David R. Gandara, MD
Professor of Medicine
Division of Hematology and Oncology
Director, Thoracic Oncology Program
Associate Director, Clinical Research UC Davis Cancer Center
Roy S. Herbst, MD, PhD
Chief of Medical Oncology
Associate Director, Translational Research, Yale Comprehensive Cancer Center
Smilow Cancer Hospital at Yale-New Haven, Yale School of Medicine
New Haven, CT
The expansion of testing for genetic abnormalities in patients with advanced lung cancer is generating questions about which patients’ tumors should be tested, how they should be tested, and whether they should be retested.
In separate interviews, David R. Gandara, MD, and Roy S. Herbst, MD, PhD, the program directors for the 13th International Lung Cancer Congress, provided their thoughts on these questions.
Which patients should be tested?
Whom to test is debatable among different people. To be most cost-effective, you could say I’m only going to test never-smoking patients with adenocarcinoma, and I’m going to test only for the EGFR
mutation and ALK
fusion. On the other hand, more and more, and I see this almost every week in my own practice, I have a patient who is a former smoker or a light smoker, and that patient turns out to have an ALK
fusion or an EGFR
So I think, from an individual patient standpoint, it could easily be reconciled to test every patient with adenocarcinoma, and that’s what the new guidelines from the International Association for the Study of Lung Cancer and the College of American Pathologists will say.
In addition, we can say that some patients with squamous cell carcinoma have enough actionable abnormalities for which to test. I have several of my own patients, for example, who are never-smokers who have squamous cell carcinoma, including young Asian women, and they’ve turned out to have EGFR
-activating mutations. And I can tell you their cancers are clearly squamous cell carcinoma.Herbst:
In my opinion, everyone who has advanced nonsmall cell lung cancer should be tested these days with molecular profiling. Certainly, patients with adenocarcinoma will have a host of actionable mutations such as the EGFR
gene mutation, the ALK
translocation, and ROS1
, to name a few. So I think it is In my opinion, everyone who has advanced nonsmall cell lung cancer should be tested these days with molecular profiling. Certainly, patients with adenocarcinoma will have a host of actionable mutations such as the EGFR gene mutation, the ALK translocation, and ROS1, to name a few. So I think it is important to move forward to try to reflex-test all patients.
In the squamous cell patients, I would test them as well. In many cases, tumors are mixed. In many cases, the diagnosis of squamous versus adenocarcinoma is not entirely sound, so it’s my policy to try to test all patients. Clearly, we’re moving toward an era where we’ll discover new targets, and it will be important to test patients so that we can sort them into the right clinical trial.
I wouldn’t worry about whether someone smoked. I would test everyone, smokers and nonsmokers. Certainly, some of the mutations, such as EGFR
mutations, are known to be more common in nonsmokers, but they’re not unheard of in smokers. It also depends on how much someone smoked and when they stopped smoking.
It’s quite clear that clinical characteristics are trumped by the molecular profile.
Which abnormalities or mutations should be included in the testing?
There is a growing percentage of patients with non-small cell lung cancer who deserve molecular testing. The real message is to test simultaneously for the driver or actionable abnormalities, not sequentially.
For patients with non-small cell lung cancer, the most prominent drivers to test for—and where we have appropriate therapies right now—are the EGFR
mutation and ALK