Healthcare with Confidence
A Personalized and Effective Approach to Advanced Melanoma Treatment
Targeted therapy is one of the most important advancements in modern melanoma treatment. It works by interrupting specific genetic mutations and pathways that allow melanoma cells to grow and spread. For many patients with advanced or metastatic melanoma, targeted therapy can prolong life, slow disease progression, and improve quality of life.
How Targeted Therapy Works
Targeted therapies are designed to attack specific molecules involved in the growth and survival of cancer cells—particularly those with mutations in the BRAF gene, found in approximately 40–50% of patients with melanoma.
The BRAF V600E mutation, which accounts for about 70–80% of these cases, causes cells to divide uncontrollably. Drugs that block the BRAF and MEK proteins (which are part of the same growth pathway) help to stop this uncontrolled growth.
Unlike chemotherapy, which affects all rapidly dividing cells (including healthy ones), targeted therapies are selective, aiming to preserve healthy tissue while fighting cancer.
Prof. Jacob Schachter, Head of the Ella Lemelbaum Melanoma and Immuno-Oncology Institute at Sheba Medical Center, is a world-renowned leader in melanoma treatment. Under his guidance, targeted therapy protocols are constantly updated based on the latest research and international guidelines.
Prof. Schachter – Head of Melanoma Institute – Consultation Online
Who Can Benefit from Targeted Therapy?
Targeted therapies are primarily used for:
- Stage 4 melanoma (metastatic melanoma)
- Locally advanced melanoma when surgery is not an option
- Patients with a confirmed BRAF mutation, detected via biopsy or surgical tissue analysis
These treatments are typically offered orally (as tablets) and can often be taken at home, with regular monitoring by your oncologist.
Drugs Approved for Targeted Therapy in Melanoma
Here are some of the FDA-approved and widely used medications in Israel’s leading oncology centers:
BRAF and MEK Inhibitor Combinations
- Dabrafenib (Tafinlar®) + Trametinib (Mekinist®)
- Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®)
- Encorafenib (Braftovi®) + Binimetinib (Mektovi®)
These combinations have been shown to significantly improve progression-free survival in BRAF-mutant melanoma.
Individual Targeted Agents
- Vemurafenib (Zelboraf®) – BRAF inhibitor
- Dabrafenib (Tafinlar®) – BRAF inhibitor
- Trametinib (Mekinist®) – MEK inhibitor
- Cobimetinib (Cotellic®) – MEK inhibitor
- Encorafenib (Braftovi®) – BRAF inhibitor
- Binimetinib (Mektovi®) – MEK inhibitor
- Lenvatinib (Lenvima®) – Multi-kinase inhibitor (used in combination regimens)
- Ipilimumab (Yervoy®)* – CTLA4 inhibitor
These drugs are usually taken as pills and have become a cornerstone of personalized melanoma treatment.
Advanced Melanoma: Combination Treatment Options
Targeted therapy is often used before or after immunotherapy, depending on the response. In some cases, combinations of targeted therapy + immunotherapy are part of evolving clinical protocols, especially in treatment-resistant cases.
Interferon Alpha
For high-risk melanoma patients post-surgery, interferon alpha is an older form of biological therapy used to reduce the risk of recurrence. It is administered via subcutaneous injection.
Combination therapies have become a key strategy in treating advanced or metastatic melanoma. By using two medications that work through different mechanisms, oncologists can achieve stronger and more durable responses in many patients, especially those who may not respond to single-drug treatments.
Two of the most widely used combinations in Israel and worldwide are:
- Keytruda® (Pembrolizumab) + Lenvima® (Lenvatinib)
Immunotherapy + Targeted Therapy
This is a powerful mix of an immune checkpoint inhibitor (Keytruda) and a targeted therapy drug (Lenvima) used in certain cases of advanced melanoma, especially for patients with non-BRAF mutations or those who have not responded to other therapies.
- Keytruda (Pembrolizumab): An anti–PD-1 immunotherapy that helps the immune system recognize and destroy melanoma cells.
- Lenvima (Lenvatinib): A tyrosine kinase inhibitor (TKI) that blocks the growth of new blood vessels (angiogenesis) that tumors need to grow, and also interferes with signals that drive cancer cell growth.
Keytruda reactivates the body’s immune response, while Lenvima weakens the tumor’s defenses and limits its blood supply. The combination enhances immune activity in the tumor environment and may lead to better outcomes.
Who is it for?
- Patients with unresectable or metastatic melanoma
- Patients who do not have BRAF mutations
- Patients who have progressed after prior treatments
2. Opdivo® (Nivolumab) + Yervoy® (Ipilimumab)
Dual Immunotherapy
This well-established dual immunotherapy combines two checkpoint inhibitors with complementary mechanisms.
- Opdivo (Nivolumab): An anti–PD-1 antibody that restores immune system activity against cancer cells.
- Yervoy (Ipilimumab): An anti–CTLA-4 antibody that activates T-cells (a type of immune cell) to attack cancer more effectively.
This combination amplifies the immune system’s response to melanoma in different ways. Yervoy initiates a broad immune response, while Opdivo maintains and strengthens it over time.
Who is it for?
- Patients with metastatic melanoma (Stage IV)
- Patients with brain metastases
- Younger or fit patients who can tolerate stronger immune activation
- Often used as a first-line treatment in eligible patients
In some cases, these combinations are used after failure of targeted therapy (BRAF/MEK inhibitors) or when patients are not candidates for such treatments.
- The Opdivo + Yervoy combination tends to cause more immune-related side effects, but can lead to longer-lasting remission.
- The Keytruda + Lenvima combination has shown promise in multiple types of advanced cancers, including melanoma, particularly in clinical trial settings.
Effectiveness and Long-Term Outlook
Around 20% of patients show long-term response to targeted therapy, with durable remission lasting 5 years or longer
However, resistance can develop after 12–18 months, which is why treatment is often adjusted to immunotherapy or clinical trial options
Treatment recommendations are personalized based on:
- Genetic mutation testing (e.g., BRAF, NRAS)
- PET/CT or MRI imaging
- Biopsy and pathology results
You can request an online consultation with Prof. Schachter or one of our senior Israeli oncologists to receive a second opinion or full treatment plan.
Take the First Step: Accurate Diagnosis
Targeted therapy only works if the right mutation is identified. Our team will help you arrange:
- BRAF mutation testing
- Second opinion pathology
- Remote review of scans and biopsy slides
Contact Us Today
To learn more about your options for targeted therapy, get in touch with us to:
- Arrange a consultation with a melanoma specialist
- Get a second opinion on your current treatment
- Receive personalized treatment recommendations based on the most current international guidelines
