New Pfizer Lung Cancer Drug Xalkori

A bit of background into clinical trials

and this a very simplified view.

• 1Phase I clinical trials are sometimes the first time a new compound (drug) is put in man. There are pre-clinical studies done generally in an animal population so, hopefully, the new drug is safe to use in humans. But, since it's the first time the drug has gone into a human, the company producing the drug is understandably cautious so Phase I clinical trials are usually very small - some as small as 20 patients or so.
  
  The Phase I clinical trials objective is not to see if the drug works, but only if it is safe to use in humans.
• 2If there are no untoward adverse events (AEs) or serious adverse events (SAEs) seen in the Phase I clinical trials, a larger Phase II clinical trial is the next step in the drug's development plan (there may be more than 1 Phase II study done). Typical AEs which may be seen in an oral drug are things such as nausea, vomiting or fatigue. SAEs are more serious and include things such as deaths, hospitalizations, life-threatening reaction, or congenital anomaly (mutation) in the offspring of participants in the trial.
  
  So, in the Phase II trial, additional AEs are collected and the data is sometimes combined with the AE data from the Phase I study so there is a more comprehensive view of the drug's safety profile.
  
  A Phase II clinical trial is not only looking for safety but is also looking to see what the dosage should be where the maximum benefit is seen in the population without the indicidence of more or different adverse events. This data is collected sometimes by drawing blood and doing analyses of the blood to look and see how the new drug metabolizes (ie, how it works in the body, how long it stays in the body, etc). These blood studies are sometimes known as Pharmacokinetic (PK) or Pharmacodynamic (PD) draws.
  
  So, in Phase II, the drug is shown to have a larger safety profile, the dosage is potentially identified and the development company has an idea whether the drug works or not from the blood draws and other markers such as tumor size.
• 3If the Phase II study (or "studies" - there may be many of them) goes smoothly, a larger Phase III study (or studies) is conducted. The Phase III study is the largest of the group as the company now has an idea that the drug is safe, the dosage is identified, and now, a larger population is needed to see how effective the drug is. Generally, the new drug must be better than the competition on the market (if there is any) or have less side effects to be approved. There must be some benefit over conventional therapy before the FDA will approve a new drug.
• 4The FDA has the ability to approve drugs and then order additional data be collected once the drug is on the market and in a larger population - these studies are called Phase IV and are also know as "post-marketing" studies. Doctors may be asked to call in any AEs or SAEs which occur in the patients for whom they prescribe the drug.

Cancer trial endpoints

• Complete Response or "CR". In a cancer trial, complete response is the best outcome anyone may hope for. CR means that the tumor has disappeared and there are no cancer markers in the body showing that cancer cells are present. A CR patient is considered cured.
• Partial Response or "PR". A PR means that approximately 50% of the tumor is gone yet the cancer remains. It's possible that a PR patient may continue to improve with additional treatment and may one day become a complete responder.
• Progressive Disease "PD". Sadly, someone classified as PD has a cancer which is resisting the protocol treatment. PD means that the original tumor has grown or new tumors have appeared. If you are classified as having PD during the course of a clinical trial, you will probably be stopping the previous treatment and be moved to a different drug or a different treatment.

Xalcori clinical trial data

• 1As mentioned above, the FDA looked at data from 2 different clinical trials of Xalcori. The agency combined the studies' data so that the final population was 255 patients with ALK-positive non-small cell lung cancer.
  
  Pfizer used a few different tools to measure whether the cancer fighting drug worked including measuring tumor response such as discussed in the previous module "Cancer Trial Endpoints." Through this tool, patient's were placed into categories depending on response of their tumors. Every patient hoped to be in the category of "complete responder" - someone whose cancer got smaller and was basically cured of their lung cancer.
  
  When the data for Xalcori was combined, 3 patients were considered complete responders and 132 patients were consider "partial responders." This is a pretty good response for a cancer which is quite fast growing.
• 2The most frequent adverse events for patients in Pfizer's lung cancer drug trial were vision disorder, nausea, diarrhea, vomiting, edema (swelling), and constipation. One or more of these adverse events occurred in 25% of the monitored patients. Not bad considering the adverse events associated with lung cancer...
• 3The human liver is the first place where toxicity to drugs show up and this data follows the norm. 11% of patients showed elevated liver enzymes and 3% were totally discontinued from the trial due to toxicity. What this means is that, if you're on the drug, liver functions should be monitored one a month.
• 4Electrocardiograms (measuring heart rhythms) were also conducted during the Xalcori trials. The outcome of these studies suggest that patients with heart conditions who are prescribed the lung cancer treatment drug should be monitored frequently for changes in their heart rhythms.
• 5It is suggested that Xalcori will cause harm to unborn child so pregnant women should not take the drug.