Author
Ann Christine Thastrom
Bio: Ann Christine Thastrom is an academic researcher from Genentech. The author has contributed to research in topics: Atezolizumab & Carboplatin. The author has an hindex of 5, co-authored 5 publications receiving 1383 citations.
Papers
More filters
New York University1, Icahn School of Medicine at Mount Sinai2, Memorial Sloan Kettering Cancer Center3, Queen Mary University of London4, Yale University5, Harvard University6, Université Paris-Saclay7, University of Milan8, University of Navarra9, MedStar Georgetown University Hospital10, Netherlands Cancer Institute11, University of Virginia12, Stanford University13, Technische Universität München14, Mayo Clinic15, University of California, Los Angeles16, Wayne State University17, Princess Margaret Cancer Centre18, University of Southern California19, Cleveland Clinic20, Fred Hutchinson Cancer Research Center21, Genentech22
TL;DR: Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer.
1,578 citations
Icahn School of Medicine at Mount Sinai1, Hospital General Universitario Gregorio Marañón2, National and Kapodistrian University of Athens3, Monash University4, Charité5, Keio University6, University of Barcelona7, Kanazawa University8, Istanbul Medeniyet University9, Istanbul University10, Samsung Medical Center11, Hungkuang University12, Fudan University13, Hoffmann-La Roche14, Genentech15, University of Texas MD Anderson Cancer Center16
TL;DR: The results of IMvigor130 support the use of atezolizumab plus platinum-based chemotherapy as a potential first-line treatment option for metastatic urothelial carcinoma and the safety profile of the combination was consistent with that observed with the individual agents.
470 citations
New York University1, Icahn School of Medicine at Mount Sinai2, Institut Gustave Roussy3, Stanford University4, Mayo Clinic5, Princess Margaret Cancer Centre6, University of Southern California7, Services Hospital8, Memorial Sloan Kettering Cancer Center9, Royal Free London NHS Foundation Trust10, Thomas Jefferson University11, Genentech12
TL;DR: Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts, and the primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1.
Abstract: LBA4500Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR > 30 but < 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71%...
26 citations
TL;DR: Platinum-based chemo is the standard of care for most pts with untreated mUC, although clinical outcomes remain poor, and Atezo (anti–PD-L1) was approved in the United States, Europe, and elsewhere.
Abstract: TPS4589Background: Platinum-based chemo is the standard of care for most pts with untreated mUC, although clinical outcomes remain poor Atezo (anti–PD-L1) was approved in the United States, Europe
25 citations
TL;DR: This analysis was performed to assess the impact of prior therapy on atezo outcomes in mUC and found that Objective responses, including CRs, occurred regardle...
Abstract: 323Background: Atezo is approved in the US for mUC and non-small cell lung cancer after prior treatment with chemotherapy. > 40% of mUC pts in the Phase 2 IMvigor210 study received ≥ 2prior metastatic regimens (Rosenberg, Lancet 2016). This analysis was performed to assess the impact of prior therapy on atezo outcomes in mUC. Methods: mUC pts in the platinum-pretreated IMvigor210 cohort (NCT02108652) received atezo 1200 mg IV q3w until loss of clinical benefit. Study endpoints analyzed by the number of prior treatment regimens included RECIST v1.1 ORR (central review), complete response (CR) rate, median durations of response (mDOR) and survival (mOS) and adverse event rate. Results: Evaluable pts (N = 310) had a median age of 66 years, and 78% had visceral mets (31% liver). 82% of pts had prior systemic treatment for mUC; number of prior regimens ranged from 1 to ≥ 4 (Table). 73% of pts received prior cisplatin, and 26% had carboplatin (no cisplatin). Objective responses, including CRs, occurred regardle...
6 citations
Cited by
More filters
TL;DR: Tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent were examined and major determinants of clinical outcome were identified and suggested that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.
Abstract: Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.
2,808 citations
TL;DR: The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer.
Abstract: Side Effects of Immune Checkpoint Blockade The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer. This review surveys the adverse effects and their management.
2,658 citations
University of Alabama at Birmingham1, University of South Florida2, Vanderbilt University3, City of Hope National Medical Center4, Fox Chase Cancer Center5, University Of Tennessee System6, Brigham and Women's Hospital7, Seattle Cancer Care Alliance8, Case Western Reserve University9, Roswell Park Cancer Institute10, Northwestern University11, Harvard University12, University of Nebraska Medical Center13, University of Utah14, Memorial Sloan Kettering Cancer Center15
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
1,545 citations
TL;DR: TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required.
1,490 citations
TL;DR: The roles of the PD-1-PD-L1 axis in cancer is reviewed, focusing on recent findings on the mechanisms that regulate PD-L 1 expression at the transcriptional, posttranscriptional, and protein level, to inform the design of more precise and effective cancer immune checkpoint therapies.
1,211 citations