Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial

Fehrenbacher, Louis; Spira, Alexander I.; Ballinger, Marcus; Kowanetz, Marcin; Vansteenkiste, Johan; Mazières, Julien; Park, Keunchil; Smith, David C.; Artal, Ángel; Lewanski, Conrad; Braiteh, Fadi; Waterkamp, Daniel; He, Pei; Zou, Wei; Chen, Daniel S.; Yi, Jing; Sandler, Alan; Rittmeyer, Achim

doi:10.1016/s0140-6736(16)00587-0

Cited by 2,354 publications

(2,223 citation statements)

References 26 publications

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“…In addition to clinical trials testing anti‐PD‐1 antibody treatment, antibodies to the PD‐1 ligand, PD‐L1 have also been tested. In a trial with non‐small‐cell lung cancer, treatment with the anti‐PD‐L1 antibody atezolizumab prolonged patient survival compared to patients that were treated with docetaxel 30. This was particularly the case for patients with elevated expression of PD‐L1.…”

Section: Introductionmentioning

confidence: 99%

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Levingston

Young

2017

Intl Journal of Cancer

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A carcinogen‐induced premalignant oral lesion model that progresses to oral cancer was used to examine the impact of blocking PD‐1 on cytokine expression and on progression of lesions to cancer. The results of this study show increased production of IL‐2 and the inflammatory cytokines IL‐6, IL‐17 and TNF‐α by spleen cells of lesion‐bearing mice that were treated with PD‐1 antibody for 1 week compared to cytokine production by spleen cells of lesion‐bearing mice treated with control antibody. Production of IFN‐γ increased at 3 weeks of PD‐1 antibody treatment, although production of the other Th1 and inflammatory mediators declined. By 5 weeks, levels of these cytokines declined for both control and PD‐1 antibody‐treated mice. Flow cytometric analysis for IFN‐γ‐expressing cells showed shifts in CD4+ cells expressing IFN‐γ consistent with the changes in cytokine secretion. Whether or not treatment generated reactivity to lesions or HNSCC was determined. Spleen cells from PD‐1 antibody‐treated mice were stimulated by lysates of premalignant lesion and HNSCC tongue tissues to produce increased levels of Th1 and select inflammatory cytokines early in the course of PD‐1 antibody treatment. However, with continued treatment, reactivity to lesion and HNSCC lysates declined. Analysis of clinical response to treatment suggested an early delay in lesion progression but, with continued treatment, lesions in PD‐1 antibody‐treated mice progressed to the same degree as in control antibody‐treated mice. Overall, these results show an early beneficial response to PD‐1 antibody treatment, which then fails with continued treatment and lesion progression.

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Section: Introductionmentioning

confidence: 99%

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Levingston

Young

2017

Intl Journal of Cancer

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“…In addition, IO therapies may lead to more long‐term efficacy, as exemplified by more substantial OS separation at late times. The applicability of such a modeling framework for IO therapies was evaluated based on data from the POPLAR study comparing atezolizumab vs. docetaxel in patients with advanced pretreated NSCLC 33, 36. In the POPLAR study, TGI profiles in the atezolizumab and docetaxel arm crossed at about 25 weeks, with more initial shrinkage in docetaxel‐treated patients, and slower on‐treatment KG in atezolizumab‐treated patients.…”

Section: Opportunities For Modeling and Simulationmentioning

confidence: 99%

Challenges and Opportunities in Dose Finding in Oncology and Immuno‐oncology

Jin

Hyman

et al. 2018

Clinical Translational Sci

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“…In fact, tumor mutational burden, known to enhance neoantigen formation, has been shown to be associated with increased response to ICBs, and in some cases improved OS as well, across tumor types such as melanoma [99,100], NSCLC [101], and UC [54,56,102]. Baseline gene expression profiling has also been correlated with response to ICBs; specifically, interferon gamma (IFNγ) signature, which is indicative of an inflammatory tumor microenvironment, is associated with responsiveness to ICBs in several tumor types, including melanoma [103], UC [32,54,104,105], NSCLC [58,106], HNSCC [103], and gastric cancer [103].…”

Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial

Cited by 2,354 publications

References 26 publications

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

Challenges and Opportunities in Dose Finding in Oncology and Immuno‐oncology

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

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