Next Generation Clinical Trials Should Combine Radiation with Promising New Cancer Drugs

Paul Harari, MD
Dr. Paul Harari

Patients could see powerful benefits if cancer research included more clinical trials that combined radiation with new targeted therapies and immunotherapy drugs, according to a white paper authored by leading University of Wisconsin Carbone Cancer Center researcher Dr. Paul Harari.

Harari, who chairs the UW human oncology department and is the current president of the American Society for Radiation Oncology (ASTRO), was senior author of a paper published this month in

The Lancet-Oncology. He was joined by UW Carbone colleagues Dr. Paul Sondel and Dr. Zachary Morris, as well as scientists from an international list of prestigious cancer research institutions.

The newer cancer drugs commonly target a specific mutation in the cancer or harness the body’s own immune system to attack the cancer.

Paul Sondel, MD, PhD
Dr. Paul Sondel

“Combining radiation and molecular targeting or immunotherapy drugs holds great potential to increase the known cure rates for many patients currently treated with radiation delivered with curative intent,” he says. “However, we have only begun to scratch the surface of how these drugs may be best combined with radiation.”

One challenge is that new cancer drugs are typically studied in patients with advanced, incurable metastatic disease using drug-alone approaches. Radiation, on the other hand, is often given earlier in the progression of cancer (before distant metastases develop) when cure remains a much greater possibility. Adding promising new experimental drugs with radiation for patients with earlier stages of cancer could increase survival rates and thereby lessen the percentage of patients who develop metastases. Another challenge is that adding a new research drug to a patient’s standard cancer care is complex, requiring large and potentially expensive clinical trials to confirm a survival benefit. However, this approach can be very significant for cancer patients when successful.

Zachary Morris headshot
Dr. Zachary Morris

Harari has personal experience in how the combination therapy can pay off. He and colleagues led an international phase III trial published in 2006 that showed how combining the targeted EGFR inhibitor cetuximab with radiation can increase the survival rate of patients with advanced head and neck cancer by 10 percent. This powerful advance is used for many head and neck patients around the world today.

“After those results, I thought we would see a broad series of clinical trials looking at combination radiation/new drug therapy,” says Harari, who notes that while the combination trials with precision medicine have been slow, the pace is accelerating recently with combinations of radiation and new immunotherapy drugs.

“I believe the best place for some of our newest cancer drugs is in combination with radiation,” Harari says. “I think this is where some of the largest gains for cancer patient survival will be found. But we need to be creative with drug development and trial design to achieve this important goal.”

For a more in-depth look at the issue, see ASTRO’s statement.