Emerging options for the treatment of melanoma – focus on ipilimumab

Figures & data

Table 1 Clinical staging for melanoma

	Tumor width (mm)	Ulceration present	Lymph node metastasis	Distant metastasis
Stage 0	In situ	No	No	No
Stage 1a	<1	No	No	No
Stage 1b	<1	Yes	No	No
Stage 2a	1–2	Yes	No	No
	2–4	No	No	No
Stage 2b	2–4	Yes	No	No
	>4	No	No	No
Stage 3	Any	Yes or no	I/more lymph node	No
Stage 4	Any	Yes or no	I/more lymph node	Yes

Table 2 Summary of outcome measures for two pivotal Phase III trials of ipilimumab

Treatment	Median OS (months) (95% Cl)	OS-HR (95% Cl)	OS-12 (%)	OS-24 (%)	ORR (partial and complete)	DCR (response + stable disease) (%)
Hodi et al^Citation12
Ipilimumab alone 3 mg/kg (n = 137)	10.1 (8.3–13.8)	vs gp100 alone (n = 136): 0.66 (0.51–0.87); P<0.0026*	45.6	23.5	10.9	28.5
Ipilimumab 3 mg/kg + gp100 vaccine (n = 403)	10 (8.5–11.5)	vs gp100 (n = 136): 0.68 (0.55–0.85); P<0.003* vs ipilimumab alone (n = 137): 1.04 (0.83–1.30); P=0.76)	43.6	21.6	5.7	20.1
gp100 vaccine alone (n = 136)	6.4 (5.5–8.7)	–	25.3	13.7	1.5	11.1
Robert et al^Citation13
Ipilimumab 10 mg/kg + dacarbazine (n = 250)	11.2 (9.4–13.6)	vs placebo + dacarbazine 0.72 (P<0.001)*	47.3	28.5	15.2	33.2
Placebo + dacarbazine (n = 252)	9.1 (7.8–10.5)	–	36.3	17.9	10.3	30.2

Note:

* Significant.

Abbreviation: OS, overall survival; CI, confidence interval; ORR, overall response rate; DCR disease control rate; n, number; HR, hazard ratio; OS-12, percentage survival at 12 months; OS-24, percentage survival at 24 months; vs, versus.

Table 3 Comparison of WHO versus irRC staging for metastatic melanoma

	WHO criteria	Immune-related response criteria (irRC)
New, measurable lesions (>5 × 5 mm)	ALWAYS represent PD	Incorporated into tumor burden
New nonmeasurable lesions (<5 × 5 mm)	ALWAYS represent PD	Do not define progression, but preclude irCR
Non index lesions	Changes contribute to defining BOR of CR, PR, SD + PD	Contribute to defining irCR (complete disappearance required)
Complete response	Disappearance of all lesions in two consecutive observations not less than 4 weeks apart	Disappearance of all lesions in two consecutive observations not less than 4 weeks apart
Partial response	≥50% decrease in sum of peripheral diameters of all index lesions compared with baseline in two observations at least 4 weeks apart in the absence of new lesions or unequivocal progression of non-index lesions	≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart
Stable disease	50% decrease in SPD compared with baseline cannot be established nor 25% increase compared with nadir, in absence of new lesions or unequivocal progression of non-index lesions	50% decrease in tumor burden compared with baseline cannot be established nor 25% increase compared with nadir
Progressive disease	At least 25% increase in SPD compared with nadir and/or unequivocal progression of non-index lesions and/or appearance of new lesions (at any single time point)	At least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart

Abbreviations: WHO, World Health Organization; irRC, immune-related response criteria; irCR, immune related complete response; PD, progressive disease; CR, complete response; PR, partial response; SPD, sum of peripheral diameters; SD, stable disease; BOR, best overall response.

HodiFSO’DaySJMcDermottDFImproved survival with ipilimumab in patients with metastatic melanomaN Engl J Med2010363871172320525992

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RobertCThomasLBondarenkoIIpilimumab plus dacarbazine for previously untreated metastatic melanomaN Engl J Med2011364262517252621639810

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