Author
Daniel Waterkamp
Other affiliations: Hoffmann-La Roche
Bio: Daniel Waterkamp is an academic researcher from Genentech. The author has contributed to research in topics: Atezolizumab & Docetaxel. The author has an hindex of 22, co-authored 43 publications receiving 6691 citations. Previous affiliations of Daniel Waterkamp include Hoffmann-La Roche.
Topics: Atezolizumab, Docetaxel, Bevacizumab, Colorectal cancer, Carboplatin
Papers
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Aix-Marseille University1, Genentech2, Samsung Medical Center3, Seconda Università degli Studi di Napoli4, Wayne State University5, Pontifícia Universidade Católica do Rio Grande do Sul6, University of California, Los Angeles7, European Institute of Oncology8, Istanbul University9, Seoul National University Bundang Hospital10, University of California, Davis11
TL;DR: Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression populations, and overall survival improvement was similar in patients with squamous non-squamous lung cancer.
3,496 citations
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TL;DR: This open-label, phase 2 randomised controlled trial assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumours and tumour-infiltrating immune cells and in the intention-to-treat population.
2,185 citations
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TL;DR: The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer.
Abstract: Summary Background Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer. Methods For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m 2 orally twice a day on days 1–14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939. Findings From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70–87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3–11·4] vs 5·1 months [4·2–6·3]; hazard ratio 0·53 [0·41–0·69]; p vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]). Interpretation The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. Funding F Hoffmann-La Roche.
532 citations
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TL;DR: Data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration, and trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment.
Abstract: Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8(+) T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8(+) T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration.
515 citations
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TL;DR: Bvacizumab-FOLFOXIRI was associated with higher response and resection rates and prolonged PFS versus bevac Zimab-mFOL FOX-6 in patients with initially unresectable liver metastases from colorectal cancer.
256 citations
Cited by
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Yale University1, Netherlands Cancer Institute2, Seoul National University Hospital3, Hebron University4, University of Navarra5, Mayo Clinic6, Samsung Medical Center7, Rush University Medical Center8, University of São Paulo9, Pontifical Catholic University of Chile10, Merck & Co.11, University of California, Los Angeles12
TL;DR: In this article, the authors evaluated the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.
4,693 citations
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University of Las Palmas de Gran Canaria1, Sunnybrook Health Sciences Centre2, Autonomous University of Barcelona3, Sanford Health4, Tel Aviv University5, University of Turin6, University of California, Los Angeles7, Kansai Medical University8, Epworth Hospital9, University of Sydney10, University of South Florida11, Merck & Co.12
TL;DR: In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum‐based drug resulted in significantly longer overall survival and progression‐free survival than chemotherapy alone.
Abstract: Background First-line therapy for advanced non–small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. Methods In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy...
4,102 citations
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Aix-Marseille University1, Genentech2, Samsung Medical Center3, Seconda Università degli Studi di Napoli4, Wayne State University5, Pontifícia Universidade Católica do Rio Grande do Sul6, University of California, Los Angeles7, European Institute of Oncology8, Istanbul University9, Seoul National University Bundang Hospital10, University of California, Davis11
TL;DR: Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression populations, and overall survival improvement was similar in patients with squamous non-squamous lung cancer.
3,496 citations
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TL;DR: Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy, suggesting that a broader view of cancer immunity is required.
Abstract: Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy. In the context of the cancer-immunity cycle, such factors combine to represent the inherent immunological status - or 'cancer-immune set point' - of an individual.
3,145 citations