Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial

Eggermont, Alexander; Chiarion-Sileni, Vanna; Grob, Jean-Jacques; Dummer, Reinhard; Wolchok, Jedd D.; Schmidt, Henrik; Hamid, Omid; Robert, Caroline; Ascierto, Paolo A.; Richards, Jon M.; Lebbe, Célèste; Ferraresi, Virginia; Smylie, Michael; Weber, Jeffrey S.; Maio, Michele; Konto, Cyril; Hoos, Axel; Pril, Veerle de; Gurunath, Ravichandra Karra; Schaetzen, Gaetan de; Suciu, Stefan; Testori, Alessandro

doi:10.1016/s1470-2045(15)70122-1

Cited by 1,111 publications

(772 citation statements)

References 22 publications

Supporting

Mentioning

736

Contrasting

Unclassified

Order By: Relevance

“…Among all adverse events, diarrhea (65%), fatigue (52.5%), pruritus (52.5%), rash (42.5%) and nausea (42.5%) were the most frequent. Notably, the dose used by the authors (10 mg/kg) was higher than that approved by the FDA for metastatic melanoma (3 mg/kg) but similar to the phase III clinical trial that investigated ipilimumab as an adjuvant therapy after complete resection of high-risk stage III melanoma (Eggermont et al 2015). Comparing both studies that used 10 mg/kg of ipilimumab, adverse events leading to discontinuation occurred in 17/40 (42.5%) of patients with ovarian cancer, while the same outcomes were observed in 245/471 (52%) of patients with stage III melanoma.…”

Section: Challenges and Opportunities For Immune Checkpoint Inhibitormentioning

confidence: 89%

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cunha

Marcello

Rocha-Santos

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors. We critically review the literature on preclinical and clinical studies of the immune checkpoint inhibitors as a treatment option for thyroid cancer, ovarian carcinoma, pancreatic adenocarcinoma, adrenocortical carcinoma and neuroendocrine tumors. We present the challenges and the opportunities of using immune checkpoint inhibitors against these endocrine malignancies, highlighting the breakthroughs and pitfalls that have recently emerged.

show abstract

Section: Challenges and Opportunities For Immune Checkpoint Inhibitormentioning

confidence: 89%

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cunha

Marcello

Rocha-Santos

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…15 Recently, anti-CTLA-4 antibodies in the adjuvant setting showed improvement on RFS compared to placebo, although with substantial toxicity. 16 Data on OS are awaited.…”

Section: Introductionmentioning

confidence: 99%

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

et al. 2015

View full text Add to dashboard Cite

Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional metastatic disease who underwent RLND with curative intent. In this retrospective study, 78 melanoma patients with regional lymph node metastasis who underwent RLND received autologous DCs loaded with gp100 and tyrosinase and were analyzed for functional tumor-specific T cell responses in skin-test infiltrating lymphocytes. The study shows that adjuvant DC vaccination in melanoma patients with regional lymph node metastasis is safe and induced functional tumor-specific T cell responses in 71% of the patients. The presence of functional tumor-specific T cells was correlated with a better 2-year overall survival (OS) rate. OS was significantly higher after adjuvant DC vaccination compared to 209 matched controls who underwent RLND without adjuvant DC vaccination, 63.6 mo vs. 31.0 mo (p D 0.018; hazard ratio 0.59; 95%CI 0.42-0.84). Five-year survival rate increased from 38% to 53% (p < 0.01). In summary, in melanoma patients with regional metastatic disease, who are at high risk for recurrence and metastatic disease after RLND, adjuvant DC vaccination is well tolerated. It induced functional tumor-specific immune responses in the majority of patients and these were related to clinical outcome. OS was significantly higher compared to matched controls. A randomized clinical trial is needed to prospectively validate the efficacy of DC vaccination in the adjuvant setting.

show abstract

“…Though imAE onset is variable, most occur during the initial months of therapy [11][12][13][14][15][16]. Whereas imAEs of any grade can occur in up to 90% of patients treated with ICBs as monotherapy [17,20,24,36,42,43,54,56,59,62], the incidence of grade ≥ 3 imAEs can range from 1% to 10% with anti-PD-1/PD-L1 monotherapy [24,43,54,56,59,62] and from 15% to 42% with anti-CTLA-4 monotherapy [17,20,24,36]. Combination therapy with anti-CTLA-4 and anti-PD-1 antibodies is associated with a 40% to 45% incidence of grade ≥ 3 imAEs [24,36].…”

Section: Adverse Events Associated With Icbsmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial

Cited by 1,111 publications

References 22 publications

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Contact Info

Product

Resources

About