Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial

Ribas, Antoni; Puzanov, Igor; Dummer, Reinhard; Schadendorf, Dirk; Hamid, Omid; Robert, Caroline; Hodi, F. Stephen; Schachter, Jacob; Pavlick, Anna C.; Lewis, Karl D.; Cranmer, Lee D.; Blank, Christian U.; O’Day, Steven; Ascierto, Paolo A.; Salama, April K.S.; Margolin, Kim; Loquai, Carmen; Eigentler, Thomas; Gangadhar, Tara C.; Carlino, Matteo S.; Agarwala, Sanjiv S.; Moschos, Stergios J.; Sosman, Jeffrey A.; Goldinger, Simone M.; Shapira‐Frommer, Ronnie; González, René; Kirkwood, John M.; Wolchok, Jedd D.; Eggermont, Alexander; Li, Xiaoyun Nicole; Zhou, Wei; Zernhelt, Adriane M; Lis, Joy; Ebbinghaus, Scot; Kang, S. Peter; Daud, Adil

doi:10.1016/s1470-2045(15)00083-2

Cited by 1,429 publications

(1,073 citation statements)

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“…The spectrum of toxicities with these agents was similar to that observed for ipilimumab, although the frequency and severity of adverse events was lower (approximately 10-15% for grade 3-4 adverse events) 80,85,86 . Subsequent clinical trials demonstrated the efficacy of both anti-PD-1 agents in terms of ORR and PFS in the second-line setting after ipilimumab treatment 87,88 , and in terms of overall survival with frontline nivolumab 89 , compared with chemotherapy in each case.…”

Section: Immunotherapy With Immune-checkpoint Inhibitorsmentioning

confidence: 99%

Targeted agents and immunotherapies: optimizing outcomes in melanoma

et al. 2017

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Section: Immunotherapy With Immune-checkpoint Inhibitorsmentioning

confidence: 99%

Targeted agents and immunotherapies: optimizing outcomes in melanoma

et al. 2017

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“…However, as novel agents extend patient survival times, it becomes increasingly difficult to conduct long clinical trials in order to measure OS [75,76]. Although the use of ICBs has improved survival in melanoma over standard chemotherapy, with some patients experiencing OS of 3 to 5 years [77,78], when the follow-up is less than 1 year, median OS is usually not reached [22,23,39,43]. Therefore, there is an interest in validating surrogate endpoints that can accurately predict survival benefit in clinical trials of immunotherapy and using these surrogate endpoints for drug approval [75].…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

“…Generally, ICBs have been shown to significantly improve ORR when compared with standard therapies, for example in patients with melanoma [22,23,39], RCC [28], and NSCLC with high PD-L1 expression [43] (Table 2). ICBs have also been shown to prolong duration of response (DOR) when compared with standard therapies (Table 2) [22,23,25,39,42,43,46].…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

“…ICBs have also been shown to prolong duration of response (DOR) when compared with standard therapies (Table 2) [22,23,25,39,42,43,46]. The use of alternative endpoints as a surrogate for OS is an area of ongoing research, and further knowledge on this topic is likely to emerge in the near future.…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

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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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“…The six-month progression-free rate, the primary endpoint of the study, was 34, 38, and 16%, respectively (pembrolizumab 2 mg/kg versus chemotherapy; HR 0.57; 95CI 0.45-0.73; p<0.0001; and pembrolizumab 10 mg/kg versus chemotherapy HR 0.50, 95CI 0.39-0.64; p<0.0001), with objective responses occurring in 21-26% of the cases. 36 Similarly, in the phase 3 CheckMate 037 study, 405 previously treated patients received either nivolumab or investigator's choice of chemotherapy. Objective responses were reported in 31.7% in the nivolumab group vs. 10.6% in the chemotherapy group, and less toxic effects were seen with nivolumab (rate of grade 3-4 adverse events: 9% vs. 32%).…”

Section: Introductionmentioning

confidence: 99%

Treatment of advanced melanoma - A changing landscape

Hepner

Salgues

Anjos

et al. 2017

Rev. Assoc. Med. Bras.

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Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.

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Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial

Abstract: Merck Sharp & Dohme.

Cited by 1,429 publications

References 32 publications

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Treatment of advanced melanoma - A changing landscape

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