost-minimising analysis of standard radiotherapy and two experimental therapies in glioblastoma. Radiother Oncol. 2002; 62: 227-231 Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar ]. Financial toxicity has been shown to be linked with several clinically relevant patient outcomes, including health-related quality of life [ 4 Zafar S.Y. McNeil R.B. Thomas C.M. Lathan C.S. Ayanian J.Z. Provenzale D. Population-based assessment of cancer survivors' financial burden and quality of life: a prospective cohort study. J Oncol Pract. 2015; 11: 145-150 Crossref PubMed Scopus (167) Google Scholar ], symptom burden [ 5 Lathan C.S. Cronin A. Tucker-Seeley R. Zafar S.Y. Ayanian J.Z. Schrag D. Association of financial strain with symptom burden and quality of life for patients with lung or colorectal cancer. J Clin Oncol. 2016; 34: 1732-1740 Crossref PubMed Scopus (162) Google Scholar ], care adherence [ 6 Neugut A.I. Subar M. Wilde E.T. et al. Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer. J Clin Oncol. 2011; 29: 2534-2542 Crossref PubMed Scopus (223) Google Scholar ], and survival [ 7 Ramsey S.D. Bansal A. Fedorenko C.R. et al. Financial Insolvency as a risk factor for early mortality among patients with cancer. J Clin Oncol. 2016; 34: 980-986 Crossref PubMed Scopus (350) Google Scholar ]. Extreme financial distress after cancer diagnosis (manifested by declaring personal bankruptcy) has been reported to be a risk factor for mortality [ 7 Ramsey S.D. Bansal A. Fedorenko C.R. et al. Financial Insolvency as a risk factor for early mortality among patients with cancer. J Clin Oncol. 2016; 34: 980-986 Crossref PubMed Scopus (350) Google Scholar ]. Given delay or nonreceipt of an indicated imaging test is a potential outcome of financial toxicity, it is critical for radiologists to understand the financial impact of treatment, which includes surveillance imaging, among patients with this condition.

Inflammatory breast cancer (IBC) is a rare aggressive form of cancer with poor outcomes. It accounts for about 1% to 5% of all breast cancer with the average diagnosis age of 52. The purpose of this study is to assess the relationship between age and initial surgical resection and mortality among patients diagnosed with IBC. We conducted a retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) program for women with IBC, aged 18 and older and diagnosed between 1991 and 2015. To understand the variations of age on receiving initial surgical resection and IBC-specific mortality, age was divided into four age categories (18-49 (younger), 50-64, 65-74, or 75+). Initial surgical resection was defined as complete resection. A multivariable logistic regression model was used to assess the association of age with initial surgical resection. A multivariable cox-proportional hazards model was used to assess the association between age and IBC-specific mortality. A total of 14,503 IBC women were identified and the age distribution was: 18-49 (27%), 50-54 (39%), 65-74 (17%), and 75+ (15%). A total of 4,555 (31%) women did not receive surgical resection. The older population had lower odds for receiving initial surgical resection (OR=0.85 (95%CI:0.76-0.94), OR=0.67 (95%CI:0.59-0.76), and OR=0.44 (95%CI 0.38-0.50) for age groups 50-64, 65-74, and 75+, respectively) compared to younger women. Older women had a higher risk of IBC-specific mortality (HR=1.11 (95%CI:1.03-1.19) and HR=1.39 (95%CI:1.29-1.51) for age groups 65-74 and 75+, respectively) than the younger groups. Increase age may be associated with lower odds of receiving initial surgical resection and a greater risk for IBC-specific mortality. Further research is needed to examine other patient, treatment and tumor specific characteristics that may affect these findings.

Breast cancer treatment guidelines recommend locoregional treatment consisting of breast-conserving surgery (BCS) plus radiation therapy (RT) or mastectomy (M) for Stage I-II female breast cancer. This study examines the relationship of breast subtype with locoregional treatment. The Surveillance, Epidemiology, and End Results Program registry database was used to evaluate females age 18-64 years diagnosed from 2010-2013 with Stage I-II breast cancer. The exposure of interest was breast subtype: HR+/Her2-, HR+/Her2+, HR-/Her2+, or HR-/Her2-. The outcome of interest was locoregional treatment: BCS+RT, BCS alone, M+RT, or mastectomy alone. The population was stratified by age (18-44 years and 45-64 years) and race/ethnicity (non-Hispanic (NH) white, NH black, NH Asian/Pacific Islander, and Hispanic). Multinomial logistic models were fit within each strata to determine the association between breast subtype and locoregional treatment, adjusting for demographic and clinical variables. 84,111 patients were included. 18-44 years old cohort: Compared to women with HR+/Her2- cancers, the odds (OR, 95% CI) of receiving BCS alone versus BCS+RT were increased among NH whites (1.57, 1.01-2.43) and NH blacks (2.53, 1.26-5.08) with HR-/Her2+ cancers. NH whites with HR+/Her2+ and HR-/Her2+ had increased odds of receiving M+RT versus BCS+RT (1.49, 1.22-1.82 and 1.94, 1.36-2.79, respectively). 45-64 years old cohort: Women with Her2+ tumors had increased odds of receiving mastectomy alone versus BCS+RT, regardless of race/ethnicity. NH whites, NH blacks, and Hispanics with HR-/Her2+ tumors had increased odds of receiving M+RT versus BCS+RT (2.17, 1.79-2.63; 1.53, 1.05-2.23; and 1.57, 1.03-2.39, respectively), but this relationship was not observed among NH Asian/Pacific Islanders. Variability in surgical and radiation therapy treatment patterns was observed by breast subtype across race/ethnicity strata and between age groups. Additional research is needed to understand how breast subtype is and should be considered by patients and providers in locoregional treatment decisions.

Background: The NCI-MATCH trial is the largest national study (1173 sites) for pts with relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns targeted therapies based on individual tumor molecular alterations detected using the adapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC). We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and P may benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD > 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD > 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss. Clinical trial identification: NCT02465060. Legal entity responsible for the study: NCI ECOG-ACRIN. Funding: NCI ECOG-ACRIN. Disclosure: F. Janku: Research support: Bristol-Myers Squibb, Novartis, Genentech, FujiFilm Pharmaceuticals, Plexxikon, Deciphera, Symphogen, Piqur, BioMed Valley Discoveries, and Upsher Smith Laboratories; Scientific Advisory Boards: Deciphera, Guardant Health, IFM Therapeutics; Consultant: Immunomet and Trovagene; Ownership interests: Trovagene. S.L. Puhalla: Consultant: AbbVie, MedImmune, Celldex, Puma, Pfizer, AstraZeneca, Esai, nanostring; Research funding to institution: AbbVie, Pfizer, Lilly, Novartis, Incyte, Covance-Bayer, AstraZeneca, Genentech, Medivation. P. Konstantinopoulos: Advisory boards: Pfizer, Merck and AstraZeneca. P.J. O'Dwyer: Research funding: GSK. All other authors have declared no conflicts of interest.