Overall survival (OS) and safety results from a phase 3 trial of ipilimumab (IPI) at 3 mg/kg vs 10 mg/kg in patients with metastatic melanoma (MEL)

Ascierto, Paolo A.; Vecchio, Michele Del; Robert, Caroline; Mackiewicz, A.; Chiarion-Sileni, Vanna; Arance, Ana; Schmidt, Henrik; Lebbe, Célèste; Bastholt, Lars; Hamid, Omid; Rutkowski, Piotr; McNeil, Catriona M.; Garbe, Claus; Loquai, Carmen; Dréno, Brigitte; Thomas, Luc; Grob, Jean‐Jacques; Hennicken, Delphine; Qureshi, Anila; Maio, Michele

doi:10.1093/annonc/mdw379.01

Cited by 22 publications

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“…In these studies, however, ipilimumab was used at a different dose: 3 mg/kg in the monotherapy trial versus 10 mg/kg in the combination therapy trial. Ipilimumab monotherapy at 10 mg/kg and 3 mg/kg has been compared directly in the CA184-169 trial 79 , which involved 727 patients; the median overall survival was improved with the higher dose (15.7 months versus 11.5 months; HR 0.84; P <0.04), but at the expense of increased toxicity (rate of grade 3-4 events: 34% versus 19%).The toxicities associated with ipilimumab include immune-related phenomena, such as dermatitis, diarrhoea, colitis and, less commonly, hepatitis, uveitis, and hypophysitis 80 .…”

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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“…As far as melanoma treatment is concerned, grade 3–4 adverse events are in the range of 13% (nivolumab) [2], 34% (ipilimumab 10 mg/kg) [16] and 56.5% for nivolumab in combination with ipilimumab [17]. The rate of patients who permanently discontinued for any grade adverse events ranged from 6% (nivolumab) [2] to 31% (ipilimumab 10 mg/kg) or 38.7% in case of combination nivolumab/ipilimumab [17].…”

Section: Checkpoint Inhibitors In Advanced Melanomamentioning

confidence: 99%

“…Three-year survival rates were 31% versus 23%, respectively. Virtually all subgroups benefited from the 10 mg/kg dose, with the most impressive results seen for BRAF-positive patients (without prior treatment with a BRAF inhibitor), whose HR was 0.65. median PFS, however, was not improved with the higher dose, being 2.8 months in each arm; similarly, the objective response rate (15% vs. 12% for 10 mg/kg vs. 3 mg/kg, respectively) and disease control rate (32% vs. 28%) [16]. …”

Section: Checkpoint Inhibitors In Advanced Melanomamentioning

confidence: 99%

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, November 30th 2016

et al. 2017

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The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies. Monotherapy in pre-treated NSCLC is studied and the use of nivolumab, pembrolizumab and atezolizumab as second-line of advanced NSCLC is demonstrated as well as first line monotherapy and combination therapy in metastatic NSCLC studied. Patients with HNSCC have immunotherapeutic promises as well: the FDA recently approved moAbs targeting immune checkpoint receptors. Nivolumab in combination with ipilumumab showed acceptable safety and encouraging antitumor activity in metastatic renal carcinoma. HCCs have significant amounts of genomic heterogeneity and multiple oncogenic pathways can be activated: the best therapeutic targets identification is ongoing. The treatment of advanced/relapsed EOC remain clearly an unmet need: a better understanding of the relevant immuno-oncologic pathways and their corresponding biomarkers are required. UC is an immunotherapy-responsive disease: after atezolizumab, three other PD-L1/PD-L1 inhibitors (nivolumab, durvalumab, and avelumab) were approved for treatment of platinum-refractory metastatic urothelial carcinoma. Anti-PD-1/PD-L1 monotherapy is associated with a modest response rate in metastatic breast cancer; the addition of chemotherapy is associated with higher response rates. Immunotherapy safety profile is advantageous, although, in contrast to conventional chemotherapy: boosting the immune system leads to a unique constellation of inflammatory toxicities known as immune-related Adverse Events (irAEs) that may warrant the discontinuation of therapy and/or the administration of immunosuppressive agents. Research should explore better combination with less side effects, the right duration of treatments, combination or sequencing treatments with target therapies. At present, treatment decision is based on patient’s characteristics.

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“…Ipilimumab byl v roce 2011 schvá-len v dávce 3 mg/ kg, nicméně v následu-jících letech ještě probíhala studie BMS 169 porovnávající účinnost této nízké dávky proti vysoké dávce 10 mg/ kg. I když výsledky ukazují, že by dávka ipilimumabu 10 mg/ kg proti dávce 3 mg/ kg mohla být účinnější, dochází současně k výraznému zvýšení toxicity, které zá-sadně omezuje jeho využití ve vysokých dávkách [1]. Dalším důvodem je samozřejmě finanční toxicita.…”

Section: Současné Využití Ipilimumabuunclassified

Advances in Immunotherapy of Malignant Melanoma

Krajsová¹

2017

Klin Onkol

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SouhrnRozvoj imunoterapie dramaticky změnil špatnou prognózu metastazujícího maligního melanomu (malignant melanoma -MM). Inhibice kontrolních bodů imunity představuje novou účinnou léčbu. Monoklonální protilátky proti CTLA-4 ipilimumab a proti PD-1 (programme death 1) nivolumab a pembrolizumab prodlužují přežití do progrese i celkové přežití (overal survival -OS) u pa cientů s pokročilým metastazujícím MM. Oba preparáty dosáhly též význam-ného zlepšení doby do relapsu i OS v adjuvantním podávání. Zdá se, že účinnost kombinované imunoterapie ipilimumabem s anti-PD-1 protilátkami převažuje nad monoterapií, ale kombinovaná léčba je provázena vyšší toxicitou. Terapie nežádoucích účinků kombinace ipilimumabu s nivolumabem byla řešena v několika klinických studiích. Zkoumají se nové kombinace jako např. imunoterapie s intralezionální aplikací onkolytických vakcín. V přehledu jsou uvedeny výsledky ně kte rých klinických studií prezentovaných na ASCO (American Society of Clinical Oncology) 2017. Zajímavá data byla získána z hodnocení dlouhodobé účinnosti imunoterapie u pa cientů, kteří jí museli ukončit pro vznik nežádoucích účinků. Další studie (CheckMate 172) hodnotila bezpečnost a účinnost léčby nivolumabem u pa cientů s MM, kteří selhali v průběhu nebo po terapii ipilimumabem. Značná pozornost byla též věnována účinnosti kombinované imunoterapie u mozkových metastáz. Klíčová slovamaligní melanom -imunoterapie -ipilimumab -nivolumab -pembrolizumab -talimogene laherparepvec -mozkové metastázy SummaryDevelopment of immunother apy has dramatically changed poor prognosis of metastatic malignant melanoma (MM). Inhibition of immune checkpoints represents a new effective treatment. Monoclonal antibodies against CTLA-4 ipilimumab and against PD-1 (programme death 1) nivolumab and pembrolizumab prolong progression free survival and over all survival (OS) in patients with advanced metastatic MM. Both achieved significant improvement in relapse-free survival and OS also in adjuvant setting. It looks like the efficacy of the combined immunother apy of ipilimumab with anti-PD-1 antibodies is superior to the monother apy, but combined ther apy is accompanied by higher toxicity. Management of adverse events of ipilimumab plus nivolumab combination were solved in several clinical trials. New combinations such as immunother apy with intralesional oncolytic vaccination are explored. In this review, some results of clinical trials presented at ASCO (American Society of Clinical Oncology) 2017 are mentioned. Interest ing data were obtained from the evaluation of long-term efficacy of immunother apy in patients who had to stop the treatment for adverse events. Other trial (CheckMate 172) evaluated the safety and efficiency of nivolumab in MM patients who failed on or after ther apy with ipilimumab. Considerable attention has been paid to the efficacy of immunother apy in the treatment of brain metastases. Key wordsmalignant melanoma -immunother apy -ipilimumab -nivolumab -pembrolizumab -talimogene laherparepvec -brain metastases Autorka...

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Overall survival (OS) and safety results from a phase 3 trial of ipilimumab (IPI) at 3 mg/kg vs 10 mg/kg in patients with metastatic melanoma (MEL)

Cited by 22 publications

References 0 publications

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, November 30th 2016

Advances in Immunotherapy of Malignant Melanoma

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