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  • 1
    Online Resource
    Online Resource
    Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 31 ( 2020-11-01), p. 3672-3684
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 31 ( 2020-11-01), p. 3672-3684
    Abstract: We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.01652
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Cabozantinib plus Nivolumab Phase I Expansion Study in Patients with Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy
    American Association for Cancer Research (AACR) ; 2022
    In:  Clinical Cancer Research Vol. 28, No. 7 ( 2022-04-01), p. 1353-1362
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 7 ( 2022-04-01), p. 1353-1362
    Abstract: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI). Patients and Methods: A phase I expansion cohort of patients with mUC who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.1.1. Secondary objectives included progression-free survival (PFS), duration of response (DoR), overall survival (OS), safety, and tolerability. Results: Twenty-nine out of 30 patients enrolled were evaluable for efficacy. Median follow-up was 22.2 months. Most patients (86.7%) received prior chemotherapy and all patients received prior CPI (median seven cycles). ORR was 16.0%, with one complete response and three partial responses (PR). Among 4 responders, 2 were primary refractory, 1 had a PR, and 1 had stable disease on prior CPI. Median DoR was 33.5 months [95% confidence interval (CI), 3.7–33.5], median PFS was 3.6 months (95% CI, 2.1–5.5), and median OS was 10.4 months (95% CI, 5.8–19.5). CaboNivo decreased immunosuppressive subsets such as regulatory T cells (Tregs) and increased potential antitumor immune subsets such as nonclassical monocytes and effector T cells. A lower percentage of monocytic myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear MDSCs, lower CTLA-4 and TIM-3 expression on Tregs, and higher effector CD4+ T cells at baseline were associated with better PFS and/or OS. Conclusions: CaboNivo was clinically active, well tolerated, and favorably modulated peripheral blood immune subsets in patients with mUC refractory to CPI.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-21-3726
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 3
    Online Resource
    Online Resource
    Ipilimumab challenge/re-challenge in metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors treated with cabozantinib+nivolumab (CaboNivo) or cabozantinib+nivolumab+ipilimumab (CaboNivoIpi).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 5039-5039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5039-5039
    Abstract: 5039 Background: We investigated challenging/re-challenging pts with ipilimumab (ipi) after progression on CaboNivo or CaboNivoIpi. Methods: In a phase I expansion study, patients with mUC post-platinum chemotherapy and other GU tumors patients who progressed on Cabo 40 mg daily plus nivolumab, 3 mg/kg every 21 days (CaboNivo) alone or with ipi, 1 mg/kg every 21 days for 4 cycles (CaboNivoIpi)-and achieved a PR or SD≥6 mo, were challenged/re-challenged with ipi, 1 mg/kg every 21 days for up to 4 cycles. Restaging scans were done every 6 wks for the first 12 wks, then every 8 wks and evaluated by RECIST 1.1. Results: In total, 24 patients were evaluated: 18 pts (8 UC (5 bladder and 3 upper tract), 4 clear cell renal cell carcinoma (RCC), 3 urachal adenocarcinoma (adeno), 2 bladder adeno, and 1 sarcomatoid clear cell RCC) who progressed on CaboNivo were challenged with ipi. In the challenge group, median (m) follow-up was 21.2 months. One pt achieved a PR in the LNs, but was found to have brain metastases before the next restaging, 13 had SD and 4 had PD. Median duration of PR or SD was 3.6 months (95% CI: 1.4 – 7.8 months). The mOS from start of ipi challenge was 13.9 months (95% CI: 5.8 months- not estimable); mPFS was 4.6 months (95% CI: 1.9 – 8.7 months). Grade 1/2 treatment related adverse events (AEs) occurred in all 18 pts (100%) and ≥Grade 3 (G≥3) AEs occurred in 11 pts (61%). The most common G≥3 AEs were hypophosphatemia (22%), hypertension (6%), adrenal insufficiency (6%), increased AST (6%), and ALT (6%). Six patients (3 bladder UC, 1 penile squamous cell (SCC) carcinoma, 1 urethral SCC, and 1 clear cell RCC with sarcomatoid features) who progressed on CaboNivoIpi were re-challenged with Ipi. On re-challenge, mfollow-up was 20.9 months. There were no PRs, 3 SDs and 3 PDs. mOS from start of re-challenge was 4.0 months (95% CI: 2.2 – 23.3 months) and mPFS was 1.9 months (95% CI: 1.1 – 2.6 months). Grade 1/2 treatment related AEs occurred in all 6 pts (100%) and ≥Grade 3 (G≥3) AEs occurred in 2pts (33%). G≥3 AEs included 1 hypertension (17%) and 1 hyperphosphatemia (17%). Conclusions: Ipi challenge/re-challenge showed low response rates in pts previously treated with CaboNivo or CaboNivoIpi. However, pts treated with CaboNivo who were challenged with ipi had a better OS than patients who had progressed on CaboNivoIpi and were re-challenged with ipi. Larger trials are warranted testing the ipi challenge in pts progressing on CaboNivo. Clinical trial information: NCT02496208 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.5039
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Highlights of the society for immunotherapy of cancer (SITC) 27th annual meeting
    BMJ ; 2013
    In:  Journal for ImmunoTherapy of Cancer Vol. 1, No. 1 ( 2013-12)
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 1, No. 1 ( 2013-12)
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1186/2051-1426-1-4
    Language: English
    Publisher: BMJ
    Publication Date: 2013
    detail.hit.zdb_id: 2719863-7
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  • 5
    Online Resource
    Online Resource
    The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19
    American College of Physicians ; 2022
    In:  Annals of Internal Medicine Vol. 175, No. 10 ( 2022-10), p. 1401-1410
    Details
    In: Annals of Internal Medicine, American College of Physicians, Vol. 175, No. 10 ( 2022-10), p. 1401-1410
    Type of Medium: Online Resource
    ISSN: 0003-4819 , 1539-3704
    URL: Article
    DOI: 10.7326/M22-0924
    RVK:
    XA 23600
    Language: English
    Publisher: American College of Physicians
    Publication Date: 2022
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  • 6
    Online Resource
    Online Resource
    Phase I expansion study of cabozantinib plus nivolumab (CaboNivo) in metastatic urothelial carcinoma (mUC) patients (pts) with progressive disease following immune checkpoint inhibitor (ICI) therapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 5037-5037
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5037-5037
    Abstract: 5037 Background: Previous treatment with ICI is more common in clinical practice since recent FDA-approval of 5 ICIs in second-line and 2 in first-line for mUC. There is lack of data regarding the use of ICI after progression on a prior ICI. Cabozantinib has been shown to have immunomodulatory properties and may have synergistic effect with ICI. Methods: This is a phase I expansion cohort of mUC pts, who received prior ICI, treated with Cabozantinib 40mg daily and Nivolumab 3mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary objective was to determine the efficacy and tolerability of CaboNivo. Results: Twenty-nine mUC pts were treated. Median follow-up was 14.1 months (mo). The majority of pts were male (75.8%); 27 were White (93.1%), and 2 were Asian (6.9%). Primary tumor was bladder in 21 pts (72.4%) and upper tract in 8 (27.6%). Twenty-two pts (75.9%) had visceral metastasis (mets), 4 (13.8%) had lymph node only mets and 13 (44.8%) had liver mets. The median number of prior lines of treatment for mUC was 2 (range 0-8) with 17 pts (58.6%) receiving 2 prior lines of treatment. The majority of pts (86.2%) received prior chemotherapy for mUC and all pts received prior ICI. The median number of cycles of prior ICI was 7 (range 1-20) and median time between previous ICI and CaboNivo was 2.5 mo (range 1-18). The best response to previous ICI was partial response (PR) in 1 pt (3.4%), stable disease (SD) in 13 (44.9%), progressive disease (PD) in 14 (48.3%) and one (3.4%) was not evaluable (NE). The overall response rate for CaboNivo was 13.8% with 4 pts achieving PR (13.8%), 15 SD (51.7%), 7 PD (24.2%) and 3 NE (10.3%). Responses were seen in the liver, lung, and lymph nodes. Among 4 pts with PR, 2 were primary refractory to previous ICI and 2 had SD. At cutoff date the median duration of response was not reached and 3 PR were still ongoing: 1 had just began and the other 2 were ongoing at 12.3 and 26.4 mo. Among 15 pts with SD, 4 had SD for more than 6 mo and 2 were still ongoing at 8.1 and 25.1 mo. Median progression-free survival was 3.6 mo (95% CI: 2.1 – 5.3 mo) and median overall survival was 10 mo (95% CI: 5.8 – 16.7 mo). Grade 1/ 2 treatment related adverse events (AEs) occurred in 28 pts (97%) and 〉 Grade 3 (G 〉 3) AEs occurred in 14 pts (48%). The most common G 〉 3 AEs were fatigue (14%), hypophosphatemia (14%), lymphocyte count decrease (14%), hypertension (7%) and hyponatremia (7%). Conclusions: CaboNivo is clinically active and safe in heavily pretreated pts with progressive mUC following ICI. Clinical trial information: NCT02496208 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.5037
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    A phase I study of cabozantinib plus nivolumab (CaboNivo) and ipilimumab (CaboNivoIpi) in patients (pts) with refractory metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 6_suppl ( 2017-02-20), p. 293-293
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 293-293
    Abstract: 293 Background: We report the safety and clinical activity of CaboNivo and CaboNivoIpi in pts with mUC and other GU tumors. Methods: Part I included 4 dose levels (DLs) (Cabo PO daily and Nivo IV q2wk): DL1 Cabo40/Nivo1, DL2 Cabo40/Nivo3, DL3 Cabo60/Nivo1, DL4 Cabo 60/Nivo3. Part II included 3 DLs (Cabo PO daily, plus NivoIpi IV q3 wk x 4 doses then Nivo q2wk): DL5 Cabo 40/Nivo1/Ipi1, DL6 Cabo40/Nivo3/Ipi1, DL7 Cabo 60/Nivo3/Ipi 1. Tumors were assessed for overall response rate (ORR) by RECIST 1.1. Adverse events (AEs) were graded (G) by NCI-CTCAE v4.0. Results: From 7/22/15-10/14/16, 40pts [mUC N=14/(plasmacytoid N=1); bladder urachal N=4; bladder squamous cell carcinoma (bSCC) N=2; germ cell tumor (GCT) N=4; castrate-resistant prostate cancer (CRPC) N=9/(neuroendocrine prostate N=1); sarcomatoid renal cell carcinoma (sRCC) N=1; trophoblastic tumor N=1); sertoli cell tumor N=1; and penile SCC N=4] were treated. Median age was 58 (range 31-77); 36 (90%) were male. AEs related to study drugs with [1] CaboNivo included G3 hyponatremia 4/24 (17%), hypophosphatemia 4/24 (17%), lipase increase 3/24 (13%), dehydration 2/24 (8%), diarrhea 2/24 (8%), fatigue 2/24 (8%), HTN 2/24 (8%), thromboembolic event 1/24 (4%), rash 1/24 (4%), chest pain 1/24 (4%), amylase increase 1/24 (4%), hyperthyroid 1/24 (4%), proteinuria 1/24 (4%), thrombocytopenia 1/24 (4%); and G4 pyelonephritis 1/24 (4%); [2] CaboNivoIpi included G3 hypophosphatemia 2/16 (13%), lipase increase 2/16 (13%), fatigue 1/16 (6%), ALT increase 1/16 (6%), and HTN 1/16 (6%). There were 2/40 (5%) G3 immune-related AEs: 1 aseptic meningitis/CaboNivo; and 1 colitis/CaboNivoIpi. There were no G5 toxicities, or DLTs. 38 pts were evaluable for response. ORR was 12/38 (32%): 1 CR (bSCC); 11 PRs (5 mUC, 1 sRCC, 1 urachal, 1 bSCC, 1 CRPC, 2 penile). SD 20/38 (53%); 9/11 responses were ongoing and 26/39 (67%) pts remain on study. Conclusions: CaboNivo and CaboNivoIpi were well tolerated with no DLTs. Responses were seen at all DLs. The recommended dose for Part I is Cabo40/Nivo3 and for Part II is Cabo40/Nivo3/Ipi1. Rare tumors such as bSCC, urachal, and penile cancer demonstrated responses. Clinical trial information: NCT02496208.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.6_suppl.293
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Melanoma: A model for testing new agents in combination therapies
    Springer Science and Business Media LLC ; 2010
    In:  Journal of Translational Medicine Vol. 8, No. 1 ( 2010-12)
    Details
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2010-12)
    Type of Medium: Online Resource
    ISSN: 1479-5876
    URL: Article
    DOI: 10.1186/1479-5876-8-38
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2118570-0
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  • 9
    Online Resource
    Online Resource
    A phase II basket trial of dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART) SWOG S1609: The vulvar cancers.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 5517-5517
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 5517-5517
    Abstract: 5517 Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be effective in several malignancies but their potential role in various rare solid cancers is yet to be established. The efficacy of immunotherapy in vulvar cancer patients has not been explored. This study presents the first results of ipilimumab and nivolumab in vulvar cancers (cohort 35) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)); progression-free survival (PFS), overall survival (OS), stable disease (SD) 〉 6 months, and toxicity are secondary endpoints. Results: Sixteen evaluable patients (median age, 55.5 years) were analyzed. 14 cases were of squamous cell carcinoma histology and 2 were of poorly differentiated carcinoma. ORR was 18.8% (3/16, 25% when including one unconfirmed PR). There was 1 CR (SCC; PFS of 465 days) and 2 PR (both SCC; one with 57% regression with PFS of 1022 days, another with 53% regression with PFS of 501 days). Of note, there was one SCC patient with unconfirmed PR that showed 69% regression with PFS of 209 days. Overall clinical benefit rate (CBR; no progression 〉 6months) was 31.3% (5/16). The median PFS was 2.2 months, 6-month PFS 33%, 1-year PFS 20%. The median OS was 7.6 months, 6-month OS 62%, 1-year OS 44%. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n = 4 each). Grade 3-4 adverse events occurred in 25% of patients (n = 4). There was 1 grade 3-4 adverse event (6.7%) that led to discontinuation, and 1 (6.7%) grade 5 death adverse event. Conclusions: Ipilimumab plus nivolumab in vulvar cancers resulted in an ORR of 18.8% and CBR of 31.3%, with durable responses seen. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies exploring the role of immunotherapy in vulvar cancers are warranted. Clinical trial information: NCT02834013 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.5517
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
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    A Lasso Cox score consisting of CTLA4 + regulatory T cells (Treg), monocytic myeloid derived suppressor cells (M-MDSC), and CXCR3 + CD8 + T cells: Association with adjuvant ipilimumab (ipi) survival outcomes in patients (pts) with high-risk melanoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e21557-e21557
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e21557-e21557
    Abstract: e21557 Background: High-risk melanoma pts treated with ipi had a more favorable outcome than those treated with interferon-α2b (IFN) in phase III adjuvant trial E1609. We hypothesized that further profiling of circulating immune cells and cytokines would inform underlying mechanisms associated with immune response vs. resistance to CTLA4 blockade. Methods: Multiparameter flow cytometry was used to compare surface protein expression on PBMC collected at baseline, focusing on Treg, MDSC and effector T cells (N = 210 ipi, N = 119 IFN). Multiplex Luminex assays were used to test baseline serum for concentrations of candidate cytokines, chemokines and growth factors. A survival analysis tool, DRPPM-PATH-SURVEIOR, was then used to perform a univariate screening of these analytes using a Cox proportional hazards (PH) model. A median cut-point was derived for each marker, and pts were split into above or below median cohorts. The dichotomized scores were then processed through a Cox regression analysis. Features were ranked based on p-values calculated by a likelihood test for overall survival (OS) and recurrence-free survival (RFS). A Lasso Cox regression model was further developed using Glmnet by optimizing lambda at minimum mean cross-validated error. Pts were randomly and evenly split into training and testing datasets. Results: Initial univariate Cox PH regression model screening identified 6 cellular and 2 serum protein biomarkers associated with OS and RFS. Enriched populations of CTLA4 + Treg (CD3 + /CD4 + /CD25 hi+ /CD152 + ) and monocytic (M)-MDSC (Lin-CD33 + /HLA-DR lo+ /CD14 + /CD15 + ) were identified as being associated with poor outcome, while enriched populations of CXCR3 + /CD4 + T cells, CXCR3 + /CD8 + T cells, CTLA4 + /INFg + /CD8 + T cells and CD39 + Treg (CD3 + /CD4 + /CD25 hi+ /CD39 + ) were associated with better outcome. Higher levels of CCL3 and CXCL11 chemokines in serum were associated with improved OS and RFS. To develop a prognostic model predictive of ipi treatment benefits, we focused on top ranked biomarkers and generated and tested a Lasso Cox regression model based on CTLA4 + Treg, M-MDSC and CXCR3 + /CD8 + T cell populations using a training subset (N = 105 ipi pts). This model was predictive of pt OS and RFS in the testing subset (N = 105) with C-index = 0.67. To examine broader applicability of our Lasso Cox model, we analyzed an additional 119 pts treated on the IFN control arm. By incorporating treatment arm as an interaction term with our 3 biomarker Lasso Cox score, our model was determined to be predictive of risk in pts treated with ipi but not IFN. Conclusions: Our analysis confirms the predictive value of a 3 biomarker Lasso Cox score predicated on CTLA4 + Treg, M-MDSC and CXCR3 + /CD8 + T cell content in patient blood at baseline as it relates to adjuvant ipi treatment outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e21557
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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