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Safety and efficacy of nivolumab in challenging subgroups with advanced melanoma who progressed on or after ipilimumab treatment: A single-arm, open-label, phase II study (CheckMate 172).

Published on Nov 1, 2019in European Journal of Cancer6.68
· DOI :10.1016/J.EJCA.2019.08.014
Dirk Schadendorf95
Estimated H-index: 95
,
Paolo A. Ascierto61
Estimated H-index: 61
+ 25 AuthorsPaul C. Nathan36
Estimated H-index: 36
Abstract
Abstract Background Limited data are available on nivolumab in challenging subgroups with advanced melanoma. We report outcomes of nivolumab after prior ipilimumab in patients who are typically excluded from clinical trials. Patients and methods In this phase II, single-arm, open-label, multicentre study (CheckMate 172), patients with advanced melanoma who progressed on or after ipilimumab received nivolumab 3 mg/kg, every 2 weeks for up to 2 years. The primary objective was incidence of grade ≥3, treatment-related select adverse events (AEs). Results At a minimum follow-up of 18 months, grade ≥3 treatment-related select AEs with the most variation across subgroups were diarrhoea and colitis (1.1% [n = 11] and 0.3% [n = 3] for the total population [n = 1008]; 0.6% [n = 1] and 0.6% [n = 1] for patients with an asymptomatic central nervous system [CNS] metastasis [n = 165; 16.4%]; 4.5% [n = 3] and 3.0% [n = 2] for patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 2 [n = 66; 6.5%]; 2.4% [n = 2] and 0% for those who experienced a grade 3/4 immune-related AE [irAE] with prior ipilimumab [n = 84; 8.3%]; and 0% and 0% for autoimmune disease [n = 25; 2.5%], respectively). Median overall survival was 21.4 months in the total population and was 11.6, 2.4, 21.5, and 18.6 months in patients with a CNS metastasis, ECOG PS 2, a grade 3/4 irAE with prior ipilimumab, and autoimmune disease, respectively. Conclusions In this large, phase II clinical trial of patients with advanced melanoma who progressed on or after ipilimumab, nivolumab demonstrated a safety profile consistent with that of prior clinical trials. ClinicalTrials.gov ID: NCT02156804 .
  • References (21)
  • Citations (6)
References21
Newest
#1Paul C. NathanH-Index: 36
#2Paolo A. AsciertoH-Index: 61
Last. Dirk SchadendorfH-Index: 95
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Abstract Background Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, ever...
9 CitationsSource
#1Paolo A. AsciertoH-Index: 61
#2Georgina V. Long (USYD: University of Sydney)H-Index: 73
Last. Victoria Atkinson (Greenslopes Private Hospital)H-Index: 19
view all 28 authors...
Importance This analysis provides long-term follow-up in patients withBRAFwild-type advanced melanoma receiving first-line therapy based on anti–programmed cell death 1 receptor inhibitors. Objective To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreatedBRAFwild-type advanced melanoma. Design, Setting, and Participants This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-bl...
19 CitationsSource
#1Georgina V. Long (USYD: University of Sydney)H-Index: 73
#2Victoria Atkinson (UQ: University of Queensland)H-Index: 19
Last. Grant A. McArthur (University of Melbourne)H-Index: 73
view all 12 authors...
Summary Background Nivolumab monotherapy and combination nivolumab plus ipilimumab increase proportions of patients achieving a response and survival versus ipilimumab in patients with metastatic melanoma; however, efficacy in active brain metastases is unknown. We aimed to establish the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with active melanoma brain metastases. Methods This multicentre open-label randomised phase 2 trial was done at four sites in ...
104 CitationsSource
#1Douglas B. JohnsonH-Index: 40
Last. Daniel Y. WangH-Index: 8
view all 3 authors...
In this article, we detail the experience with immune checkpoint inhibitors in patients with autoimmune disease.
3 Citations
#1Annie Wong (University of Melbourne)H-Index: 5
#2Molly Williams (Peter MacCallum Cancer Centre)H-Index: 1
Last. Grant A. McArthur (University of Melbourne)H-Index: 73
view all 8 authors...
Background Antiprogrammed death-1 antibodies (anti-PD1) have response rates of 40% in metastatic melanoma. Patients with poor performance status (PS) were excluded from clinical trials, yet use of anti-PD1 is widespread in clinical practice. Literature regarding clinical and palliative care outcomes in patients with poor PS treated with anti-PD1 is lacking. Methods Retrospective review of outcomes for all patients with advanced melanoma treated with anti-PD1 between 2012 and June 2015 at Peter M...
6 CitationsSource
#1Daniel N. CagneyH-Index: 10
#2Allison MartinH-Index: 8
Last. Ayal A. AizerH-Index: 27
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Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program. Methods: We identified 1302166 patients with diagnoses of nonhematol...
40 CitationsSource
#1James LarkinH-Index: 62
#2David R. Minor (CPMC: California Pacific Medical Center)H-Index: 23
Last. Jeffrey S. Weber (NYU: New York University)H-Index: 18
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PurposeUntil recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma.Patients and MethodsPatients were stratified by programmed death-...
89 CitationsSource
#1Douglas B. Johnson (VUMC: Vanderbilt University Medical Center)H-Index: 40
#2Ryan J. Sullivan (Harvard University)H-Index: 42
Last. Alexander M. Menzies (USYD: University of Sydney)H-Index: 36
view all 3 authors...
Immune checkpoint inhibitors, including those targeting the programmed cell death 1/programmed cell death ligand 1 and cytotoxic T lymphocyte antigen 4 pathways, are revolutionizing cancer therapeutics. Both activity and toxicities largely stem from unleashing tumor- or host-specific cytotoxic T cells. Many patients seen in routine clinical practice have not qualified for or have been seriously underrepresented in immune checkpoint inhibitor clinical trials. Thus, a major gap in knowledge regard...
50 CitationsSource
#1Dirk SchadendorfH-Index: 95
#2Paolo A. AsciertoH-Index: 61
Last. Paul C. NathanH-Index: 36
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9524Background: In the phase III CheckMate 037 study, NIVO improved the objective response rate and progression-free survival with less toxicity vs chemotherapy in patients (pts) with MEL who progr...
8 CitationsSource
#1Jason J. LukeH-Index: 27
#2Keith T. FlahertyH-Index: 93
Last. Georgina V. LongH-Index: 73
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In less than a decade, the treatment landscape of metastatic melanoma has changed dramatically. Novel targeted agents and immunotherapies are revolutionizing patient outcomes, but the range of available drugs complicates clinical decision-making. Herein, the authors chart the therapeutic advances and review the current evidence that can be used to guide therapeutic decisions for individual patients with metastatic melanoma, highlighting knowledge gaps.
223 CitationsSource
Cited By6
Newest
#1Lorenzo Salvati (UniFI: University of Florence)H-Index: 1
#2Mario MandalàH-Index: 44
Last. Daniela Massi (UniFI: University of Florence)H-Index: 45
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#1Yingying Hu (HMU: Harbin Medical University)H-Index: 7
#2Jian Gong (SPU: Shenyang Pharmaceutical University)
Last. Xin Hai (HMU: Harbin Medical University)H-Index: 1
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Abstract Background Although colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs. Methods Based on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ...
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#1Anna Czarnecka (PAN: Polish Academy of Sciences)H-Index: 7
#1Anna M. Czarnecka (PAN: Polish Academy of Sciences)H-Index: 20
Last. Piotr RutkowskiH-Index: 50
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Introduction: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients' safety and therapy continuation.Areas covered: Long term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with au...
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#1Gennaro RiccioH-Index: 1
#1Gennaro Riccio (Stazione Zoologica Anton Dohrn)H-Index: 8
Last. Chiara LauritanoH-Index: 16
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Microalgae are photosynthetic microorganisms adapted to live in very different environments and showing an enormous biochemical and genetic diversity, thus representing an excellent source of new natural products with possible applications in several biotechnological sectors. Microalgae-derived compounds have shown several properties, such as anticancer, antimicrobial, anti-inflammatory, and immunomodulatory. In the last decade, compounds stimulating the immune system, both innate immune respons...
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#1A. PrelajH-Index: 4
#2Roberto FerraraH-Index: 11
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Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group...
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#1Paul C. NathanH-Index: 36
#2Paolo A. AsciertoH-Index: 61
Last. Dirk SchadendorfH-Index: 95
view all 28 authors...
Abstract Background Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, ever...
9 CitationsSource