July 23, 2014 2 Comments
In October 2012, we published a study of patients with metastatic NSCLC whose treatment was guided by EVA-PCD laboratory analysis. The trial selected drugs from FDA approved, compendium listed chemotherapies and every patient underwent a surgical biopsy under an IRB-approved protocol to provide tissue for analysis.
The EVA-PCD patients achieved an objective response rate of 64.5 percent (2-fold higher than national average, P < 0.0015) and median overall survival of 21.3 months (nearly 2-fold longer than the national average of 12.5 months).
The concept of conducting biopsies in patients with metastatic NSCLC was not only novel in 2004, it was downright heretical. Physicians argued forcefully that surgical procedures should not be undertaken in metastatic disease fearing risks and morbidity. Other physicians were convinced that drug selection could not possibly improve outcomes over those achieved with well-established NCCN guidelines. One oncologist went so far as to demand a formal inquiry. When the hospital was forced to convene an investigation, it was the co-investigators on the IRB approved protocol and the successfully treated patients who ultimately rebuffed this physician’s attempt to stifle our work.
With the publication of our statistically superior results and many of our patients surviving more than 5 years, we felt vindicated but remain a bit battle scarred.
I was amused when one of my study co-authors (RS) recently forwarded a paper authored at the University of California at Davis about surgical biopsies and tumor molecular profiling published by The Journal of Thoracic and Cardiovascular Surgery. This single institution study of twenty-five patients with metastatic NSCLC reported their experience-taking patients with metastatic disease to surgical biopsy for the express purpose of selecting therapy. Sixty four percent were video assisted thoracic (VATS) wedge biopsies, 16 percent pleural biopsies, 8 percent mediastinoscopies, 12 percent supraclavicular biopsies and 8 percent rib/chest wall resections. Tissues were submitted to a commercial laboratory in Los Angeles for genomic profiling.
The authors enthusiastically described their success conducting surgical procedures to procure tissue for laboratory analysis. Gone was the anxiety surrounding the risk of surgical morbidity. Gone were the concerns regarding departure from “standard” treatment. In their place were compelling arguments that recapitulated the very points that we had articulated ten years earlier in our protocol study. While the platforms may differ, the intent, purpose and surgical techniques applied for tissue procurement were exactly the same.
What the Cooke study did not describe was the response rate for patients who received “directed therapy.” Instead they provide the percent of patients with “potentially targetable” findings (76 percent) and the percent that had a “change in strategy” (56 percent) as well as those that qualified for therapeutic trials (40 percent). Though, laudable, changing strategies and qualifying for studies does not equal clinical responsiveness. One need only examine the number of people who are “potential winners” at Black Jack or those who “change their strategies” (by changing tables/dealers for example) or, for that matter, those who qualify for “high roller status” to understand the limited practical utility of these characterizations.
Nonetheless, the publication of this study from UC Davis provides a landmark in personalized NSCLC care. It is no longer possible for oncologists to decry the use of surgical biopsies for the identification of active treatments.
As none of the patients in this study signed informed consents for biopsy, we can only conclude that the most august institutions in the US now view such procedures as appropriate for the greater good of their patients. Thus, we are witness to the establishment of a new paradigm in cancer medicine. Surgical biopsies in the service of better treatment are warranted, supported and recommended. Whatever platform, functional or genomic, patient-directed therapy is the new normal and the landscape of lung cancer management has changed for the better.