ERASur Study Evaluates Total Ablative Therapy Plus Systemic Treatment in mCRC

Kathryn Hitchcock, MD, PhD

The safety and efficacy of adding total ablative therapy (TAT) of all disease sites to standard systemic treatment is being investigated in patients with limited metastatic colorectal cancer (mCRC) as part of the ongoing phase 3 ERASur study (Alliance A022101; NCT05673148).¹

The trial’s primary end point is to assess and compare overall survival outcomes in those who receive TAT plus standard therapy vs standard therapy alone. A hazard ratio of 0.70 or higher is required to provide 80% power with a 1-sided alpha of 5%.

“A lot of people are pursuing a cure in patients whose metastatic disease is discovered when there’s only a few metastases present, but no one has studied whether that works in a formal, randomized controlled setting,” first author Kathryn Hitchcock, MD, PhD, said in an interview with OncLive^®. “The ERASur trial is trying to discern whether using local therapy in the case of limited metastatic disease causes an increase in survival, or possibly even a cure for these patients.”

Retrospective data have shown that the application of aggressive local therapy to isolated metastases has been associated with improvements in long-term survival in patients with oligometastatic CRC. However, there are a lack of data clarifying the optimal efficacy and use of local ablative therapies in patients with limited mCRC who are not candidates for resection or who have additional disease sites beyond the liver or lungs. Moreover, questions about the benefit of extending metastasis-directed therapy to those with extensive disease remain unanswered.

“Until a few years ago, [a patient with] mCRC just went on chemotherapy, and they probably stayed on chemotherapy until the end of their lives,” explained Hitchcock, who is also a clinical associate professor in the Department of Radiation Oncology, University of Florida College of Medicine, University of Florida Health. “We’ve [now] started to realize that there are some people with metastatic disease who are curable.”

The randomized study is enrolling patients with histologically confirmed, newly diagnosed metastatic CRC with no known BRAF V600E mutations, microsatellite instability, and peritoneal and/or omental disease.

Requirements for pre-registration include measurable disease per RECIST v1.1 criteria, treatment with prior systemic therapy for no more than 4 months, a resected/resectable primary tumor, and up to 4 sites of metastatic disease on baseline imaging.

Notably, liver-only metastatic disease is not permitted, and lesions must be amenable for treatment with stereotactic body radiation therapy (SBRT) and/or surgery, and microwave ablation (MWA). SBRT must be administered to at least 1 disease site. Single sites include right and left hemiliver, lobes of the lungs, each adrenal gland, lymph nodes amenable to treatment in a single SBRT field or single resection, and bone metastases amenable to treatment in a single SBRT field.

Patients can register for the study up to completion of 4 months of chemotherapy, provided they meet imaging requirements. Patients eligible for registration must not have progressed during induction systemic therapy, have received between 4 to 6 months of systemic therapy, and have completed prior definitive adjuvant chemotherapy at least 12 months before diagnosis with metastatic disease. Patients could not be eligible to receive a hepatic arterial infusion pump.

“[ERASur] was designed to be a very pragmatic trial…the goal is [to make it] easy for treating physicians to do what they think is best for the patient within each 1 of the arms,” Hitchcock emphasized.

The trial utilizes a group sequential design with 2 planned interim analyses at 25% and 50% of events for futility. Investigators aim to enroll 346 evaluable patients across both arms.

Patients will be randomly assigned 1:1 to receive either TAT plus standard-of-care (SOC) systemic therapy in the experimental arm or SOC chemotherapy alone in the control arm. TAT involves the treatment of all metastatic sites with any combination of SBRT, with or without surgery, and with or without MWA. SOC may include an additional first-line systemic therapy, maintenance chemotherapy, or treatment pause as determined by the treating physician.

Patients in both arms will also undergo computed tomography (CT) scans, magnetic resonance imaging, or positron emission tomography/CT scans throughout the trial. Patients will be followed until disease progression and death.

“After [disease progression], regardless of the arm that they’re in, patients can go back and have local therapy; that’s not off the plate for them,” Hitchcock noted.

Secondary end points of the trial include a comparison of event-free survival and adverse effect profiles between the arms, as well as time to local recurrence in the experimental arm.

“We’re [also] collecting circulating tumor DNA [ctDNA] from these patients, so we’ll be able to expand our understanding of what ctDNA does in patients with CRC before, during, and after treatment,” Hitchcock said. “That has the potential to add to the science of caring for these patients in an important way.”

The ERASur study is actively enrolling patients and is available to all National Clinical Trials Network sites in the United States. The projected enrollment duration for the trial is 4.7 years.

Disclosures: Dr. Hitchcock had no relationships to report.

Reference

Hitchcock KE, Romesser PB, Shi Q, et al. Alliance A022101: A pragmatic, randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: Evaluating Radiation, Ablation, and Surgery (ERASur). J Clin Oncol. 2023;41(suppl 6):TPS3629. doi:10.1200/JCO.2023.41.6_suppl.TPS3629