IL-2 (1998) |
IV or recurrent melanoma |
Determine the short- and long-term
efficacy and toxicity of high-dose IL-2 |
n = 70 → 600,000 or 720,000
IU/kg (IV). Cycle repeated after 6-9 days |
n = 43 / PFS 8.9 months |
(19) |
n = 12 / PFS 12 months |
The results are more lasting for the patients
with good pulmonary, heart and kidney function |
|
IV or recurrent melanoma, without
previous treatment |
Determine the antitumor efficacy of
IL-2 |
n = 24 → 30 mg/kg (IV) for 8
weeks |
n = 9 / PFS 8 weeks |
(21) |
n = 2 / PFS 16 weeks |
Response rate is lower and efficacy in terms of
response rate is comparable to conventional therapies such as DTIC. |
IFNa-2b (1995) ESTG-1684 |
IIB, IIC or III (with or without
lymph node involvement) or recurrent melanoma |
Determine the anti-tumor efficacy of
high-dose IFNa-2b |
n = 143 → 20 million IU/m2, 5
days a week for 4 weeks, followed by 10 million IU/m2, three times a week
for 48 weeks |
The analysis of 7 years of study showed that on
average 1-1.7 years to PFS and 2.8-3.8 years to OS |
(24) |
First agent to show significant OS benefit (more
pronounced benefit in patients with lymph node involvement). |
IFN-PEGa-2b (2011) EORTC 18991 |
IIB, IIC or III (with or without lymph node
involvement) or recurrent melanoma |
Determine the anti-tumor efficacy of higher doses
of PEG-IFNa-2b |
n = 1256 / n = 627 → 6 Hg/kg weekly for 8
weeks, followed by 3 Hg/kg weekly for 5 years |
PEG-IFNa-2b → the risk of recurrence and
death in 7% of patients at 4 years and 13% for patients with nodal
disease. |
(27) |
|
|
Determine the anti-tumor efficacy of low-dose
PEG- IFNa-2b |
n = 1388 → half received 10 million IU/m2,
5 days a week for 4 weeks, followed by 5 million IU/m2, three times a week
for 2 years |
During 2 years of analysis, the results of PFS
were better with the use of high medication doses. |
(28) |
Biochemother apy |
III, IV or recurrent melanoma |
Determine whether the combination of
chemotherapy and immunotherapy might have better efficacy |
Patients were randomized to receive
cisplatin, vin- blastine, and DTIC (CVD) alone or simultaneously with IL-2
and IFNa-2b |
Those who received IL-2 and IFN-2b showed the
slightly higher response rate and PFS than the group that received CVD
alone. |
(30) |
There was no increase in OS or durable
responses. |
Ipilimumab (2011) |
III, IV or recurrent melanoma |
Evaluate the median OS of patients
who received an ipilimumab-containing regimen as compared with a group that
received the gp100 vaccine alone |
n = 403 → ipilimumab 3 mg/kg + gp100
peptide vaccine |
Median OS in ipilimumab + gp100 group = 10
months |
(33) |
n = 137 → ipilimumab 3 mg/kg |
Median OS with ipilimumab alone = 10.1
months |
n = 136 → gp100 vaccine peptide |
Median OS with gp100 alone = 6.4 months |
|
|
Evaluate the average OS with
different doses of ipilimumab |
n = 73 → 10 mg/kg |
OS was 11% at 10 mg/kg, 4.2% |
(34) |
n = 72 → 3 mg/kg |
|
n = 72 → 0.3 mg/kg |
|
|
every 3 weeks for 4 months by IV infusion |
at 3 mg/kg and 0% at 0.3 mg/kg. |
|
Ipilimumab proved more effective at a dose of 10
mg/kg. |
Vemurafenib (2011) |
III, IV or recurrent melanoma, without |
Evaluate average OS with
vemurafenib |
n = 337, 960 mg vemurafenib orally twice
daily |
After 6 months, OS was 84% for vemurafenib and
64% for DTIC |
(36) |
treatment previous |
n = 338 → 1,000 mg/nv* of DTIC, IV, once
every 3 weeks |
Vemurafenib showed a 63% relative reduction in
the risk of death (OS) and 74% in the risk of progression (PFS) as compared
with DTIC |
Dabrafenib |
III or IV, without previous
treatment |
Evaluate the antitumor efficacy of
dabrafenib, another BRAF inhibitor |
Patients were randomized to receive
dabrafenib (n = 187) or DTIC (n = 63) |
Average PFS was 5.1 months with dabrafenib versus
2.7 months with DTIC. |
(39) |
70% → in risk of progression or death
compared with DTIC |
Trametinib |
III or IV |
Cause a stronger response against the
cancer and prevent resistance to treatment, as patients who use vemurafe-nib
eventually develop resistance. |
n = 125 → varying doses of dabrafenib /
trameti-nib |
Average PFS was 10.8 months in this
group, and 15 of 24 patients (63%) achieved either CR or PR. This dosage
(150/2 mg) is being assessed in a phase III randomized trial |
(40) |
Most PFS was achieved in 24 patients receiving
150 mg dabrafenib twice daily and 2 mg trametinib once daily |
Imatinib |
III or IV |
Ascertain the effectiveness of imatinib for
melanoma with Kit gene mutation |
n = 28 → 400 mg of imatinib twice
daily |
The durable overall response rate was 16%, with a
median time to progression of 12 weeks, and mean OS 46.3 weeks. |
(41) |
|
|
|
n = 43 → 400 mg daily until
disease progression or unacceptable toxicity to a mean of 12 months |
41.9% (n=18) CR |
(42) |
30.2% (n=13) SD |
23.3% (n=10) PR |