Are New Cancer Drugs Always Better?

Few cancers instill a greater sense of fear in the medical oncologist that metastatic renal cell carcinoma, the most common form of which is known as clear cell cancer. This type of kidney cancer — driven by a mutation in a gene know as VHL — spreads rapidly, metastasizes to almost any and all organs and historically responded to almost no therapies. The development of Interleukin-2 (IL-2) in the 1980s offered a glimmer of hope. Yet, even this breakthrough ultimately yielded complete and durable responses in a mere 10 percent of patients.

By focusing on the hyper-vascular nature of this disease, investigators then developed a second line of defense that attacked the blood supply of these cancers. Following the introduction of Avastin, a number of small molecule VEGF inhibitors were introduced. Most recently, a class of drugs known as mTOR inhibitors gained popularity by providing objective responses and showing evidence of improved survival.

But what happens when all the really “hot new drugs” fail to provide benefit?

This was a question I confronted in a charming, 68-year-old neurologist who traveled to visit me from Stanford University where he received highly appropriate, yet unfortunately ineffective therapy. The patient presented in July 2010 with rapidly progressive kidney cancer that had overtaken his lungs. He was started on oral Sutent (the treatment of choice). His management was complicated by a hemolytic anemia. When I met the patient in October, I was concerned that he could not survive long enough to take on another treatment, no matter how effective it might ultimately prove to be.

As a physician, he beseeched me to study his tumor in the hope of finding any therapy to salvage him from his rapidly deteriorating course. A small biopsy was obtained with the help of one of our surgical colleagues. The results were striking — no evidence of activity for sorafenib, sunitinib (Sutent), nor the Rapalogs (Rapamycin derivatives). In one fell swoop, all of the newest therapies were swept aside with little likelihood of benefit. Despite the established literature, this patient was clearly sensitive to chemotherapeutics. It was evident to me that the treatment outline, a combination of three drugs, could provide meaningful clinical benefit if the patient could tolerate even the most modest associated side effects. With the kind cooperation of the treating physician in Northern California, our recipe was followed to a T.

The treating oncologist pulled no punches in his description of this patient’s prognosis. Nonetheless, he kindly assisted in the management of the treatment we described. While the cancer-related hemolytic anemia raged, and the patient fought for air, the treatments were delivered. Too ill to leave the hospital, his entire first course of therapy was delivered on an inpatient basis.

For several weeks, we anticipated the worst. And then, a phone call from a chipper-sounding patient. Breathing comfortable, his chest x-ray had cleared, his anemia had resolved and he was being readied for discharge. A short time later, an abdominal ultrasound revealed measurable improvement in the kidney cancer, further confirming objective response.

The patient, now home, could not be happier. The excellent outcome is as gratifying as it is unexpected. There is no question that no one else would have given this treatment. And there is further no question that the patient would not be alive today had he not received it. There are many lessons to be learned from this experience. Among them, that every patient deserves the opportunity to get better; that laboratory analyses can identify unexpected options for patients, even with the worst malignancies; that new drugs aren’t always better drugs; and finally, that nothing succeeds like success.