Zelboraf Alternatives

Apart from vemurafenib, various other anti-neoplastic drugs that act as Zelboraf alternatives are available presently. These include Yervoy® (whose mechanism of action targets the activation of the patient’s immune system, which is when fully alert can detect and annihilate the malignant tumor growths present within the body). Patients that don’t have the BRAFV600E mutation (wild type) are often receiving Yervoy at all lines of therapy (1st line, 2nd line, 3rd line), instead of reserving these agents for late stages of therapy, which is often the case with new agents. Another Zelboraf alternative is Dacarbazine. Dacarbazine (alkylating agents) (brand names DTIC®, DTIC-Dome®) also known as DIC or Imidazole Carboxamide) operates by binding to the patient’s DNA and hence hinder the growth and replication of the tumor. Immunotherapy (with interleukin-2 (IL-2) or interferon (IFN) works by simply assisting the body’s immune cells (T-lymphocytes identify the abnormal tumor cells and further annihilate them); however Immunotherapy is not efficient in immune-compromised subjects, e.g. HIV-positive AIDS patients. These are antineoplastic chemotherapy drugs, used in the treatment of various cancers, among which malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas hold a great part. Other novel treatments, which may be pursued as a zelboraf alternative, include adoptive-cell therapy of TILs immune cells (tumor infiltrating lymphocytes), combination therapies, increasing use of biomarkers, and novel targeted therapies. The Phase III pipeline currently contains four immune-therapies, three targeted therapies, and one cytotoxic. Following are some of the medications that are intended to be used as zelboraf alternatives:

Zelboraf alternative, Bristol Myers Squibb’s Yervoy, was approved by the FDA in March 2011 and has made a significant impact, particularly in patients, who do not qualify for vemurafenib due to their genetic makeup. Yervoy is a simple drug which acts by activating the patients’s immune system, while Vemurafenib inhibits enzymes called kinases (it is more specific than Yervoy ( by altering fewer pathways). However, if we analyze the comparison between Zelboraf vs Yervoy, it would be worth mentioning that Yervoy (ipilimumab) can cause serious side effects which can lead to death; such as colitis, perforation of intestines, hepatitis and epidermal necrolysis. While vemurafenib gives less severe adverse effects. Conventional thinking is that Yervoy (ipilimumab) may be the best first-line treatment for metastatic melanoma when disease is less advanced, while Roche’s targeted therapy vemurafenib is an obvious choice for BRAF-mutation positive patients with a high tumor burden and risk of dying fast.

Ongoing trials are evaluating combination therapies for the treatment of melanomas and one such therapy is Zelboraf yervoy combination. The combination seems to also block the appearance of squamous tumors – a common side effect observed with vemurafenib. Oncologists have reported a high level rapid yet durable response in patients suffering with an unresectable (inoperable) or metastatic melanoma. Such therapies like Zelboraf and Yervoy or BRAF and MEK inhibitors could help to bridge the gaps in current therapy approaches. By identifying the key trends in the melanoma therapy channel (including development stage, molecular targets, and therapeutic class), we can evaluate key decisions in melanoma clinical trial design regarding patient selection, trial duration, endpoints, and predictive biomarkers.