The Rational Difference

Poster from Rational Therapeutics Lung Cancer ASCO Presentation

As I mentioned in a previous post, I recently presented “Phase II Trial of Personalized Chemotherapy In Stage IV NSCLC: Clinical Application of Functional Profiling in First-Line Therapy” (Abstract No. 7617; Citation: J. Clin Oncol 28:7s, 2010) at the 2010 ASCO Annual Meeting.

Following are shots of the poster that was presented. I encourage you to leave any comments and/or questions here as I would be pleased to respond to your inquiries.

The Future – EVA-PCD® Platform and Targeted Agents

As I mentioned in my last post, in our presentation at the 2010 ASCO Annual Meeting, we showed clinical response rates were doubled by using the Ex-Vivo Analysis of Programmed Cell Death (EVA-PCD®) platform with standard FDA approved chemotherapeutic agents in NSCLC patients.

If we can achieve these types of results by simply reconfiguring existing drugs, it suggests that the EVA-PCD platform could provide even better results as we introduce larger numbers of active, targeted agents.

One such agent, PF-1066 provided an overall response rate of 64 percent when patients were selected for the EML4-ALK fusion oncogene. This type of approach, the selection of candidates for therapy predicated upon the biology of the patient, is precisely the premise underlying all of our work. While the PF-1066 data was strongly positive, it represented a very select population of lung cancer patients who carry a specific gene profile. Of all NSCLC patients, only 3-4 percent carry this gene. While recognizing targets like EGFR and ALK continue to improve responses, the EVA-PCD platform is capable of identifying patients for response even when the specific underlying genetic mechanism may be less well characterized. The capacity of the EVA-PCD platform to measure global cellular response enables us to select candidates for whom no known genetic predisposition exists.

Lung Cancer Response Rates Double – ASCO Presentation

On Sunday, June 6, 2010, I presented “Phase II Trial of Personalized Chemotherapy In Stage IV NSCLC: Clinical Application of Functional Profiling in First-Line Therapy” (Abstract No. 7617; Citation: J. Clin Oncol 28:7s, 2010) at the 2010 ASCO Annual Meeting. Colleagues received the presentation very well, with hundreds of attendees examining the findings.

The data are very exciting. This trial of 29 patients with metastatic (Stage IV) NSCLC achieved a response that was twofold higher than the national average (62 vs. 31 percent: p=0.0003). More striking was the 50 percent improvement of median time to progression (9.5 months vs. 6 months). And most exciting of all, the very excellent survival data with a median overall survival of 22.3 months compared with the national average of 12 months.

The most interesting aspect of this study is the fact that we utilized the very same chemotherapy drugs that are available to all medical oncologists in the United States. The trial was limited to FDA approved, compendium listed agents with specific indications for NSCLC. As such, we did not apply new classes of drugs, yet doubled the response rate and median overall survival.

The implications of this are staggering, particularly when we consider the impact that targeted agents are having on cancer care. I will explore these implications in the next entry when I discuss such agents.

When it Works, it Works

Despite the toxicities and haphazard administration schedules associated with many chemotherapy combinations, some patients have dramatic responses to therapy. One such patient was seen in consultation today. In September 2009, this 46-year-old gentleman presented with bilateral plural effusions associated with bilateral pulmonary infiltrates, mediastinal adenopathy, ascite, and respiratory failure. He was immediately intubated and stabilized.

His condition was so grave that no one wished to give him any therapy. A medical oncologist consulted and examined the patient’s extremely poor performance status. I was then asked to provide a second opinion. After discussing the findings with the primary oncologist, we agreed to try empiric chemotherapy with a combo known as folfox. Our reasoning was that this young man with adenocarcinoma would stand the greatest chance of benefit from platinum based therapy and that 5FU — though not often used in lung — would have activity both in thoracic and gastrointestinal primaries. This highly undifferentiated neoplasm could not be better characterized to identify a likely site of origin.

Contrary to everyone’s expectations, the patient had a dramatic recovery. He was first weaned off the respirator, then transferred to physical therapy and, finally, discharged for follow up and out patient chemotherapy. Now, seven months later, the patient is back to normal activities. In my discussions with this patient, I suggested he remain on therapy and I made no recommendation that changes or biopsies be considered. It is my belief that this patient is a biological responder. His underlying disease retains the capacity to respond to therapy. For this reason, I encourage the patient to follow up if he shows signs of progression. It is very possible that other classes of drugs can yet provide benefit when necessary. My reasoning is that the patient has a tumor that retains programmed cell death capacity. The selection of therapies in the future may well continue his excellent response. Nonetheless, I would not intervene at this time based on the old saying that “if it isn’t broken, don’t fix it.” My final point in this patient, despite my misgivings about randomly administering therapies, is that cancer therapies can be extremely effective and well tolerated. Our job is to match the most active, least toxic drugs for each patient.