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PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1/2 mutations treated with talazoparib are reported. METHODS: Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Patients with germline BRCA -mutated human epidermal growth factor receptor 2–negative locally advanced or metastatic breast cancer were not eligible for this study. Primary end point was disease control (DC) determined by investigator assessment of objective response (OR) or stable disease (SD) of at least 16 weeks duration (SD16+). The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = 0.82; α =.10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS: Twenty-eight patients (20 cancer types) with BRCA1/2 mutations were enrolled from December 2019 to September 2021 and collapsed into a single histology pooled cohort for analysis. All patients were evaluable for efficacy. One complete response, nine partial response, and six SD16+ were observed for DC and OR rates of 57% (one-sided 90% CI, 43 to 100) and 36% (95% CI, 19 to 56), respectively. The null hypothesis of a 15% DC rate was rejected (P <.001). Patients with OR had the following tumor types: breast (2), nonmelanoma skin, mesothelioma, stomach, uterus, non–small cell lung cancer, ovary, hepatocellular carcinoma, and pancreas. Thirteen patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to talazoparib. All were consistent with the drug label except bilirubin increase and hyponatremia (both grade 3 AEs). CONCLUSION: Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration–approved. Talazoparib showed activity in patients with BRCA-mutated tumors for which PARP inhibitors are not yet FDA-approved. @ASCO #TAPUR [ABSTRACT FROM AUTHOR]

PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results from cohorts of patients with metastatic breast cancer (BC) with FGFR1 and FGFR2 alterations treated with sunitinib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Forty patients with BC with FGFR1 (N = 30; amplification only n = 26, mutation only n = 1, both n = 3) or FGFR2 (N = 10; amplification only n = 2, mutation only n = 6, both n = 2) alterations were enrolled. Three patients in the FGFR1 cohort were not evaluable for efficacy; all patients in the FGFR2 cohort were evaluable. For the FGFR1 cohort, two patients with partial response and four with SD16+ were observed for DC and OR rates of 27% (90% CI, 13 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected (P =.169). No patients achieved DC in the FGFR2 cohort (P = 1.00). Thirteen of the 40 total patients across both cohorts had at least one grade 3-4 adverse event or serious adverse event at least possibly related to sunitinib. CONCLUSION: Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either FGFR1 or FGFR2 alterations. Other treatments and clinical trials should be considered for these patient populations. Sunitinib did not demonstrate antitumor activity in patients with FGFR1-/2-amplified or -mutated breast cancer. @ASCO #TAPUR [ABSTRACT FROM AUTHOR]

PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with lung cancer and ERBB2 mutation or amplification treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients had advanced lung cancer of any histology, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2 mutation or amplification. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) per RECIST v. 1.1 or stable disease (SD) of at least 16 weeks duration (SD16+). Secondary end points included safety, duration of response, duration of SD, progression-free survival, and overall survival. RESULTS: Twenty-eight patients with lung cancer (27 non–small-cell, 1 small-cell) and ERBB2 mutation (n = 15), ERBB2 amplification (n = 12), or both (n = 1) were enrolled from November 2016 to July 2020. All patients were evaluable for efficacy and toxicity. Three patients with partial response (two ERBB2 mutation; one both mutation and amplification) and seven patients with SD16+ (five ERBB2 mutation; two amplification) were observed for a DC rate of 37% (95% CI, 21 to 50; P =.005) and OR rate of 11% (95% CI, 2 to 28). Five patients had one or more grade 3 or 4 adverse or serious adverse events at least possibly related to P + T. CONCLUSION: Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non–small-cell lung cancer and ERBB2 mutation or amplification, particularly those with ERBB2 exon 20 insertion mutations. Pertuzumab + trastuzumab had antitumor activity in pretreated patients with ERBB2-mutated NSCLC @ASCO #TAPUR. [ABSTRACT FROM AUTHOR]

PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non–small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported. METHODS: Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon's two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting. CONCLUSION: Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population. [ABSTRACT FROM AUTHOR]

We have previously demonstrated an association between microsatellite instability and decreased CDK2-AP1 (p12DOC-1) expression in human colorectal cancer (CRC) cell lines. In those same studies, induction of CDK2-AP1 expression promoted both cell cycle arrest and apoptosis. The goals of our present study were to better understand the mechanisms leading to reduced CDK2-AP1 expression in microsatellite unstable (MSI) CRC and to study further the effect of CDK2-AP1 modulation on cell proliferation and apoptosis utilizing RNA interference (RNAi) techniques. We used direct sequencing to screen for mutations of the poly (T)8 microsatellite-like region in the 3'end of the CDK2-AP1 gene in 24 CRC cell lines. We then utilized an in vitro human mismatch repair (MMR) recombinant system to assess for correction of the mutation and changes in CDK2-AP1 expression secondary to hMLH1 transfection. We also investigated the effect of CDK2-AP1 modulation in four settings: (1) native CDK2-AP1 absence, (2) endogenous CDK2-AP1 expression, (3) RNAi-induced CDK2-AP1 inhibition and (4) induced CDK2-AP1 over expression. The mutation-del T poly (T)8-at the 3'end of the CDK2-AP1 gene was found in 3/12 (25%) of MSI CRC cell lines, but in none of the microsatellite stable samples (0/12). Interestingly, when wild-type MMR protein-MLH1-was induced in an in vitro human recombinant system, the del T poly (T)8 mutation was reversed and CDK2-AP1 expression increased. RNAi-mediated CDK2-AP1 inhibition was associated with decreased apoptosis and increased cell proliferation in CDK2-AP1-non deficient CRC cell lines. We conclude that mutations in the microsatellite-like sequence of the CDK2-AP1 gene in MSI CRC are associated with decreased CDK2-AP1 expression. In addition, modulation of CDK2-AP1 expression in human CRC alters cell proliferation and apoptosis.Oncogene (2005) 24, 3657-3668. doi:10.1038/sj.onc.1208378 Published online 4 April 2005 [ABSTRACT FROM AUTHOR]

Background: The burden of early onset colorectal cancer (EOCRC) falls disproportionately on minorities and individuals in specific geographic regions. While these disparities are likely multi-factorial, access to high-quality health care plays a significant role. We sought to determine if Medicaid expansion is associated with reducing racial disparities in EOCRC detection in Hispanics and non-Hispanic Blacks (NHB), compared to non-Hispanic Whites (NHW)., Methods: Analysis of data from National Cancer Database was undertaken to compare incidence of EOCRC among those aged 40-49 between Medicaid expansion states (ES) and non-expansion states (NES) by racial/ethnic groups. Data was classified by race (NHW, NHB, or Hispanic), state of residence (ES or NES), and time (pre- or post-expansion). The primary outcome was change in incidence rate of EOCRC among racial/ethnic groups, according to whether patients resided in Medicaid expansion or non-expansion states., Results: Among Hispanics, the ES showed a significant increase in EOCRC incidence post expansion as compared to NES (p = 0.03). The rate of increase in annual incidence of EOCRC among Hispanics was 4.3% per year (pre-expansion) and 9.8% (post-expansion) for ES; and 6.4% (pre-expansion) and 1% (post-expansion) in NES. However, no difference was noted among NHB (p = 0.33) and NHW (p = 0.94)., Conclusions: Medicaid expansion has improved detection rates of EOCRC in ES especially in Hispanic population. This is the first study to demonstrate the effect of Medicaid expansion on the incidence of EOCRC. Based on our study findings we suggest that racial and ethnic disparities should be considered in the earlier CRC screening debates., (© 2023. W. Montague Cobb-NMA Health Institute.)

Background: Breast cancer is the most common cancer in the United States and the second leading cause of death for American Indian women. American Indian women have lower rates of breast cancer screening than other racial groups, and disparities in breast cancer mortality and survival rates persist among them. To address this critical need, a culturally appropriate, accessible, and personalized intervention is necessary to promote breast cancer screening among American Indian women. This study used mobile health principles to develop a mobile web app-based mammogram intervention (wMammogram) for American Indian women in a remote, rural community in the Northern Plains., Objective: This study aimed to assess the feasibility and efficacy of the wMammogram intervention, which was designed to motivate American Indian women to undergo breast cancer screening, as compared with the control group, who received an educational brochure., Methods: Using community-based participatory research (CBPR) principles and a multipronged recruitment strategy in a randomized controlled trial design, we developed the wMammogram intervention. This study involved 122 American Indian women aged between 40 and 70 years, who were randomly assigned to either the intervention group (n=62) or the control group (n=60). Those in the intervention group received personalized and culturally appropriate messages through a mobile web app, while those in the control group received an educational brochure. We measured outcomes such as mammogram receipt, intention to receive breast cancer screening after the intervention, and participants' satisfaction with and acceptance of the intervention., Results: A significantly higher proportion of women who received the wMammogram intervention (26/62, 42%; P=.009) completed mammograms by the 6-month follow-up than the control group (12/60, 20%). The wMammogram intervention group, compared with the control group, reported significantly higher ratings on perceived effectiveness of the intervention (t 120 =-5.22; P<.001), increase in knowledge (t 120 =-4.75; P<.001), and satisfaction with the intervention (t 120 =-3.61; P<.001). Moreover, compared with the brochure group, the intervention group expressed greater intention to receive a mammogram in the future when it is due (62/62, 100% vs 51/60, 85%) and were more willing to recommend the intervention they received to their friends (61/62, 98.4% vs 54/60, 90%) with statistically significant differences., Conclusions: This study shows the feasibility and efficacy of the wMammogram intervention to promote breast cancer screening for American Indian women in a remote, rural community-based setting. Findings suggest that, with advancements in technology and the ubiquity of mobile devices, mobile web apps could serve as a valuable health intervention tool that builds upon low-cost technology and enhances accessibility and sustainability of preventive care to help reduce breast health disparities experienced in hard-to-reach American Indian populations., Trial Registration: ClinicalTrials.gov NCT05530603; https://clinicaltrials.gov/ct2/show/NCT05530603., (©Soonhee Roh, Yeon-Shim Lee, DenYelle B Kenyon, Amy J Elliott, Daniel G Petereit, Anu Gaba, Hee Yun Lee. Originally published in JMIR Formative Research (https://formative.jmir.org), 20.07.2023.)

Introduction: Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care., Materials and Methods: Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes., Results: A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration-approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen., Conclusion: A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.

The most common causes of focal brain lesions (FBLs) in patients with HIV infection are cerebral toxoplasmosis, primary central nervous system lymphoma (PCNSL), and progressive multifocal leukoencephalopathy. Neoplasms other than PCNSL are uncommon. We report a rare case of metastatic carcinoma causing an FBL in a patient with HIV infection. The diagnostic workup and further management of FBLs in HIV are outlined in this review. The standard approach includes a lumbar puncture and cerebrospinal fluid (CSF) analysis for cytology and Epstein-Barr virus (EBV) DNA testing by polymerase chain reaction. Empiric therapy for PCNSL is justifiable for patients with positive CSF EBV-DNA test results and a positive single-photon emission computed tomography (SPECT) scan, especially if there has been no response to antitoxoplasmosis therapy. Brain biopsy may be indicated, however, in select cases that do not meet these criteria in order to identify potentially treatable infections and PCNSL.