- In a phase III, randomized prospective trial, Hodi et al:
- Evaluated 676 patients who received ipilimumab, ipilimumab plus a peptide vaccine, or peptide vaccine alone
- Overall response and disease control:
- Were highest in the ipilimumab alone cohort
- Median OS was:
- 10.1 months for this cohort and overall response was 10.9%
- Disease control was:
- 28.5%:
- With 60% of the ipilimumab cohort having a significant response at 2 years
- In March 2011, the FDA approved ipilimumab as a second-line treatment for metastatic melanoma
- 28.5%:
- A subsequent study demonstrated the benefit of ipilimumab in the first-line setting:
- In a phase III, double-blind clinical trial of 502 metastatic melanoma patients randomized to ipilimumab plus dacarbazine versus placebo plus dacarbazine by Robert et al:
- The ipilimumab cohort was associated with a significantly higher:
- OS:
- 11.2 months vs. 9.2 months
- Durable response:
- 19.3 months vs. 8.3 months
- OS:
- The ipilimumab cohort was associated with a significantly higher:
- For patients with metastatic melanoma:
- The currently approved ipilimumab dose is 3 mg/kg by intravenous infusion given every 3 weeks for four doses
- In a phase III, double-blind clinical trial of 502 metastatic melanoma patients randomized to ipilimumab plus dacarbazine versus placebo plus dacarbazine by Robert et al:
- The clinical use of PD-1 blocking antibodies has been tested in several clinical trials, including a phase I trial of 296 patients with either advanced melanoma or other solid tumors:
- Treatment with a monoclonal antibody targeting PD-1 (nivolumab):
- Was associated with a 28% response rate in patients with metastatic melanoma
- Long-term responses longer than 1 year in 50% of responders
- Anti–PD-1-based therapy was associated with a lower rate of grade 3 or 4 adverse events compared to ipilimumab
- Treatment with a monoclonal antibody targeting PD-1 (nivolumab):
- Additional clinical trials have been performed (NCT01295827 / NCT01704287), including a phase III trial with over 500 patients with metastatic melanoma whose disease was refractory to CTLA-4 blockade:
- In this trial (KEYNOTE-002), patients were randomized to pembrolizumab (2 mg/kg every 3 weeks), pembrolizumab (10 mg/kg every 3 weeks) or chemotherapy (carboplatin plus paclitaxel, paclitaxel alone, dacarbazine, or temozolomide per institutional standard):
- PFS was the primary endpoint and was significantly improved with both pembrolizumab arms compared to chemotherapy:
- 6-month PFS was 34%, 38%, and 16% for pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, and chemotherapy, respectively
- PFS was the primary endpoint and was significantly improved with both pembrolizumab arms compared to chemotherapy:
- Toxicity was limited in this trial; the most common adverse events included fatigue, pruritus, and rash:
- Grade 3 immune-related adverse events (IRAEs) were seen in two patients treated with pembrolizumab 2 mg/kg (hepatitis, hypophysitis) and in eight patients who received pembrolizumab 10 mg/kg (hepatitis, colitis, pneumonitis, and iritis/uveitis)
- Grade 3 immune-related adverse events (IRAEs) were seen in two patients treated with pembrolizumab 2 mg/kg (hepatitis, hypophysitis) and in eight patients who received pembrolizumab 10 mg/kg (hepatitis, colitis, pneumonitis, and iritis/uveitis)
- In this trial (KEYNOTE-002), patients were randomized to pembrolizumab (2 mg/kg every 3 weeks), pembrolizumab (10 mg/kg every 3 weeks) or chemotherapy (carboplatin plus paclitaxel, paclitaxel alone, dacarbazine, or temozolomide per institutional standard):
Rodrigo Arrangoiz MS, MD, FACS, FSSO 