Singapore approves new immunotherapy regime for advanced Melanoma

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Every year in Singapore, there are 1,719 and 1,381 cases of skin cancer (including melanoma) in men and women respectively making skin cancer among the top ten most common cancers in both males and females in Singapore(1).

“Patients with metastatic melanoma historically have a very challenging disease. It is one of the most aggressive and resistant cancers in humans. Treatment outcome with standard conventional chemotherapy is poor and prognosis is guarded,” said Adjunct Associate Professor Richard Quek, Senior Consultant and Deputy Head, Division of Medical Oncology, National Cancer Centre Singapore.

In the pink of your health, the immune system has an array of cells working to remove any challenges to the body. This may include bacterial agents, fungi, and viruses. Every day hundreds of cells in the body undergo mutations and act aberrantly. The immune system acts as a front-line defense against the growth of cancer by recognizing these aberrant cells and eliminating them. The body keeps the immune system cells in check using molecules like PD-L1, which acts as an immune checkpoint and turns of aberrant immune attack on normal cells.

Interestingly, cancer cells have co-opted this checkpoint to serve their own needs. In cancer patients, the immune system cells are often unable to recognize cancer cells that express the protein PD-1. This allows cells aberrantly overexpressing PD-L1 to escape detection by the cells of the immune system and proliferate uncontrollably.

Immune checkpoint inhibitors harness the immune system to fight cancer.

The burgeoning interest in harnessing the power of the body’s immune system to fight cancer has led to the development of a new class of drugs termed as immune checkpoint inhibitors. In 2015, a first of its kind (anti-PD-1) immunotherapy was approved by the U.S. Food & Drug Administration as first-line treatment for metastatic melanoma—allowing greater access to this therapy for patients without having to previously receive other prior treatments.

Now, scientists have found that combining two immunotherapy agents may have more treatment outcome benefits for patients. In Singapore, the Health Sciences Authority(HSA) recently approved the first combination immunotherapy for advanced melanoma, including patients for whom surgery is no longer an option or those cases where the cancer has metastasized rapidly. The therapy regimen approved by the HSA combines Bristol-Myers Squibb’s Opdivo(nivolumab) and Yervoy(ipilimumab). This is the first HSA approved combination of immune checkpoint inhibitors.

How does the Opdivo+Yervoy Regimen work?

Opdivo and Yervoy are immune checkpoint inhibitors that target separate, distinct, and complementary checkpoint pathways (PD-1 and CTLA-4). Dual immune checkpoint inhibition targets cancer cells that may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system, shielding the tumor from immune attack. Yervoy stimulates cells that help fight cancer while Opdivo allows these cells to recognize cancer and attack it. The dual mechanism of action results in increased anti-tumor activity.

The approval is based on data from the Phase3 CheckMate-067 trial, in which the Opdivo+Yervoy Regimen demonstrated a greater progression-free survival(PFS) among patients. In this study, patients with previously untreated unresectable (where surgery is no longer an option) or metastatic melanoma were randomly assigned to one of three groups. The groups were treated with a combination of both drugs, nivolumab(Opdivo) along with a placebo or ipilimumab(Yervoy) alone. At a minimum follow-up of 18 months, the median PFS for the Opdivo + Yervoy Regime was superior compared to the other cohorts.

 “Immunotherapy has undoubtedly revolutionized cancer care. The CheckMate-067 study is notable not only for improving progression-free survival and response rates in patients with advanced melanoma, but also as proof of concept that harnessing the power of immune system through separate pathways can be complementary,” said Dr. Zee Ying Kiat, Senior Consultant Medical Oncologist at Parkway Cancer Centre in Singapore. “The approval for combination nivolumab and ipilimumab represents another step forward in improving outcomes for patients with advanced melanoma.”

Opdivo is associated with immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, encephalitis, other adverse reactions; infusion reactions; and embryofetal toxicity1. Please see the Important Safety Information section below, including Boxed WARNING for Yervoy regarding immune-mediated adverse reactions.