Pseudoprogression in cancer immunotherapy: Rates, time course and patient outcomes.

Kurra, Vikram; Sullivan, Ryan J.; Gainor, Justin F.; Hodi, F. Stephen; Gandhi, Leena; Sadow, Cheryl A.; Harris, Gordon J.; Flaherty, Keith T.; Lee, Susanna

doi:10.1200/jco.2016.34.15_suppl.6580

Cited by 69 publications

(52 citation statements)

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“…[15,16] However, objective response rates are not significantly different between the two criteria in a large retrospective study. [17] Therefore, response criteria is not completely responsible for the remarkable clinical outcome in our study.…”

Section: Discussionmentioning

confidence: 73%

A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma

Patel

Kim

Bassett

et al. 2017

Cancer Immunol Immunother

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Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab. We performed an open-label single-arm phase II study of ipilimumab plus temozolomide in the frontline setting for patients with metastatic melanoma and LDH <=2x upper limit of normal. Ipilimumab was given at 10 mg/kg on day 1 and temozolomide 200 mg/m2 orally days 1–4 every three weeks for four doses followed by maintenance ipilimumab every 12 weeks plus temozolomide every four weeks. The primary objective of the study was 6-month PFS. A total of 64 patients were enrolled and the 6-month PFS was 45% with median OS of 24·5 months. There were 10 (15·6%) confirmed partial responses and 10 (15·6%) confirmed complete responses. Duration of response amongst responders is 35 months with 10 patients demonstrating an ongoing response at median follow-up of 20 months. There were no deaths or unexpected toxicities on study. The most common gastrointestinal side effects were nausea and constipation rather than diarrhea or colitis. These results suggest that the combination of induction ipilimumab plus temozolomide could potentially be an effective strategy to enhance antitumor activity with a manageable toxicity profile. These findings warrant further evaluation in a large prospective study.

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Section: Discussionmentioning

confidence: 73%

A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma

Patel

Kim

Bassett

et al. 2017

Cancer Immunol Immunother

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“…RECIST 1.1 might not always adequately capture the unique patterns of response that have been well described in clinical trials of these drugs in a low proportion of patients, typically reported as 10% or less, mainly in melanoma studies. 32–34 The true frequency in trials of other malignancies (including non-small-cell lung cancer) is unclear because most trials have reported RECIST 1.1-based response rates, 35 but might be less common based on anecdotal reports. Similarly, whether this pattern is unique to drugs active in the CTLA4–PD-1–PD-L1 pathway is currently unknown.…”

Section: Discussion: Next Steps and Validationmentioning

confidence: 99%

iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics

Seymour

Bogaerts

Perrone

et al. 2017

The Lancet Oncology

1,755

1,401

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Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.

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“…However, it is important to underline that in this study the number of patients with pseudoprogression was small, with only 21 patients according to irRC. Larger analyses are required to confirm this observation (18). , which is characterized by the acceleration of tumor growth during immune checkpoint inhibition.…”

Section: Editorialmentioning

confidence: 98%

Atypical patterns of response to immune checkpoint inhibitors: interpreting pseudoprogression and hyperprogression in decision making for patients’ treatment

Onesti¹,

Freres²,

Jérusalem³

2019

J. Thorac. Dis

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Pseudoprogression in cancer immunotherapy: Rates, time course and patient outcomes.

Cited by 69 publications

References 0 publications

A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma

A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma

iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics

Atypical patterns of response to immune checkpoint inhibitors: interpreting pseudoprogression and hyperprogression in decision making for patients’ treatment

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