HJAR Jan/Feb 2022

HEALTHCARE JOURNAL OF ARKANSAS I  JAN / FEB 2022 35 AndrewM. Briggler, MD Medical Oncologist CARTI, Inc. not yet able to be targeted pharmacologically, the ever-increasing number that are can be life-changing for patients. Unlike traditional chemotherapy, which typically requires an intravenous infusion in the infusion suite for several hours a day as well as premedication to help alleviate nausea and potential infu- sion reactions, the majority of these newly developed molecularly targeted drugs are available as pills and are often well tolerated with only modest side effects. Additionally, these tests are covered by health insurance plans, and results are usually back within 10 to 14 days. Lung adenocarcinoma, the most common type of lung cancer in both women and non- smokers, is a prime example of howmolecu- lar profiling has led to a complete paradigm shift in how we treat some cancers. Histori- cally, metastatic lung adenocarcinoma was treated with cytotoxic chemotherapy with limited success, and progression of disease was expected in a matter of months. We now recognize that approximately 15% of lung ad- enocarcinomas harbor a mutation in the epi- dermal growth factor receptor (EGFR), and this number is even higher in certainminority populations. We currently have five EGFR inhibitors FDA-approved for EGFR-mutant lung cancers: osimertinib (Tagrisso), erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) and dacomitinib (Vizimpro). Patients who receive these oral drugs initially, rather than chemotherapy, often live for several years. This would have seemed impossible only a few years prior. Other common targetable gene alterations seen in lung adenocarci- nomas areALK rearrangements (present in about 4% of lung adenocarcinomas), MET (3%), ROS1 (1-2%), RET (1-2%) and BRAF (1-3%). All of these also have at least one, if not multiple, targeted therapies available, which can sometimes be used in succession to great effect. Important advances in other cancers have been made as well. For hormone-positive breast cancer, the most common subtype of breast cancer, the mainstay of treatment is estrogen inhibitors, with chemotherapy reserved for later lines of therapy. The re- cent discovery of alpelisib (Piqray), an oral inhibitor of the PIK3CA gene, which is mu- tated in up to 40% of hormone-positive breast cancers, can often delay the need for cytotoxic chemotherapy for an addi- tional year or longer when added to an es- trogen inhibitor. In cholangiocarcinoma, a rare and aggressive cancer of the bile duct, the standard approach has been combina- tion chemotherapy with usually only mod- est effect. Recognition that about 15% of cholangiocarcinomas harbor a mutation in fibroblast growth factor receptor 2 (FGFR2) led to development of an oral inhibitor of FGFR2, pemigatinib (Pemazyre), which was FDA approved in April 2020. While some genetic mutations are seen only in association with a specific type of cancer, others can be found in a wide range of malignancies. NTRK mutations, for ex- ample, can be found in thyroid cancers, sali- vary gland cancers, sarcomas, melanoma, pancreatic cancer, colon cancer, cholangio- carcinoma, lung cancer and breast cancer, among others. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are two oral inhibi- tors of NTRK now in clinical use. As our ability to identify alterations in a cancer cell’s genome and then subsequently develop specific mutation-targeted inhibi- tors continues to advance, I envision a not- so-distant future where we have a menu of multiple oral targeted agents to select from for any given cancer, perhaps even able to completely spare a patient from the toxici- ties of chemotherapy. n Andrew M. Briggler, MD, medical oncologist earned amedical degree from the University ofArkansas for Medical Sciences in Little Rock, Arkansas. He com- pleted a residency in internal medicine at the Mayo School of GraduateMedical Education in Rochester, Minnesota.He completed a fellowship in hematology/ oncology at the University of Arkansas for Medical Sciences in Little Rock.