In a nutshell
This study evaluated the effectiveness and safety of different treatments given after surgery in patients with advanced melanoma. The data showed that nivolumab (Opdivo) plus ipilimumab (Yervoy) was the best treatment regimen in significantly improving overall survival and survival without cancer worsening in these patients.
Melanoma is an aggressive type of skin cancer. It has a high tendency to spread to other parts of the body (metastasis). The standard treatment for advanced melanoma is a combination of immunotherapy, chemotherapy, surgical removal of tumors, and radiation therapy. In patients with more advanced-stage melanoma, the risk of recurrence or metastasis is higher.
To avoid this, patients can be given additional therapy after surgery (adjuvant treatment). Immunotherapy uses the body’s own system to fight against cancer cells. Tumor cells try to avoid death by switching off the immune system. They bind to proteins on the surface of the immune cells such as PD-1/PD-L1 or CTLA-4. Immunotherapy like nivolumab and ipilimumab block these interactions and turn on the immune system to attack and kill the cancer cells.
Dacarbazine (DTIC–Dome) is a chemotherapy drug commonly used as the first treatment for patients with metastatic melanoma. BRAF and MEK are the most common mutated (abnormal) genes in melanoma. These mutations allow tumors to grow at a rapid rate. Using drugs that target these mutations can improve survival. Trametinib (Mekinist) is a drug that blocks MEK. It is important to compare the effectiveness and safety of different treatments given after surgery and evaluate the best treatment regimen in patients with advanced melanoma.
Methods & findings
This study analyzed 9 studies and involved 3077 patients with advanced melanoma. Patients were randomly assigned to receive one of eight treatment approaches after surgery – ipilimumab plus dacarbazine, dacarbazine, ipilimumab, trametinib, ipilimumab plus gp100 (peptide vaccine), gp100, nivolumab, and nivolumab plus ipilimumab.
Nivolumab plus ipilimumab, nivolumab, and trametinib significantly improved overall survival and survival without cancer worsening compared to ipilimumab in patients with advanced melanoma.
Nivolumab plus ipilimumab had the highest probability of being the best treatment regimen in terms of improving overall survival and survival without cancer worsening.
Nivolumab plus ipilimumab had the highest risk of side effects, followed by ipilimumab plus dacarbazine and trametinib. Nivolumab, dacarbazine, and ipilimumab plus gp100 reduced the risk of side effects compared to ipilimumab alone.
Combination therapy was more beneficial to improve overall survival and survival without cancer worsening than monotherapy in advanced melanoma treatment, even if it increased the risk of side effects.
The bottom line
This study concluded that nivolumab plus ipilimumab was the best treatment regimen in significantly improving overall survival and survival without cancer worsening in patients with advanced melanoma. The authors suggested that in order to choose the best therapy, clinicians must consider the effectiveness, side effects, and physical status of the patients.
The fine print
The number of studies analyzed was very small. This study did not include patients with BRAF-mutant cancer. Patients knew which treatment they were getting in two of the studies analyzed, which might affect conclusions.
Published By :
Frontiers in oncology
Jul 06, 2022