PERSONALIZED MEDICINE ALK, EGFR, AND OTHER TESTING              

 

We are entering a period of personalized medicine, where assessment of a person's medical history and genetic background will impact treatment. It wasn't always like this; 20 years ago, the treatment was surgery for stage 1, chemotherapy for stage 4, and would be basically the same at a local hospital as a major research facility.

Today important variations are seen based upon the cancer type (squamous cell, adenocarcinoma) cellular issues (EGFR, ALk positive), (smoking history) and other factors. The goal is obviously to increase your chances of getting the right treatment having the greatest chance of working. Here are my thoughts.

1. Adenocarcinomas  A greatest number of adeno patients have cellular mutations such as EGFR (epidermal growth factor receptor) and ALK and the adeno patient will want to check new treatments.

2. EGFR Positive  Tarceva is an important drug for EGFR positive patients, showing an impressive 60% response rate.  Adeno patients, non-smokers, and light former smokers (less than 15 pack years years smoked x packs per day) are more likely to be EGFR positive.

3. ALK positive  Crizotinib is an important drug for ALK positive patients who are likewise more likely to be non-smokers or light former smokers, with adenocarcinoma. ALk and EGFR are generally mutually exclusive. Combined, they show a substantial percentage of non-smokers will have one of these mutations, and testing makes sense to get the right targeted treatment.

4. Squamous cell patients,  Smokers and ALK or EGFR. Fairly heavy smokers and those with squamous cell tumors are less likely to be EGFR positive or ALK positive. That leads to the question of whether they should be tested and whether insurance will pay for it. Studies of Crizotinib showed a few patients who were smokers or had squamous cell tumors, and similar results with seen with Tarceva (EGFR)

5. Testing   One question is how intrusive is the testing. The best way to get tissue is through a biopsy, but that carries risks as significant surgery. Less but still intrusive is a bronchoscope, which involves securing tissue with local anesthesia and a smaller sampling. Some have studies testing through unintrusive methods. If testing can be done without risks, it makes sense to get a more complete profile.

6. Moderate and heavy smokers and particular mutations  Smokers are more likely to have the KRAS mutation and Cox-2 mutation. KRAS and EGFR are at the opposite ends and one generally has one but not the other.

Anti Cox-2 drugs include Celebrex and the withdrawn drug Vioxx. While Vioxx may pose some long-term risks for heart issues, if it can play a role in attacking cancer, that may be worth long-term potential risk, at least with advanced lung cancer.

7. Anecdotal Evidence
  It is tempting to look at someone else's treatment and say if it works for them, perhaps it will work for me. However, if the genetic profiles and drug efficacy varies, it may be comparing apples and oranges. Thus it is tough to use the 60% response rate of Tarceva for EGFR positive patients, primarily non-smokers and light former smokers, as a basis for using the drug for EGFR negative smokers who have a response rate in the 9-10% range.

Some have justified Tarceva based upon its capacity for disease stabilization and symptom relief. While these are potentially important criteria, they create a risk of having data misinterpreted or even manipulated. Those advocating testing and personalized evaluation can be on the opposite end of drug companies, who for marketing reasons, may want to suggest the widest possible market for their drugs.

8. Second line treatment and personalized evaluation.  Targeted treatments may become ineffective as the tumor restores its aberrant signaling. For EGFR positive patients, the T790 and MET mutations can make Tarceva ineffective. New drugs are being developed to combat resistance and restore effectiveness.

9. Sources  Google Scholar and PUb Med contain almost all medical abstracts and many full articles. It makes sense to research alternatives if possible.

10. Approach with physician  In my view, the patient or family advocate can have an important role with research. Outside a major research facility, a general oncologist may see 100 types of cancer, and cannot be familiar with every new research development if he sees 25 patients per day.

One does need to be respectful and properly deferential. Not, you forget to mention this important drug I found on the Internet, but can I ask you about this particular drug.

11. Overall cure   Perhaps a drug will be developed to combat all types of lung cancer or even all types of cancer. For many, that is unlikely and we see continuing research as identifying particular characteristics for treatments of certain types and subtypes of lung cancer, and addressing parts of this disease.