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  • American Society of Clinical Oncology (ASCO)  (17)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS5612-TPS5612
    Abstract: TPS5612 Background: ARTISTRY-7 will evaluate the novel engineered cytokine nemvaleukin alfa (nemvaleukin, ALKS 4230) in patients (pts) with gynecologic cancers. Ovarian cancer (OC) is the 8th most common cause of cancer mortality in women. OC is an area of high unmet need, as many pts become resistant/refractory to frontline platinum-based chemotherapy. In the platinum-resistant setting, standard of care chemotherapy and anti-PD-1 therapy in clinical trials have modest response rates ranging from ~6% to 20% and ~7% to 12%, respectively. Nemvaleukin was designed to selectively bind to the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating antitumor CD8 + T and natural killer cells with minimal regulatory T cell expansion. This selectivity may provide enhanced tumor killing and improved safety/tolerability vs high-dose IL-2. In clinical studies, nemvaleukin, as monotherapy and in combination with pembrolizumab, has shown clinical benefit in multiple tumor types, including OC. In ARTISTRY-1, in 14 evaluable patients with OC, 4 responses were observed with nemvaleukin + pembrolizumab, including 2 complete responses and 2 partial responses (ORR 28.6%; DCR 71.4%; median DOR 53.4 wks). Nemvaleukin monotherapy activity was also observed (6 melanoma and 4 renal cell carcinoma responses). Methods: ARTISTRY-7 (NCT05092360) is an ongoing phase 3, multicenter, randomized study of nemvaleukin and/or pembrolizumab vs chemotherapy. Eligible pts are women (≥18 y) with histologically confirmed epithelial OC (high-grade serous, endometrioid, clear cell), fallopian tube cancer, or primary peritoneal cancer. Pts must have had ≥1 prior line of systemic therapy (platinum-sensitive setting), ≤5 prior lines (platinum-resistant setting), and prior bevacizumab, with radiographic progression on most recent therapy. Pts with primary platinum-refractory disease (progression on first-line platinum therapy) or primary platinum resistance (progression 〈 3 months after first-line platinum therapy completion) are excluded. Approximately 376 pts will be randomized (3:1:1:3) to receive nemvaleukin 6 μg/kg IV (days 1-5) + pembrolizumab 200 mg IV (day 1) of each 21-day cycle, pembrolizumab or nemvaleukin monotherapy, or chemotherapy, and stratified by PD-L1 status, histologic subtype, and chemotherapy (paclitaxel vs other). Pts will continue treatment until disease progression or intolerable toxicity (maximum 35 pembrolizumab cycles; nemvaleukin can be continued). The primary endpoint is investigator-assessed PFS (RECIST v1.1) in the nemvaleukin + pembrolizumab vs chemotherapy arms. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and PK/PD effects. Clinical trial information: NCT05092360 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 2013-2013
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 3
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 11045-11045
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 11045-11045
    Abstract: 11045 Background: Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma characterized by the WWTR1- CAMTA1 fusion ( WC-F) in a majority of cases. EHE demonstrates a biphasic clinical course; remaining indolent for many years before suddenly demonstrating aggressive progression. Cell cycle mutations have been previously noted to account for some secondary alterations; however, little is known regarding the chronicity of these secondary alterations or their clinical implications. Here we present the largest assessment of secondary genomic variants and their clinical import. Methods: Comprehensive genomic profiling from 45 WC-F positive EHE patients (pts) were provided by Foundation Medicine (FMI). 8 of these 45 pts were treated at The Ohio State University (OSU) and were evaluated retrospectively through chart review. Known deleterious alterations, variants of unknown significance (VUS), and genomic copy quantification for the WC-F was included in our analysis. Targetable gene variants were defined by OncoKB. Chi-square and student’s t-tests were used as appropriate. Results: Genomic copy number of the WC-F best fit a log-normal distribution (range: 13-2,131 copies). 20 pts (44%) did not exhibit any secondary genomic variants. The most commonly altered genes included: CDKN2A/B (7 variants), RB1 (3 variants), and ATRX (3 variants). Commonly identified pathways included: cell cycle (9 pts, 20.0%), epigenetic modulators (7 pts, 15.6%), and DNA damage repair (7 pts, 15.6%). Eight pts exhibited targetable gene variants (18%) as defined by OncoKB. Subjects ≥50 years of age exhibited a greater proportion of clinically targetable variants (27.6% vs 0%; p = 0.02). Pts with a secondary genomic variant exhibited elevated WC-F copy numbers (p 〈 0.001). OSU pts with aggressive EHE were more likely to have a second genomic variant (80% vs 0%; p = 0.03) when compared to indolent EHE, with trends toward higher WC-F copy numbers (809±315 vs 207±147; p = 0.2) and older age at diagnosis (59.5±5.5 vs 36.7±8.8; p = 0.1). Conclusions: In this study, secondary genomic variants in WC-F driven EHE are more common in older patients ( 〉 50 yo). Further, the presence of secondary genomic variants is associated with an aggressive phenotype and may drive poor prognosis. Prospective research is needed to confirm these findings.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 746-746
    Abstract: 746 Background: Pelareorep is a proprietary formulation of live, replication-competent, naturally occurring Reovirus Type 3 Dearing strain. A randomized phase II trial of pelareorep in combination with carboplatin and paclitaxel in first-line treatment of metastatic PDAC (NCT01280058) was performed. Although pelareorep did not improve the primary endpoint of progression-free survival compared to carboplatin and paclitaxel alone, impressive durable responses were seen in the pelareorep arm in some patients (pts). Further, prior studies have noted the immunomodulatory carcinoembryonic antigen-related cell adhesion molecule (CEACAM6/CD66c) as a receptor for specific viral subtypes. We thus speculated that altered CEACAM6 levels may be predictive for pelareorep sensitivity. Methods: Pre-treatment tissue biopsies were collected prior enrolment for all 73 pts on study. Evaluable pts with transcriptomic data was available for only 31 pts. RNA was purified from FFPE tissue and gene expression analysis was performed using SensationPlus FFPE Amplification and WT labelling kit and the Human Transcriptome Array 2.0. CEACAM6 protein expression was determined by immunohistochemistry. Differential gene expression and survival analysis using were performed in R/Bioconductor. Appropriate corrections for multiplicity were performed. Results: When comparing extraordinary responders in the pelareorep treated arm to those with poor outcomes, low levels of CEACAM6 mRNA expression were associated with prolonged PFS in pelareorep-treated pts (adjusted p = 0.05). This effect was not seen in non-pelareorep treated pts. The luminal, but not the cytoplasmic immunohistochemistry score, was highly correlated with mRNA expression levels of CEACAM6, p = 0.001. Modulation of CEACAM6 in vitro and in vivo are underway. Conclusions: CEACAM6 may be a candidate biomarker of sensitivity to pelareorep and, in theory, could improve viral trafficking of this compound in tumor cells. Clinical trial information: NCT01280058 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS5609-TPS5609
    Abstract: TPS5609 Background: ARTISTRY-7 will evaluate the novel engineered cytokine nemvaleukin alfa (nemvaleukin, ALKS 4230) in pts with gynecologic cancers. Epithelial ovarian cancer (OC) is the 7th most common cause of cancer mortality in women. OC is an area of high unmet need, as many pts become resistant or refractory to frontline platinum-based chemotherapy. Nemvaleukin was designed to selectively bind to the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating and expanding antitumor CD8 + T and NK cells with minimal expansion of T regs . This selectivity may provide enhanced tumor killing and improved safety/tolerability compared with high-dose IL-2. In clinical studies, nemvaleukin, as monotherapy and in combination with pembrolizumab, has shown evidence of clinical benefit in multiple tumor types, including OC. In ARTISTRY-1, 4 responses were observed in pts with OC, including 2 complete responses, 1 in a pt with platinum-resistant OC and 5 prior lines of therapy, and 2 partial responses. Methods: ARTISTRY-7 is a phase 3, multicenter, open-label randomized study of nemvaleukin and/or pembrolizumab vs chemotherapy. Eligible pts are women (≥18 y) with histologically confirmed epithelial OC (high-grade serous, endometrioid, clear cell), fallopian tube cancer, or primary peritoneal cancer. Pts must have received ≥1 prior line of systemic therapy in the platinum-sensitive setting, ≤5 prior lines in the platinum-resistant setting, and prior bevacizumab, with radiographic progression on most recent therapy. Primary platinum-refractory disease (progression on first-line platinum therapy) or primary platinum resistance (progression 〈 3 months after completion of first-line platinum therapy) is exclusionary. Pts must have ECOG performance status of 0 or 1, estimated life expectancy of ≥3 months, and adequate hematologic reserve and hepatic and renal function. Approximately 376 pts will be randomized (3:1:1:3) to receive nemvaleukin 6 μg/kg IV on days 1-5 and pembrolizumab 200 mg IV on day 1 of each 21-day cycle, pembrolizumab monotherapy, nemvaleukin monotherapy, or chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan, or gemcitabine) and stratified according to PD-L1 status, histologic subtype (high-grade vs non–high-grade serous), and chemotherapy (paclitaxel vs other). Pts will continue treatment until disease progression or intolerable toxicity (maximum 35 cycles for pembrolizumab; nemvaleukin can be continued). The primary endpoint is investigator-assessed PFS (RECIST v1.1) in the nemvaleukin/pembrolizumab vs chemotherapy group. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and pharmacokinetic/pharmacodynamic effects. Clinical trial information: NCT05092360.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e16155-e16155
    Abstract: e16155 Background: Effective management of HCC needs concerted efforts of all the disciplines involved. ICI and its combinations have not improved the outcomes to the expected level outside clinical trials. This is a retrospective review of HCC patients treated with ICI in an academic institution. Methods: HCC patients who received at least one ICI dose between 1/1/2017 and 7/31/2021 at the Ohio State University were included in the study. The patient's baseline (BL) characteristics (at the first dose of ICI) were extracted with immune-related adverse events (irAE) details and survival outcomes. Descriptive statistics were used, Fisher exact test to compare categorical variables, log-rank test rank test for survival outcomes, and logistic regression model for categorical outcomes using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort has 38 patients. The median age is 67 years (range 41-88), with 82% males and 90% Caucasians (7% African American and 3% other). Refer to the table for other BL characteristics. Median overall survival (OS) and progression-free survival were 6 months (m) (95% confidence interval [CI], 4-10) and 4m (95% CI, 3-6), respectively. The OS was better in patients with longer DoT (≤ 2m vs 3-6m vs ≥6m, 2m vs 5m vs 24m, p 〈 0.001). Even though PFS was significantly better in patients with CP A-B9 (Vs B9-C, 6m vs 2.5m, p=0.03) and CP B (vs A vs C, 9m vs 5m vs 2m, p=0.02), OS was not different. Poor responders ( 〈 2 m vs ≥ 3m PFS) in this cohort had higher BL total bilirubin (TB) (p=0.03) and are more likely to have CPC (p=0.03) or CP B9-C (p=0.01) and BCLC D (p=0.04) patients. CP class (lower, p=0.0007), DoT (≥ 6m, p=0.0001), combination with bev (p=0.004), fewer liver lesions (≤2, 〈 0.001), no history of any LRT (p=0.01) or fewer LRTs (p=0.01), and non-metastatic disease (p 〈 0.001) are associated with better OS. PVTT, line of therapy, and ALBI G did not impact the OS. IrAE were reported just 4 (10%) patients. Conclusions: In this small retrospective cohort, lower volume of hepatic HCC lesions, use of ICI with bev, lower TB, longer DoT were associated with better OS, while more advanced disease, CPC, BCLC D, more LRTs and higher bilirubin resulted in worse survival. Our results suggest that prescribing ICI in line with FDA approval indications results in better outcomes. They must be validated in larger studies. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4551-4551
    Abstract: 4551 Background: Novel imaging modalities using frequently expressed RCC antigens, such as CAIX, have shown promise in early-stage disease (Shuch B et al ASCO GU 2023). In advanced RCC, no tissue-based biomarkers have been well established to predict outcome with contemporary regimens, e.g., checkpoint inhibitors (CPIs) or targeted therapy (TT). We hypothesize that functional imaging of CD8 T-cells (CD8s) with crefmirlimab (a ~80 kDA 89 Zr-labelled minibody with high affinity for CD8) may predict response given the essential role of CD8 T-cells (CD8s) in mediating CPI response. Methods: Eligible pts had pathologically verified RCC, metastatic disease and an intent to initiate standard of care CPI therapy. Patients received crefmirlimab PET/CT within 1 wk of CPI infusion and 4-6 weeks after initiating therapy. Baseline biopsy was mandated, along with repeat biopsy 0-2 weeks following the second PET/CT scan. PET signal was characterized as SUV max , SUV peak and SUV mean of the biopsied lesions, up to 5 index lesions and representative CD8 avid lymph nodes. Mean SUV max in responders and non-responders were compared using students t-test (1-sided). CD8 expression in tissue was characterized as the number of positive cells per mm 2 ; PET avidity and CD8 expression were compared using the Spearman correlation coefficient. Results: 17 pts (9 M: 8 F) were enrolled; most pts had clear cell histology (12; 71%) followed by unclassified (3; 17%) and papillary (2; 12%). The most commonly rendered CPI-based regimens were nivolumab alone (6 pts; 35%) and cabozantinib/nivolumab (3 pts; 17%). Follow-up data was available in 15 of the patients. By RECIST v1.1, 3 of 15 patients were classified as responders (best overall response [BOR] of complete response or partial response) and 12 patients were classified as non-responders (BOR of stable disease or progressive disease). Average SUV max , SUV peak and SUV mean per patient among all quantified index lesions and representative lymph nodes were 10.02, 6.95 and 6.11 for baseline and 8.82, 6.23 and 5.39 during treatment, respectively. Average SUV max at baseline was 14.68 in responders to CPI and 8.28 in non-responders (P=0.006). On treatment SUV max was 10.93 in responders to CPI and 8.22 in non-responders (P=0.19). A strong correlation between CD8 expression in baseline tissue and normalized SUV mean was observed (r=0.77; 95%CI 0.53-0.91). Conclusions: To our knowledge, this is the first series in RCC to demonstrate that functional imaging of immune cells (here, CD8s) may segregate response to CPIs, with responders having a higher baseline SUV and a larger decrement in SUV with therapy. Our results are bolstered by a significant correlation between tissue and imaging CD8 expression. Larger studies are underway to validate this noninvasive strategy. Clinical trial information: NCT03802123 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 8
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 3551-3551
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 3551-3551
    Abstract: 3551 Background: The development of non-invasive biomarkers has the potential to revolutionize clinical care for colorectal cancer (CRC) patients. The presence of bacteria in CRC tumor biopsies has been shown to contribute to CRC development. In a previous study, our group showed some intra-tumor microbes in CRC tumor biopsies correlated with overall survival in CRC patients. However, the correlations between microbes in tumor vs blood, and between non-invasive serum marker carcinoembryonic antigen (CEA) and microbes are unknown. We hypothesize that tumor microbes will also be found in blood, and that CEA will correlate with certain microbes. Methods: We obtained RNA-seq data from CRC tumor biopsies from patients treated at The Ohio State University Comprehensive Cancer Center as part of the Oncology Research Information Exchange Network (ORIEN). Reads were aligned to human and exogenous genomes using TopHat2 and Kraken2/Bracken, respectively. RNA-seq from CRC tumor biopsies as well as peripheral blood at the Cancer Genome Atlas (TCGA) consortium were processed by the same method. Results: The analyzed ORIEN cohort included 93 CRC patients with an age range from 30-83 years, 60.2% male, 87.1% adenocarcinoma, and 47.3% with metastatic CRC. The TGCA cohort included 495 CRC patients with an age range from 31-90 years, 53.3% male, 85.1% adenocarcinoma, and 15.5% with metastatic CRC. Over fifteen exogenous phyla (including bacteria, viruses, fungi) were observed in both ORIEN and TCGA cohorts. Several of the samples were dominated by viral sequences while others by bacteria, suggesting considerable tumor microbiome heterogeneity. Evaluation of the fraction of microbes in tumor and blood showed that nearly all the microbes found in blood (97.6%) were also observable in tumor in the TCGA cohort. Microbial abundances of various taxa, including Fusobacterium, significantly correlated between blood and tumor. Several bacteria including members of the genera Bacillus and Staphylococcus were positively associated with tumor stage (metastatic vs non-metastatic), but microbial relative abundances were not correlated with the location of tumor in colon (right, left, transverse colon). Certain microbial species from the ORIEN cohort were found to positively correlate with CEA, (including from the genera Fusobacterium, Lactobacillus, Pseudomonas, Vibrio, Clostridium) and these associations remained when adjusted for alcohol and smoking by multivariate analysis. Conclusions: Nearly all the microbes found in blood were found in tumor and abundances of various taxa were significantly correlated, suggesting that blood-based cancer microbiome analysis has great potential. Serum CEA has a low diagnostic ability when used alone, but combining this with blood microbiome could improve diagnostic/prognostic utility as a non-invasive biomarker.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 9
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e17633-e17633
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e17633-e17633
    Abstract: e17633 Background: For patients with endometrial cancer, the PI3K/AKT/mTOR pathway is an attractive target due to dysregulation of the pathway secondary to commonly found genetic alterations. Previous trials of mTOR inhibitors in endometrial cancer have shown modest clinical activity and tolerability. Here we present a proteomics based approach to identify novel partners that will enhance the efficacy of dual TORC1/2 inhibition. Methods: Five endometrial cell lines (AN3CA, ECC, HEC1A, HEC1B, RL952) were treated with the TORC1/2 inhibitor TAK228 or vehicle for one hour and protein concentrations were analyzed by reverse phase protein arrays (RPPA). We examined baseline protein and changes in individual proteins after treatment with TAK228 to determine correlations with sensitivity to TAK228. Identified proteins were then targeted with single agent pharmacologic inhibition and cytotoxicity measured by XTT analysis. Target inhibition was validated using WB analysis. Cooperativity in cytotoxicity for relevant combinations was measured using the methods of Chou-Talalay. Other phenotypic endpoints including migration, cell cycle alterations by flow cytometry and cell growth using live cell imaging were also collected. Results: Based on proteomics analysis, altered phosphorylation of CHK1(S296), CHK2(T68) and increasing concentration of VEGFR2 were strongly correlated with TAK228 resistance. TAK228 (TORC1/2, IC50 4-20nM), AZD7762 (CHK1/2, IC50 15-160nM), LY2603618 (CHK1, IC50 260nM-7.5mM) and cediranib (VEGFR2, 800nM-1mM) all had significant cytotoxic effects as individual agents on multiple endometrial cell lines. AZD7762 in combination with TAK228 led to synergism in all cell lines tested (mean combination index, 0.2-0.8). Single agent AZD7762 increased the number of cells in S-Phase and decreased cellular migration. Addition of recombinant VEGF-A to cell culture enhanced resistance to TAK228 in a dose dependent manner as measured by cell growth assays using live cell imaging. Combination of cediranib and TAK228 also showed significant synergism in multiple cell lines. Conclusions: RPPA identified changes in phosphorylated CHK1/2 and total VEGFR2 as being correlated to resistance to dual TORC1/2 inhibition with TAK228 in multiple endometrial cancer cell lines. While single agent activity of TORC1/2, CHK1/2 and VEGFR2 inhibitors showed varying activity, combinations of TAK228 with either cediranib or AZD7762 showed significant synergism in multiple cell lines. Clinical examination of these combinations agents may prove useful in recurrent endometrial cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e16032-e16032
    Abstract: e16032 Background: There are no established risk factors or toxicity biomarkers for ECs and GCs treated with ICI, even though they are commonly used in current clinical practice. Additionally, the predictive value of programmed death-ligand 1 (PDL1) expression level is questionable. This is a retrospective review of patients with EC or GC treated with ICI at an academic institute to identify RF for poor outcomes. Methods: Patients with EC or GC who received at least one dose of ICI for Stage IV or recurrent disease between 1/1/2015 and 7/31/2021 at the Ohio State University were included in the study. The patients' baseline (BL) characteristics (at the first dose of ICI) were extracted with immune-related adverse events (irAE) details and survival outcomes. Descriptive statistics, Fisher exact test for categorical variables, log-rank test for survival outcomes, and logistic regression modeling for categorical outcomes were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort included 67 patients (42 EC and 25 GC). The median age was 65 years (range 33-90) with 84% male, 88% Caucasian (4% African American & 8% others), and 93% with distant metastasis (7% recurrent disease). 75% received the first ICI dose in ≥ 3 lines with 4% first line, 41% had a history of radiotherapy (XRT) (22% palliative & 19% neoadjuvant [NA]), and only 9% had chemotherapy combination (CC). Most were microsatellite stable (90%), and PDL1 expression was not available in 39%, negative in 7%, and positive in 53%. Median overall survival (OS) and progression-free survival (PFS) were 5 months (m) (95% confidence interval [CI] , 2-8) and 3m (95% CI, 2-4), respectively. Patients with ICI in ≥ 3 lines did worse (vs ≤ 2 lines, 3m vs 12m, respectively, p = 0.01) in OS. Patients with a history of XRT had lower PFS (yes vs no, 2m vs 3m, p = 0.02), but OS was not significantly different. BL white cell count (WBC) (p = 0.002), alkaline phosphatase (ALP) (p = 0.006), total bilirubin (TB) (p = 0.004), thyroid stimulating hormone (TSH) (p = 0.04), and free T4 (p = 0.01) significantly impacted OS, while WBC (p = 0.01), red cell count (RBC) (p = 0.02), platelet count (PLC) (p = 0.04), and absolute lymphocyte count (ALC) (p = 0.01) impacted PFS. RFs positively related to OS and PFS were the line of ICI and CC, while high ALP and prior XRT were negatively related to OS and PFS. Low albumin (p = 0.003) was negatively related to OS-only while primary tumor location (EC, p = 0.04) and prior NA XRT (p = 0.01) were negatively related to PFS-only. Other BL characteristics, including PDL-1 expression (among patients with available values), did not impact outcomes. Only 7% (n = 5) had irAE, and two had ≥ grade 3. Conclusions: Patients with identified RFs (EC primary, prior XRT, NA XRT, and BL labs such as WBC, RBC, PLC, ALP, ALC, albumin, TB, TSH, and free T4) for clinical outcomes should be monitored closely. These associations should be confirmed in larger studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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