Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial

Weber, Jeffrey S.; D’Angelo, Sandra P.; Minor, David R.; Hodi, F. Stephen; Gutzmer, Ralf; Neyns, Bart; Höeller, Christoph; Khushalani, Nikhil I.; Miller, Wilson H.; Lao, Christopher D.; Linette, Gerald P.; Thomas, Luc; Lorigan, Paul; Grossmann, Kenneth F.; Hassel, Jessica C.; Maio, Michele; Sznol, Mario; Ascierto, Paolo A.; Mohr, Peter; Chmielowski, Bartosz; Bryce, Alan H.; Svane, Inge Marie; Grob, Jean-Jacques; Krackhardt, Angela M.; Horak, Christine E.; Lambert, Alexandre; Yang, Allison L.; Larkin, James

doi:10.1016/s1470-2045(15)70076-8

Cited by 2,333 publications

(1,798 citation statements)

References 25 publications

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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%

“…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%

“…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]. In another phase 3 study (CheckMate 037) investigating nivolumab in patients with advanced melanoma, 31% received treatment beyond progression, and 27% of these had a greater than 30% reduction in target lesions [22]. Similar findings were observed in 62 patients with recurrent or metastatic HNSCC treated with nivolumab beyond progression in the phase 3 CheckMate 141, with 24% of these patients experiencing tumor reduction [118], and in 137 patients with advanced or metastatic UC treated with atezolizumab beyond progression in the phase 2 IMvigor 210, with 33% experiencing tumor reduction [120].…”

Section: Pseudoprogression 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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Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Section: Pseudoprogression With Icbsmentioning

confidence: 99%

Section: Pseudoprogression With Icbsmentioning

confidence: 99%

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Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Association of Anti–Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma

et al. 2020

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IMPORTANCESince 2011, many patients with metastatic melanoma have been treated with ipilimumab therapy and have developed severe immune-related adverse events (AEs). Because several immune therapies are now available to treat metastatic melanoma, a better knowledge of mechanisms and recurrence risks of immune-related AEs is needed before reintroduction of immunotherapies.OBJECTIVES To evaluate the risk of a recurrence of immune toxic effects associated with anti-programmed cell death 1 antibody (anti-PD-1) therapy after discontinuation of ipilimumab monotherapy because of severe AEs. DESIGN, SETTINGS, AND PARTICIPANTSThis cohort study conducted at 19 French melanoma referral centers included patients with metastatic melanoma who experienced severe immune-related AEs after ipilimumab therapy and then were treated with anti-PD-1 therapy

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A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors

2018

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Key Points Question Does the treatment effect size differ between overall survival and progression-free survival for PD-1 (programmed cell death 1) inhibitors used in patients with advanced solid tumors, and are overall survival and progression-free survival correlated? Findings This meta-analysis of 12 randomized clinical trials found no significant correlation between overall survival and progression-free survival in terms of medians and gains in medians, but their hazard ratios were significantly correlated. The protective effects of treatment were greater for overall survival than for progression-free survival. Meaning Progression-free survival cannot adequately capture the benefit of PD-1 inhibitors; thus, overall survival should remain the gold standard end point for trials of PD-1 inhibitors.

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Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial

Cited by 2,333 publications

References 25 publications

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Association of Anti–Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma

A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors

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