Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.

By C. Robert, L. Thomas, I. Bondarenko, S. O'Day, J. Weber, C. Garbe, C. Lebbé, J. Baurain, A. Testori, J. Grob and 14 more. New England Journal of Medicine, 2011

4,405 citations recorded by the source corpus.

BACKGROUND Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. METHODS We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. RESULTS Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab-dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab-dacarbazine group. CONCLUSIONS Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.).

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a0ec163e3f8a6a9e37e654e3e9150e3caa066124

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Citations in the corpus

An immune-active tumor microenvironment favors clinical response to ipilimumab (2012, background): “There are a limited number of treatments for metastatic melanoma (MM), and only a few such as IL-2, ipilimumab, and vemurafenib have proven to prolong survival in phase II or III controlled trials [3–6].”
Immune checkpoint blockade: a common denominator approach to cancer therapy (2015, background): “In 2011, ipilimumab was approved in the United States and Europe as therapy for advanced unresectable melanoma based on results from two phase III trials showing significant extensions in overall survival (OS) (Hodi et al., 2010; Robert et al., 2011).”
Combination of CTLA-4 and PD-1 blockers for treatment of cancer (2019, background): “For example, more than 50% of metastatic melanoma patients failed to respond to monotherapy as seen by objective response rates (ORR) for ipilimumab (1016%) and for nivolumab and pembrolizumab (30-40%) [36, 37, 51, 52, 68, 69].”
Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. (2013, background): “(AEs) occurring in ≥15% of patients included pruritus, rash and diarrhea, and most AEs were managed by the drugspecific treatment guidelines [19, 20].”
Myocarditis in Patients Treated With Immune Checkpoint Inhibitors (2018, neutral): “I mmune checkpoint inhibitors (ICI) represent a novel category of drugs that help direct the immune system to recognize and target cancer cells (1,2).”
A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). (2015, background): “53 3 [51, 147]”