There is some good news for patients with advanced melanoma as results from a two-year study were announced on April 19th, 2016, by Michael Postow, MD, at the 2016 AACR Annual Meeting. A combination of ipilimumab and nivolumab has shown a 42% improvement in the overall survival (OS) compared with ipilimumab monotherapy.
The results of a two-year assessment of the phase II CheckMate-069 trial have sparked enthusiasm among the patients and the clinicians, as a fifth of people with advanced disease exhibited no sign of tumors in their body after treatment with the combination therapy.
In patients with BRAF wild-type melanoma, the two-year OS rate with the combination was 69% compared with 53% for ipilimumab alone.
“The results of the study are very encouraging,” say the cheered UK doctors leading the trial.
The drug combination is designed to enhance the immune response to the cancer. The immune system is a powerful defense against infection, tumors and invading organisms but there are several “brakes” that prevent the immune system from attacking its own organs. A malignant tumor or cancer takes advantage of these natural glitches and begins spreading from one part of the body to another.
Ipilimumab and nivolumab are designed to “bridge” the gaps in the immune system.
Both drugs work remarkably well in combination than when given alone. For this reason, they have become standard therapies in melanoma.
The results of the study were announced by Michael Postow, MD, at the 2016 AACR Annual Meeting yesterday. In the phase II study, a total of 142 patients with unresectable stage III or metastatic stage IV melanoma were given a combination of ipilimumab and nivolumab or placebo once every three weeks for four doses. This was followed by nivolumab or placebo every two weeks. At the end of the 11-month follow-up, the combination arm of the patients showed 61% objective response rate (ORP) compared with 11% in ipilimumab monotherapy arm. With a two-year follow-up, the tumor burden rate (TBR) was decreased by 70% among the patients randomized to combination treatment compared to the 5% increase in the TBR among all the patients randomized to ipilimumab.
“Eighty percent of responses to the combination (45 of 56) and ipilimumab monotherapy (4 of 5) were ongoing at the two-year follow-up. The majority of these responses happened early, at the time of the first scan,” said Postow. “The median time to response was 2.8 months in the combination arm and 2.7 months for ipilimumab alone.”
Moreover, the patients among the combination arm showed a 54% two-year progression free survival (PFS) compared with 11% with ipilimumab alone.
“This reflects a 64% reduction in the hazard of progression or death in this all-randomized patient population, which is very impressive and statistically significant [P <.0001],” Postow said.
Overall, 70% in the monotherapy arm and 35% of patients in the combination arm received any subsequent therapy.
However, treatment-related adverse events were severe with the combination compared with monotherapy and included gastrointestinal, and hepatic adverse events of any grade which led to the discontinuation in 37% of the patients treated with the combination regimen compared with 9% for ipilimumab alone.
Nonetheless, Dr James Larkin, who ran part of the study at the Royal Marsden Hospital in London is encouraged by the results and is hopeful to work on the benefit of these treatments in the longer term. “It is a relatively small study,” he says. “We are pleased with the results but have a long way to go.”
Meanwhile, Dr Postow and team are looking forward to the further information on survival outcomes with nivolumab plus ipilimumab that will come from the larger randomized phase III of the CheckMate-067 trial.
More good news is expected to pour in from a separate and much larger on-going trial involving nearly 1,000 patients being treated with the combination immunotherapy.
Melanoma is the deadliest form of skin cancer that does not affect skin only but has a tendency to spread to eyes, scalp, nails, feet, mouth and any other part of the body. It is more common in men aged 50 and above.
The disease is more prevalent in whites; every one in 50 Caucasians is at a lifetime risk of developing cancer.
The most common cause of melanoma is exposure to UV light and sunlight. The best way to protect from melanoma is to protect your skin from the harmful rays and undergo regular skin exams.
Other Melanoma Studies And Drugs
Data from another melanoma study on pembrolizumab has shown a 35% increase in survival rate in patients with advanced melanoma. A third of patients treated with the humanized antibody lived for 12 months with no sign of the tumor growing. The drug works by harnessing the immune system i.e., it targets the programmed cell death 1 (PD-1) receptor which is thought to limit the immune system response to the melanoma.
The results of an early stage trial were published in the Journal of the American Medical Association.