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Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 platform trial

ABSTRACT: Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 platform trial

PROVIDER: PRJNA727320 | ENA |

REPOSITORIES: ENA

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Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 platform trial

Project description:Durvalumab with olaparib was one of the experimental regimens evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2- and HR+HER2- signatures. We hypothesized that (pre-treatment) expression-based immune signatures may predict response to the immune checkpoint inhibitor durvalumab and signatures related to DNA repair deficiency (DRD) may associate with response to olaparib. In this analysis, we assessed 13 expression based signatures related to immune, DRD, proliferation and estrogen signaling as specific predictor of pathologic complete response (pCR) to durvalumab/olaparib.

2021-06-10 | GSE173839 | GEO

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2-positive breast cancer in the adaptively randomized I-SPY2 trial.

Project description:Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2-positive breast cancer in the adaptively randomized I-SPY2 trial.

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Olaparib

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Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2-positive breast cancer in the adaptively randomized I-SPY2 trial.

Project description:Ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel plus trastuzumab and pertuzumab (THP) are two of the experimental regiments evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer. In pre-defined analyses we assessed 10 biomarkers at the pre-treatment timepoint in the HER2, ER/PR, and proliferation pathways to test their association with pCR (complete pathologic response).

2021-08-24 | GSE181574 | GEO

I-SPY2-990 mRNA/RPPA Data Resource: RPPA component

Project description:The RPPA component of the I-SPY2-990 mRNA/RPPA Data Resource contains protein/phosphoprotein data from pre-treatment laser capture microdissected (LCM) tumor biopsies for 139 key signaling proteins/phosphoproteins in cancer for 736 patients from 8 arms of the neoadjuvant I-SPY2 TRIAL (NCT01042379) for aggressive early stage breast cancer [194 Control (Ctr); 63 veliparib/carboplatin (VC); 105 neratinib (N); 87 MK2206; 128 trebananib; 49 TDM1/pertuzumab(P); 43 H/P; and 67 pembrolizumab (pembro)]. This record also contains clinical data for these patients, including HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. RPPA endpoints assayed are from hormone receptor (n=4), HER family (n=14), cell cycle/proliferation (n=20), immune (n=18), DNA repair deficiency (DDR; n=15), AKT/mTOR/PI3K (n=7), apoptosis/autophagy (n=10), IGF1R (n=6), TIE/ANG (n=4), growth/survival/metabolism (n=22) and RTK (n=19) pathways. For gene expresson data for all 736 patients with RPPA data, plus an additional 150 patients for a total 987 patients from 10 arms of I-SPY2 (mRNA component of the I-SPY2-990 Data Resource), see the companion GEO record/subseries GSE194040.

2022-05-25 | GSE196093 | GEO

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2<sup>+</sup> breast cancer in the adaptively randomized I-SPY2 trial.

Project description:HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.

| S-EPMC8571284 | biostudies-literature

Genome-wide analysis of enzalutamide- and/or olaparib-responsive gene expression in prostate cancer cells

Project description:Analysis of enzalutamide- and/or olaparib-responsive gene expression in prostate cancer cells. The hypothesis tested in the present study was that enzalutamide influences the expression of genes that are involved in important bioprocesses in prostate cance rcells, including DNA damage response genes and this effect may synergize with poly(ADP-ribose) polymerase inhibitor olaparib in cytotoxicity to prstate cancer cells. prostate cancer cells were pretreated with enzalutamide or vehicle control DMSO for 24 h, followed by treatment with enzalutamide, olaparib, enzalutamide+olaparib, or vehicle control DMSO for 48 h. Gene expression in enzalutamide+olaparib-treated cells was compared with taht in vehicle control- and single agent-treated cells.

2016-07-03 | E-GEOD-69249 | biostudies-arrayexpress

I-SPY2-990 mRNA/RPPA Data Resource: mRNA component

Project description:The I-SPY2-990 mRNA/RPPA Data Resource contains gene expression and clinical data for 987 patients from 10 arms of the neoadjuvant I-SPY2 TRIAL for aggressive early stage breast cancer [210 Control (Ctr); 71 veliparib/carboplatin (VC); 114 neratinib (N); 93 MK2206; 106 ganitumab; 93 ganetespib; 134 trebananib; 52 TDM1/pertuzumab(P); 44 H/P; 69 pembrolizumab (pembro)]. All 987 patients have pretreatment full transcriptome expression data on over ~19,000 genes assayed on Agilent 44K. Clinical data includes HR, HER2 and MP status, response (pCR or no pCR), and treatment arm. The ISPY2-990 mRNA/RPPA Data Resource also includes normalized pre-treatment LCM-RPPA data for 139 key signaling proteins/phosphoproteins in cancer for 736 patients (see companion GEO record GSE196093 for data and details).

2022-05-25 | GSE194040 | GEO

Activation of Wnt signaling promotes olaparib resistant ovarian cancer.

Project description:Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10 and C18) and parental PEO1 (P1 and P2) cells was performed in order to determine mechanisms of acquired resistance in the resistant cell lines. PEO1 parental cell lines were authenticated prior to sequencing. PEO1 parental were confirmed to be BRCA2-mutated (5139C>G). Olaparib PEO1 resistant cells were generated through a step-wise escalation of olaparib (10nM to 8uM olaparib). In olaparib resistant lines an increase canonical Wnt signaling and loss of of non-canonical Wnt signaling was observed.

2018-07-28 | GSE117765 | GEO

Transcriptome profiling of Olaparib-resistant (OlapR) prostate cancer cell lines

Project description:Acquisition of resistance to the PARP inhibitor, Olaparib, constitutes a major challenge for the treatment of advanced prostate cancer. The purpose of this study was to identify molecular targets responsible for the development of acquired Olaparib resistance in advanced prostate cancer. Towards this goal, next-generation sequencing (NGS)-based gene expression profiling (RNA-Sequencing; RNA-Seq) was performed on castration-sensitive prostate cancer (CSPC)/Olaparib-sensitive LNCaP cells, castration-sensitive prostate cancer (CSPC)/Olaparib-resistant LN-OlapR cells, castration-resistant prostate cancer (CSPC)/Olaparib-sensitive C4-2B cells, and castration-resistant prostate cancer (CSPC)/Olaparib-resistant 2B-OlapR cells.

2023-12-06 | GSE249514 | GEO

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