The FDA recently approved Pfizer to market Xalkori (crizotinib), targeted to treat patients with late stage, non-small-cell lung cancer (NSCLC) who express mutations of the anaplastic lymphoma kinase (ALK) gene.^[1]  Concurrently, the FDA has also approved a companion diagnostic test to help determine if the patient expresses the ALK gene mutation.  This represents a rather new and exciting trend in chemotherapy treatment as Xalkori is the 2^nd targeted chemotherapy agent approved by the FDA along with a test this year (Genentech Inc.’s Zelboraf™ used for late-stage melanoma in patients with BRAF V600E mutation was approved along with a companion test in August 2011).

EML4-ALK is a genetic mutation representing the fusion of the echinoderm microtubule-associated  protein-like 4 (EML4) and ALK genes.^[2]   It is estimated that 2-7% of patients with NSCLC have EML4-ALK mutations, representing about 10,000 patients in the United States alone.^[3]   Patients expressing EML4-ALK mutations are resistant to treatment with currently available growth factor receptor inhibitors (ie. Tarceva®, erlotinib), however, it has been shown in clinical trials that treatment with crizotinib (an ALK inhibitor) has improved response rates to nearly 60% of patients, compared to ~10% of patients treated with second line chemotherapy.^[2]   

One of the challenges facing practitioners had been that no standard FDA-approved test for detecting EML4-ALK mutations was available per the NCCN guidelines for NSCLC.  Now with the new FDA approval of the Vysis ALK Break Apart FISH Probe kit as a companion test, providers will now have a gold-standard tool to use in determining patient qualification for this new medication.

One of the issues that will certainly arise is the cost of targeted therapies.  It is estimated that treatment with Xalkori will cost roughly $9600/month.^[4]   This is far out of the financial reach of the vast majority of patients, although Pfizer is currently offering a patient assistance program for uninsured or underinsured patients which may help a greater number of patients have access to the drug.  The high cost associated with this new drug is not unique, either.  The previously mentioned Zelboraf comes with its own steep price tag of $56,400 for a 6-month course of treatment.^[5]   Even considering planned patient assistance programs, it is clear that these new, innovative genomic-based targeted therapies will come at a significant cost, making accessibility to the general population limited at best.  While these therapies surely represent advances in our understanding of the role of genomics in providing patient-specific therapy, only time will tell if the benefits will outweigh the costs enough to continue advancing medicine in this direction.

References

1.       FDA news release.  FDA Approves Xalkori with companion diagnostic for a type of late-stage lung cancer.  Found at:  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269856.htm#.TlzssAv9VpM.email.  Accessed 30 August 2011.

2.       NCCN Clinical Practice Guidelines in Oncology:  Non-Small-Cell Lung Cancer.  Found at:  http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.  Accessed 30 August 2011.

3.       Kwak E, et al.  Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer.  NEJM; 363:1693-1703. 28 October 2010.  Found at: http://www.nejm.org/doi/full/10.1056/NEJMoa1006448.  Accessed 30 August 2011.

4.       ALK Inhibitor Xalkori FDA-Approved:  New Era, with New Challenges.  Global Resource for Advancing Cancer Education.  Found at:  http://cancergrace.org/lung/2011/08/27/alk-inhibitor-xalkori-crizotinib-fda-approved-new-era-with-new-challenges/.  Accessed 30 August 2011.

5.       US FDA approves Roche skin cancer drug Zelboraf.  Thomson Reuters.  Found at:  http://www.reuters.com/article/2011/08/17/roche-zelboraf-idUSN1E77G0BW20110817.  Accessed 30 August 2011.