Besides the tremendous growth in unique and paradigm-shifting treatments, one of the biggest game-changing concepts for cancer patients is the notion that every tumor is different. While all cancer cells share certain biological similarities, individual tumors, even within the same type of cancer, exhibit a variety of differences which are becoming increasingly easier to detect using genetic and molecular profiling technologies. Even tumors within the same patient can have distinctly different characteristics, or characteristics within then same tumor which evolve over time. When it comes to cancer treatments, the long-held view that “one size fits all” is slowly being replaced with individualized treatments as part of personalized medicine.
At Massachusetts General Hospital, Dr. Keith Flaherty began testing individual patient tumors for genetic mutations and cell surface proteins he could then use to identify drugs which might be activated by those characteristics. In 2013, he teamed up with the pharmaceutical company AstraZeneca to use computer algorithms to identify combinations of treatments for individual tumors which might otherwise be unknown.
Most cancer patients today are treated with “one size fits all” chemotherapy and radiation treatments based on pivotal Phase III trials which established the current standard of care, even though it is readily established that a large portion of patients may not see any benefit from such treatments. Cancer patients at comprehensive cancer centers with specialized treatment clinics often receive sophisticated genetic and molecular profiling of tumor samples which help determine treatment regimens. In a Boston Globe interview in 2013, Edward Abrahams, president of the Personalized Medicine Coalition, an education and advocacy organization located in Washington, said, “At the end of the day, what we want to do is move away from one-size-fits-all medicine.”
Today Flaherty is the principal investigator for the National Cancer Institute’s Molecular Analysis for Therapy Choice Program (MATCH) phase II trial, which pairs next-generation tumor profiles with existing drugs which target specific genetic mutations. The MATCH trial is open to adult and pediatric patients with refractory tumors—cancers which have not responded to standard treatments and have relapsed.
The trial has already seen some profound successes. As the New York Times reported Feb. 25, many patients have seen their cancers completely disappear with treatments never designed with their type of cancer in mind. Dr. Richard Pazdur, who has been the FDA’s Director of the Office of Oncology Drug Products for the past decade, is watching these successes with great interest. He explains, “Conventional therapy might give a response rate of 10 or 20 percent.” But with individualized treatments, he’s seeing response rates of 50 to 60 percent. Response rates that high lead Pazdur to wonder whether it make sense to do a randomized or Phase III trial. “These are response rates we haven’t seen before in diseases” he says.
The NCI Match trial hopes to sequence the DNA of at least 3,000 tumors, pair each one with a likely drug, and then provide publish the results. The relatively inexpensive cost of DNA analysis is helping to make individualized cancer treatments practical. Other attempts to developed individualized chemo regimens involve chemosensitivity testing which subjects tumor samples to a wide variety of FDA-approved chemo drugs. But genetic and molecular profiling is much more efficient and flexible, theoretically allowing tumor profiles to be tested against the mechanism of any substance, including over-the-counter drugs or even food ingredients.’