Dr. Richard Frank—
We have entered an era in cancer medicine in which new therapies are becoming available seemingly on a monthly basis. The reason for this is that tremendous advances in the scientific understanding of cancer and in drug development are enabling researchers to design therapies specifically targeted to cancer cells. Such “targeted” or “biologic” therapies have begun to replace chemotherapy drugs for the treatment of many cancers. This is a good thing, as targeted therapies tend to have fewer side effects than chemotherapy drugs, though they still can have serious side effects. It therefore begs the question, “Have we seen the end of chemotherapy?”
For example, a new era of targeted immune therapies was recently ushered in with the approval of the drug Keytruda for the treatment of advanced melanoma. Keytruda reprograms a patient’s immune system by targeting a molecule called “PD-1,” so that the killer T-cells which are prevented from attacking cancer cells can now engage and destroy them. In chronic lymphocytic leukemia (CLL), new biologics such as Imbruvica and Zydelig are attacking the renegade cells in uniquely specific ways, leading to spectacular outcomes (CLL is still treated with chemotherapy drugs as the initial therapy). Non-small cell lung cancer is treated with targeted oral therapies rather than intravenous chemotherapy when the cells contain a specific genetic mutation (the most common ones being in the genes EGFR and ALK).
On the other hand, some cancers are now treated with a combination of chemotherapy drugs and a targeted therapy, leading to better outcomes than with either therapy alone. For example, Her2 positive breast cancer is treated with traditional chemotherapy drugs plus one or more targeted therapies, such as Herceptin, Perjeta or Tykerb. Metastatic colon cancer is treated with chemotherapy plus a biologic, such as Avastin, Erbitux or Vectibix.
Still, some cancers have not yet benefited from the present revolution. For example, cancers of the esophagus, pancreas, and bladder are still treated only with traditional chemotherapy drugs (and surgery and radiation when appropriate). Brain tumors largely rely on chemotherapy, radiation and surgery for their treatment. And a form of breast cancer called “Triple Negative Breast Cancer” relies only on chemotherapy for its treatment. It is not that researchers have not tried to apply targeted therapies to these cancers; it is just that none have been found effective enough to be used.
In Fighting Cancer with Knowledge and Hope, I compiled a list of those cancers for which targeted therapies exist and those for which only chemotherapy is still being used. The lists are about even in length indicating that about half of all cancers have not yet benefited from the scientific revolution.
Yet there is great hope as new immune therapies targeting PD-1 and other immune targets appear to be effective across a broad range of cancers. Cancers of the urothelial tract (derived from the bladder, ureters and renal pelvis) appear to be highly sensitive to treatment with the new immune therapies. Still, it is likely that the future of cancer therapy will include the use of chemotherapy drugs, but I predict that they will be used differently and as a way to boost the effects of targeted therapies, rather than as the main cancer fighting treatment.
Richard C. Frank, M.D., is director of cancer research at the Whittingham Cancer Center of Norwalk Hospital, medical director of Mid-Fairfield Hospice, and Clinical Assistant Attending at Weill Cornell Medical College. He has been appointed cancer expert for WebMD and was named a “Top Doc” in the New York Metro area by Castle and Connelly.