Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial

Robert, Caroline; Ribas, Antoni; Wolchok, Jedd D.; Hodi, F. Stephen; Hamid, Omid; Kefford, Richard; Weber, Jeffrey S.; Joshua, Anthony M.; Hwu, Wen Jen; Gangadhar, Tara C.; Patnaik, Amita; Dronca, Roxana S.; Zarour, Hassane M.; Joseph, Richard W.; Boasberg, Peter D.; Chmielowski, Bartosz; Mateus, Christine; Postow, Michael A.; Gergich, Kevin; Elassaiss-Schaap, Jeroen; Li, Xiaoyun Nicole; Iannone, Robert; Ebbinghaus, Scot; Kang, Soonmo Peter; Daud, Adil

doi:10.1016/s0140-6736(14)60958-2

Cited by 1,600 publications

(1,209 citation statements)

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“…48,166 In this setting, it is tempting to hypothesize that the clinical profile of anticancer chemotherapy based on ICD inducers may be considerably ameliorated by the concomitant administration of various immunostimulatory interventions, 167 in particular checkpoint blockers such as the cytotoxic T lymphocyte-associated protein 4 (CTLA4)-targeting mAb ipilimumab and the programmed cell death 1 (PDCD1)-targeting mAbs pembrolizumab and nivolumab. [168][169][170][171] The results of several trials that have already been launched will clarify the actual clinical value of such combinatorial immunochemotherapeutic paradigms.…”

Section: Resultsmentioning

confidence: 99%

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

et al. 2015

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Section: Resultsmentioning

confidence: 99%

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

et al. 2015

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“…Studies have demonstrated that after initial apparent disease progression, some patients derive clinical benefit from continued administration of immunotherapy [22,38,57,111,[118][119][120][121]. In a phase 3 study (CheckMate 025), 69% of patients with metastatic RCC treated with nivolumab beyond first progression subsequently demonstrated tumor reduction in target lesions, and almost half (48%) had a 30% reduction in tumor burden from baseline [111].…”

Section: Pseudoprogression With Icbsmentioning

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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“…Ultimately, accelerated approval was granted based on a Phase I clinical trial showing efficacy in 173 patients with ipilimumab-refractory melanoma. 83 Patients were treated at either the 2-mg/ kg dose or at the higher 10-mg/kg dose level. At both dose levels, 24% of patients exhibited a radiographic response to therapy, and this effect lasted 1.4 to 8.5 months and continued beyond this point in most patients.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…The most commonly reported adverse events included fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. 83 Importantly, PD-1 blockade was effective in patients who had previously progressed with ipilimumab therapy, reflecting the complementary effects of the various checkpoint inhibitors.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

Eskander

Tewari

2015

Clinical Therapeutics

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Purpose: In 2014, the US Food and Drug Administration approved the first targeted agent, bevacizumab, in the treatment of advanced stage, persistent, or recurrent cervical cancer. This oncologic milestone has catalyzed interest in the investigation of alternate therapies, including immunotherapy, in an effort to extend life and possibly cure patients with advanced stage disease.Methods: This review article focuses on the evolving paradigm of immunotherapy in the treatment of cervical cancer, describing the biologic basis of this treatment modality and discussing applicable Phase I to II clinical trials.Findings: To date several trials have been conducted exploring vaccine-based therapies, adoptive T-cell therapy, and immune-modulating agents in patients with cervical cancer with promising results.Implications: Immunotherapy represents a promising therapeutic paradigm in the treatment of advanced cervical cancer. Additional investigation is warranted to try and identify alternate immune targets and predictors of response, allowing for the selection of patients most likely to benefit from immune-based treatments. (Clin Ther. 2015;37:20-38) & 2015 Elsevier HS Journals, Inc. All rights reserved.

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Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial

Cited by 1,600 publications

References 29 publications

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

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