Precision Cancer Medicines

The purpose of precision cancer medicine is to define the genomic alterations in a cancers DNA that are driving that specific cancer. Cancer used to be diagnosed solely by a visual microscopic examination of tumor tissue and all patients received the same chemotherapy. But now there is no longer a “one-size-fits-all” approach to cancer treatment. Even among patients with the same type of cancer, the behavior of the cancer and its response to treatment can vary widely. By exploring the reasons for this variation, researchers have begun to pave the way for more personalized cancer treatment.

Not all cancer cells are alike

Cancer cells may differ from one another based on what genes have mutations.  Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome.  Currently this “genomic testing” is performed on a biopsy sample of the cancer.

Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be developed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells.

Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.  Precision cancer medicines can be used both instead of and in addition to chemotherapy to improve treatment outcomes.

Precision medicines are being used for the treatment of thyroid cancer and patients should ask their doctor about whether testing is appropriate

BRAF & MEK Kinase Inhibitors: The BRAF and MEK genes are known to play a role in cell growth, and mutations of these genes are common in several types of cancer. Several thyroid cancers may carry the BRAF mutation known as V600E. This mutation produces an abnormal version of the BRAF kinase that stimulates cancer growth. Another mutation known as V600K may also be present. BRAF and MEK inhibitors are precision cancer medicines that block the activity of the V600E and V600K mutations respectively.1,2

  • Zelboraf®(vemurafenib) BRAF V600E kinase inhibitor
  • Tafinlar®(dabrafenib) BRAF V600E kinase inhibitor

MEK inhibitors

  • Mekinist®(trametinib) MEK V600 kinase inhibitor
  • Cotellic® (cobimetinib) MEK V600 kinase inhibitor

Combination Therapy

A combination of a BRAF (Taflinar) and a MEK (Mekinist) inhibitor appears to decrease the emergence of disease resistance that occurs in patients treated with a BRAF mutation.

The US Food and Drug Administration (FDA) has approved Tafinlar® in combination with Mekinist® for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer with BRAF V600E mutation.1

Up to 44 percent of papillary thyroid cancer patients have the BRAF genetic mutation, and studies show that Tafinlar alone or combined with MeKinist are well tolerated by patients, resulting in a 50 to 54 percent response rate among the patients advanced BRAF-mutated papillary thyroid cancer.2

Lenvima® (lenvatinib):  As an oral anti-angiogenic therapy that targets new blood vessel growth, Lenvima® can “starve” cancer of the nutrients it needs to grow. Overall 65% of refractory thyroid cancer patients experienced a partial or complete disappearance of their cancer following treatment with Lenvima®. They survive on average 18.3 months without cancer progression compared to 3.6 months for individuals not treated with Lenvima®.3

Cometriq (cabozantinib) Although medullary thyroid cancers only account for approximately 2-3% of all thyroid cancers they tend to have a somewhat worse prognosis than more common types of thyroid cancer.  Cometriq is a precision cancer medicine – a tyrosine kinase inhibitor. It targets specific biological pathways that contribute to the growth of several types of cancer, including the receptor tyrosine kinase RET as well as MET and VEGFR2. The drug is approved for the treatment of metastatic medullary thyroid cancer.

Nexavar (sorafenib):  Differentiated thyroid cancer is the most common type of thyroid cancer and can often be cured with surgery and radioactive iodine (RAI) treatment. In some cases, however, the cancer is resistant to RAI. RAI-resistant thyroid cancers have had few effective treatment options.

Nexavar is an oral medicine that works by inhibiting certain proteins that contribute to cancer growth. It has been approved for use in patients with locally recurrent or metastatic, progressive differentiated thyroid cancer that no longer responds to RAI treatment because nexavar increased progression-free survival by 41 percent compared to treatment with a placebo.4

Sutent (sunitinib):  Sutent is a targeted therapy that is approved for the treatment of several cancers. It works by inhibiting multiple proteins in cancer cells to limit cancer cell growth and division and is active in the treatment of thyroid cancer.5

PD-1 Checkpoint Inhibitors

Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer.  By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the cancer cells. Checkpoint inhibitors are approved for the treatment of many cancers and are being evaluated in advanced thyroid cancer patients

  • Keytruda® (pembrolizumab)
  • Opdivo (nivolumab)
  • Imfinzi (durvalumab)
  • Tecentriq® (atezolizumab)

Next: Management of Thyroid Cancer

References


1 http://news.cancerconnect.com/fda-approves-tafinlar-plus-mekinst-for-treatment-of-certain-patients-with-anaplastic-thyroid-cancer/

2 http://news.cancerconnect.com/targeted-therapies-show-initial-effectiveness-subset-papillary-thyroid-cancer/

3 Schlumberger M, Makoto T, Wirth L, et al. The New England Journal of Medicine; 372:621-630 February 12, 2015.

4 FDA approves Nexavar to treat type of thyroid cancer. [FDA News Release]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376443.htm

5 Advanced Thyroid Cancer Responds to Targeted Therapy with Sunitinib [press release]. Endocrine Society website. Available at: https://www.endocrine.org/news-room/current-press-releases/advanced-thyroid-cancer-responds-to-targeted-therapy-with-sunitinib.