Adding radiation therapy to systemic therapy for patients with advanced liver cancer can extend overall survival and delay tumor progression without compromising patients’ quality of life, a randomized phase III clinical trial shows. Findings indicate that radiation therapy must be a normal treatment option for patients with liver cancer who’re ineligible for resection and other standard local-regional therapies. Results of the NRG Oncology/RTOG 1112 trial (NCT01730937) will likely be presented today on the American Society for Radiation Oncology (ASTRO) Annual Meeting.

Adding radiation therapy to systemic therapy delayed tumor progression and lengthened survival, without a rise in negative effects. In all regards, the mix of radiation therapy and sorafenib appears more practical than the drug by itself.”

Laura A. Dawson, MD, FASTRO, Study’s Lead Writer

Laura A. Dawson is a professor of radiation oncology on the University of Toronto and a practicing radiation oncologist on the Princess Margaret Cancer Centre/University Health Network in Toronto.

Liver cancers are amongst essentially the most diagnosed cancers and the third leading explanation for cancer death worldwide. Incidence rates of hepatocellular carcinoma (HCC), essentially the most common sort of liver cancer, in america have greater than tripled since 1980, and mortality rates have also risen despite the growing availability of screening and improved treatments for the diseases that increase the chance of liver cancer.

Systemic therapy is the usual of look after patients with HCC who usually are not eligible for surgical resection or other invasive therapies, but a growing variety of studies suggest a advantage of radiation therapy for these patients. The trial led by Dr. Dawson is the primary randomized North American study focused specifically on the role of radiation therapy for these patients.

Participants within the trial included 193 patients (177 eligible for analyses) with recent or recurrent advanced HCC who were ineligible for surgical resection or other local or regional standard therapies on account of underlying clinical aspects or because their cancer had returned after standard therapy. Most patients had invasion of their cancer into the hepatic vasculature (a poor prognostic factor), and a small number had metastases outside of the liver. The median age was 66 years (range 27-84).

Trial participants were randomized at 23 sites within the U.S. and Canada to receive either sorafenib alone or stereotactic body radiation therapy (SBRT) followed by sorafenib. Sorafenib was the usual systemic therapy when the study began. SBRT was delivered in five fractions over five to 10 days, with total doses between 27.5 and 50Gy, individualized to every patient based on clinical aspects.

Overall survival was longer for patients who received a mixture of SBRT and sorafenib, in comparison with those on sorafenib alone (15.8 vs. 12.3 months; one-sided p = 0.055). The difference was statistically significant after controlling for clinical prognostic aspects reminiscent of performance status and the degree of vascular invasion (p=0.042).

“It was slightly ambitious to design a study with overall survival as the first endpoint, but once we designed the trial, there have been limited systemic therapies available for these patients, and we had strong signals from earlier research that adding SBRT to sorafenib should improve tumor control and result in improved survival,” said Dr. Dawson. “We are able to now say without hesitation that radiation therapy is an efficient treatment for patients with unresectable liver cancer. Outcomes were higher for patients treated with SBRT, despite the planned delay in starting sorafenib.”

Progression-free survival was improved with the addition of SBRT, from 5.5 months with sorafenib alone to 9.2 months with the mix therapy (HR = 0.92, p<0.001). Patients in the mix arm also had longer intervals before their cancers progressed (18.5 vs. 9.5 months; HR = 0.69, p=0.034).

Treatment-related negative effects weren’t significantly different between the treatment groups. 42% of patients on the sorafenib arm and 47% of patients on the SBRT/sorafenib arm experienced severe (i.e., grade 3 or higher) negative effects, and there was one treatment-related death, on the sorafenib-only arm.

While the study was designed to follow patients for five years, Dr. Dawson said that she continues to see longer-term advantages in her clinic. “Some patients who had SBRT on the trial are still returning to my clinic greater than five years after being treated and doing thoroughly.”

The study was closed to accrual sooner than expected, due primarily to a change in the usual systemic treatment for advanced HCC. Prior to 2016, sorafenib was the one FDA-approved first-line treatment for the disease, but since then, several molecular targeted drugs and more recently, immune checkpoint inhibitors have been adopted into the usual of care.

Dr. Dawson said she hopes the findings spark an increased interest in future clinical trials to check the advantage of radiation therapy combined with newer drug therapies. “There’s a growing variety of preclinical and early clinical studies suggesting that SBRT could also be synergistic with immunotherapy, with greater than an additive profit for patients,” she noted.

Other remaining questions include the optimal dosing and sequencing of radiation therapy with different therapies, in addition to the potential advantage of radiation alone for patients who’re ineligible for traditional therapies.

Source:

American Society for Radiation Oncology