Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma: trial

Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma

Population

Previously untreated metastatic melanoma

Design

Randomised (1:1) double-blind phase 3 trial of ipilimumab 10 mg per kilogram plus dacarbazine 850 mg per square metre versus dacarbazine plus placebo, given at weeks 1, 4, 7 and 10, then dacarbazine alone every 3 weeks through week 22; patients with stable disease or response received ipilimumab or placebo every 12 weeks as maintenance. Primary end point overall survival. The registry record lists 681; the paper randomised 502.

Primary endpoint

Arms

Ipilimumab plus dacarbazine (experimental): Ipilimumab 10 mg per kilogram plus dacarbazine 850 mg per square metre at weeks 1, 4, 7 and 10, then dacarbazine every 3 weeks through week 22, then ipilimumab every 12 weeks as maintenance in eligible patients
Dacarbazine plus placebo (control): Dacarbazine 850 mg per square metre plus placebo at weeks 1, 4, 7 and 10, then dacarbazine every 3 weeks through week 22, then placebo every 12 weeks as maintenance in eligible patients

People

Robert C, senior author Wolchok JD

OSHR 0.72Δ median OS+2.1 monthsΔ 12-month OS+11 points

Show the numbers

Results reported for Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma
Endpoint	Analysis	Ipilimumab plus dacarbazine	Dacarbazine plus placebo	Effect
OSRandomised population as described in the abstract (analysis population not stated there)	primaryRobert 2011	median 11.2 months; 47.3% at 12 mo; 28.5% at 2 y; 20.8% at 3 y	median 9.1 months; 36.3% at 12 mo; 17.9% at 2 y; 12.2% at 3 y	HR 0.72P<0.001Hazard ratio for death. The abstract gives no confidence intervals. Grade 3 or 4 adverse events: 56.3% with ipilimumab plus dacarbazine versus 27.5% with dacarbazine plus placebo (P<0.001).

Results reported for Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma
Endpoint	Analysis	Ipilimumab plus dacarbazine	Dacarbazine plus placebo	Effect
OSRandomised population as described in the abstract (analysis population not stated there)	primaryRobert 2011	median 11.2 months; 47.3% at 12 mo; 28.5% at 2 y; 20.8% at 3 y	median 9.1 months; 36.3% at 12 mo; 17.9% at 2 y; 12.2% at 3 y	HR 0.72P<0.001Hazard ratio for death. The abstract gives no confidence intervals. Grade 3 or 4 adverse events: 56.3% with ipilimumab plus dacarbazine versus 27.5% with dacarbazine plus placebo (P<0.001).

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Ipilimumab plus dacarbazine (experimental)
Dacarbazine plus placebo (control)

Data table (modelled values)

Months	Ipilimumab plus dacarbazine	Dacarbazine plus placebo
0	100.0%	100.0%
10	54.1%	44.3%
19	33.8%	22.4%
29	24.5%	14.6%
39	20.8%	12.2%

Appears in

2010 Ipilimumab: anti-CTLA-4 survival trials and FDA approval (2010-2011)

Sources

Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517-26.
PubMed DOI