Targeted Therapies for Cancer

San Antonio—The treatment of cancer is evolving from a largely reactive, empirical approach to a proactive one in which genomic information is used to improve diagnostic accuracy, guide therapeutic choices, and improve patient outcomes, according to a group of investigators who presented at the AMCP meeting. Armada Health Care and the Specialty Pharmacy Association of America sponsored the session.

The investigators, both physicians and pharmacists, came from the University of Texas M.D. Anderson Cancer Center, the University of New England, CVS Caremark, Blue Cross Blue Shield of Michigan, and Diplomat Specialty Pharmacy of Michigan. The session, titled Treating Cancer in the New Age of Precision Medicine, was presented by David Hong, MD, Edward Li, PharmD, BCOP, James R. Lang, PharmD, MBA, Kirby J. Eng, RPh, and Gary Rice, RPh, MS, MBA.

In his history of oncology drug development, Dr. Hong said that as early as 1941, cancer therapies targeted specific molecules. Efficacy has developed to the point where, today, even patients with advanced end-stage disease can respond to appropriately targeted treatment. In early-phase clinical trials of targeted therapies that use molecular matching, response rates were high for the most part. Dr. Hong cited a trial for imatinib targeting the BCR-ABL fusion for chronic myelogenous leukemia (CML) that yielded a 77% response rate, as well as a trial for vemurafenib targeting the BRAF mutation for melanoma that also yielded a 77% response rate.

The impetus for targeting specific therapies to cancer patients’ specific molecular profile came in 2002 when imatinib was approved by the FDA as the first tyrosine kinase inhibitor for CML. The University of Texas M.D. Anderson Cancer Center’s Initiative for Molecular Profiling in Advanced Cancer Therapy study showed that in patients with 1 molecular aberration, matched therapy was associated with a higher complete and partial response rate, longer time to failure (TTF), and longer survival, when compared with treatment without match therapy. Matched targeted therapy was associated with longer TTF compared to their prior systemic therapy in 175 patients with 1 mutation. In multivariate analysis in patients with 1 molecular aberration, matched therapy was an independent factor predicting response and TTF.

As the possibilities for advances in cancer genomic therapies become more realistic, questions and challenges follow. Cancer genomics are extremely complex, and investigators need to further understand how these characteristics may affect the way therapies are designed and tested, according to the speakers. Targeted agents, many of them oral, are increasingly showing up in the drug pipeline, and evidence exists that targeting genetic mutations regardless of tumor type may be beneficial. While molecular profiling is becoming increasingly complex, the costs of molecular profiling platforms are rapidly declining, even as cancer drug development costs increase.

In general, a problem oncology therapies possess is that they take longer to develop than other type of medicine. For example, oncology drugs take a year longer (9.1 years compared with 8.1 years) to move from clinical and approval phases into the pipeline than other kinds of drugs. However, data from the 10 largest drug companies from 1991 through 2000 show that oncology drugs were the least successful subset of drugs among 9 therapeutic areas from first-in-man status to registration—at a 5% success rate compared to an average rate of 11% for all drugs. There is also a “regulatory traffic jam” keeping all therapies—not just oncology drugs—from progressing at a faster rate. Factors include a complex regulatory process including the FDA and other agencies (IRS, Patent Office, Inspector General, Center for Medicare, and Medicaid services) involvement and legal situations (tort laws, HIPAA), in addition to other factors.