For Lung Cancer, We've Got the Answer, Now We're Waiting For the Question
As I finished a recent Thursday afternoon clinic, I received a call. The voice was familiar and I recognized it to belong to the husband of one of my former patients. The news, unfortunately, was not good.
Back pain following a skiing accident in December led to an MRI that showed an abnormality in the thoracic spine. He was being admitted to the hospital for evaluation.
Diagnosis: Stage 4 Lung Cancer
Moments later I received a call from his orthopedic surgeon who explained that there was a large mass at the level of the thoracic vertebra # 6 causing progressive neurological symptoms.
We agreed that high-dose dexamethasone was indicated and I offered to see the patient later that day. Upon review, the disease appeared to arise in the upper right lung, but had spread to many bony sites, the most concerning being the 6th thoracic vertebra.
Fortunately, the patient remained stable until the next day when surgery was undertaken, and tissue for our EVA-PCD analysis was provided. We set up a study that included classic cytotoxic (chemotherapy) drugs and combinations as well as targeted agents.
His Functional Profiling Results
The EVA-PCD laboratory findings revealed striking activity for Gefitinib (Iressa), Erlotinib (Tarceva), Afatinib (Gilotrif), and Osimertinib (Tagrisso).
These drugs represent the 1st, 2nd and 3rd generation of agents that target one of the most common driver mutations in lung cancer, the epidermal growth factor receptor (EGFR).
On the other hand, Alectinib and Crizotinib drugs that target the unrelated ALK and ROS-1 mutations were completely ineffective.
At the level of cellular function these EVA/PCD results defined a tumor driven by an EGFR mutation.
Based upon the findings I submitted a prescription for an oral EGFR inhibitor to begin immediately.
The problem being is that it takes 2-4 weeks for gene profile results to be completed and, today, only genomic results can be used to support the use of these drugs.
While we await the genomic profile, still unavailable at time of this writing, we have the opportunity to compare genomic and functional platforms for lung cancer patients:
Genomic (DNA) TestingEVA-PCD (Functional)Turnaround2-4 Weeks5-7 DaysCytotoxic DrugsNOYESCombinationsNOYESSynergy AnalysisNOYESIdentifiesPossibility of ResponseProbability of Response
Before genomic analyses for EGFR even existed, and before we understood why or how drugs like Iressa and Tarceva worked, our laboratory had developed the EVA-PCD TarχGet platform to identify clinical responders for targeted agents at the functional level.
We've Used Iressa for Years
Indeed, several years before the EGFR gene mutations were discovered in 2004/2005, we regularly treated patients found sensitive to Iressa.
As it was difficult to obtain the drug in the US, we would dispatch our patients' family members to Tokyo where they could purchase Iressa and then return to successfully treat their family members, predicated upon our EVA-PCD findings.
In 2007, we reported the use of first-line Iressa and later Tarceva in patients identified by EVA-PCD and provided a response rate of 100% (Nagourney, RA, et al Clinical Responses to EGFr-TKI’s identified by drug-induced cell death in human NSCLC primary cultures. Proc. ASCO, #18184, 2007).
Why is Functional Profiling More Effective?
One important aspect of functional analyses is their biological rigor.
That is, patients with favorable EVA-PCD results not only respond but tend to respond durably.
This reflects the predictive validity of biological measures over gene profiles.
One of my patients who showed synergy for the combination of Tarceva plus Avastin is now rounding her 10th year on EGFR TKI therapy. One would need to look long and hard at clinical programs using gene-driven therapy selection to find 10-year survivors.
We're Waiting For the Question
While I await the results of this patient's genomic profile, I am confident that he will be found EGFR mutation (+) and negative for ALK, ROS1, RAS, B-RAF and c-MET.
Our experience with this patient is one that we encounter increasingly frequently and reflects our ability to interrogate human biology at the level of cellular function, faster, better and more accurately than genomic platforms.
While genomic analysis provides the “possibility of response” the EVA-PCD analysis provides the “probability of response”. Once again we find that: We have the answer, now we are waiting for the question.
As always, I appreciate your thoughts and comments.
Dr. Robert Nagourney, has been internationally recognized as a pioneer in cancer research and personalized cancer treatment for over 20 years. He is a TEDX SPEAKER, author of the book OUTLIVING CANCER, a practicing oncologist and triple board certified in Internal Medicine, Medical Oncology and Hematology helping cancer patients from around the world at his Nagourney Cancer Institute in Long Beach, California. For more info go to NAGOURNEYCANCERINSTITUTE.COM