Atezolizumab (Tecentriq) + Vemurafenib (Zelboraf) & Cobimetinib (Cotellic)
This triplet therapy combines three treatments: the PD-L1 checkpoint immunotherapy Atezolizumab (Tecentriq) with the targeted therapies Vemurafenib (Zelboraf) & Cobimetinib (Cotellic). Tecentriq works by releasing the breaks on the immune system allowing it to attack cancerous cells. Cotellic and Zelboraf work together to shut down specific pathways used by cancer to grow. The mutations targeted by this combination are present in about half of melanoma patients.
The newly approved triplet therapy is intended to enhance patient outcomes by bringing together the benefits of both targeted- and immune-therapies.
What is Atezolizumab + Vemurafenib & Cobimetinib?
Atezolizumab is a PD-L1 drug that promotes the tumor-killing effects of T-cells (white blood cells that help your body fight disease).
Vemurafenib is a BRAF (pronounced bee-raff) inhibitor and Cobimetinib is a MEK (pronounced meck) inhibitor. Both are targeted therapies that help slow the growth and spread of melanoma cells.
How Do Atezolizumab + Vemurafenib & Cobimetinib Work Together?
Your immune system uses certain molecules on immune cells that act as checkpoints to prevent attacks on healthy cells and minimize autoimmune disease. Melanoma cells can sometimes take advantage of these checkpoint molecules to avoid being detected by the immune system.
Atezolizumab blocks the interaction between a checkpoint molecule within T-cells called PD-1 and its receptor found within tumors called PD-L1, which helps protect tumor cells from being attacked by your immune system. Atezolizumab removes the PD-L1 "shield" to allow your immune system to find and attack melanoma cells.
Vemurafenib blocks the activity of a mutated form of a molecule called BRAF. Cobimetinib blocks the activity of a molecule called MEK. BRAF and MEK are protein molecules that are important in regulating cell growth.
The BRAF V600 mutation signals cells to grow abnormally and divide out of control. These cells can become a melanoma tumor. About half of all melanomas have a BRAF mutation.
MEK receives signals from BRAF and other molecules in the cell. In melanoma treatment, researchers have found that blocking BRAF and MEK at the same time is more effective than blocking BRAF alone.
The combination of Atezolizumab + Vemurafenib & Cobimetinib is intended to enhance the effects of PD-L1 based checkpoint therapy with that of BRAF/MEK targeted therapies to improve the efficacy and durability of response.
Atezolizumab + Vemurafenib & Cobimetinib are all systemic medications, which means that the treatments travel through the bloodstream to reach all parts of the body.
Which Patients May Benefit from Atezolizumab + Vemurafenib & Cobimetinib?
In 2020, the U.S. Food and Drug Administration (FDA) approved the use of Atezolizumab + Vemurafenib & Cobimetinib to treat patients with advanced melanoma with a BRAFV600 mutation.
Advanced melanoma includes patients with:
- Stage 3 disease that is unresectable (unable to be completely removed by surgery).
- Stage 4 disease, also known as metastatic (melanoma cells that have spread to organs and other parts of the body).
This combination therapy works only in patients whose melanoma has tested positive for the BRAF mutation. If you have advanced melanoma, your physician will test you for specific genetic mutations by sending a biopsy (sample of cancer tissue from your body) to a special lab for analysis.
How Are Atezolizumab + Vemurafenib & Cobimetinib Given?
Patients receive 840 mg Atezolizumab administered intravenously (into a blood vein) over 60 minutes. Atezolizumab is delivered every two weeks.
Patients take Vemurafenib & Cobimetinib medications orally (swallowing by mouth). The recommended dose of Vemurafenib is 720 mg, twice daily. The recommended dose of Cobimetinib is 60 mg once daily (21 days on and 7 days off).
Patients usually continue to take these medications until they are no longer needed, until their melanoma worsens, or they experience unacceptable side effects. Depending on how you respond to treatment, your physician may adjust your doses.