chemotherapy, and the other half received transarterial radioembolization with Y-90 microspheres.2
The EPOCH trial was a multicenter international Phase 3 trial, which took 10 years to complete due to the complex nature of the procedures. “Conducting drug trials is different from procedure intervention trials,” Dr. Salem said. “In a drug trial, a patient takes a pill, the investigators pull some blood and do CT scans, and watch progress. In a procedure trial we do angiograms, embolize the vessels and then inject the spheres. It’s high-level interventional radiology.”
“There are some who believe that, because the secondary endpoint of overall survival was not met, it reduces the power of the study. However, studies are not designed on secondary and tertiary endpoints. They’re designed on primary endpoints, and we met both primary endpoints. The secondary endpoints are only exploratory.”
At the completion of the study, investigators reached a positive final analysis, with data showing that they had met both primary endpoints—1) the majority of patients enrolled in the trial achieved PFS and 2) hPFS using Y-90 in the second-line setting.3
“There are some who believe that, because the secondary endpoint of overall survival was not met, it reduces the power of the study,” Dr. Salem said. “However, studies are not designed on secondary and tertiary endpoints. They’re designed on primary endpoints, and we met both primary endpoints. The secondary endpoints are only exploratory.”
Riad Salem, MD, MBA, FSIR
Dr. Salem also pointed out that, when it comes to cancer treatments, patients often go on to receive other treatments once they progress—something that investigators cannot control. Several patients in the control arm of the EPOCH trial actually went on to receive Y-90- based treatment, Dr. Salem said—so although they are in the control arm on paper, 13% of patients did cross over. This overlap, as well as additional treatment options, makes the overall survival analysis difficult to attribute. “That’s why we chose a very clean endpoint of PFS. It’s an imaging endpoint that is easy to track,” said Dr. Salem.
Investigators also found the adverse events to be mild, transient and clinically acceptable. “As with any trial, when you add something to the standard of care, you add adverse events,” Dr. Salem said. “We went from 49% in the control arm to 68% in the combination arm, but the medical oncologist who reviewed the data agreed this was no different from any other trial.”
Dr. Salem also encourages those interpreting data to focus on the hazard ratio, not the median. “We had a hazard ratio of 0.69 for PFS and 0.59 for hPFS,” he said. “Those are very compelling hazard ratios.”
All these data, Dr. Salem says, indicate that there is a role for Y-90 in colorectal cancer if IRs find the right window. “Those who support Y-90 will look at this study to see where in the toolbox
they can incorporate this therapy.” In his opinion, Y-90 microspheres would be a good choice for a patient prior to resection, or for patients taking a chemotherapy holiday.
“Sometimes patients just get exhausted with chemotherapy and the impact it has on their bodies,” Dr. Salem said. “They want a holiday from chemotherapy, and so when they ask if there is something they can do to hold their disease off for a time and allow them to recover, this can be a viable option.”
Because Y-90 can be utilized in an outpatient setting with very minimal side effects, it can be a welcome change for patients to safeguard their health while improving their quality of life between chemotherapy treatments.
While there are no plans for a follow-up trial, Dr. Salem is at work with future studies. Through a collaboration with Boston Scientific, Dr. Salem and other investigators have been given designation to study the use of TheraSpheres for brain tumors and plan to investigate their use for prostate cancer as well. Inside the liver, Dr. Salem believes that cholangiocarcinoma and neuroendocrine tumors are two disease states that could benefit from locoregional therapies.
“The outcome of this trial is promising, not just for colorectal cancer but the future of Y-90 as a platform for cancer treatment,” Dr. Salem said.
References
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71(3):209-249. DOI:10.3322/caac.21660.
2. Chauhan N, Mulcahy MF, Salem R, Benson Iii AB, Boucher E, Bukovcan J, Cosgrove D, Laframboise C, Lewandowski RJ, Master F, El-Rayes B, Strosberg JR, Sze DY, Sharma RA. TheraSphere yttrium-90 glass microspheres combined with chemotherapy versus chemotherapy alone in second-line treatment of patients with metastatic colorectal carcinoma of the liver: Protocol for the EPOCH Phase 3 randomized clinical trial. JMIR Res Protoc. 2019 Jan 17;8(1):e11545. doi: 10.2196/11545. PMID: 30664496; PMCID: PMC6354199.
3. Epoch trial design and primary endpoints. Boston Scientific.
bostonscientific.com/en-US/ medical-specialties/interventional-radiology/ interventional-oncology/
epoch-trial.html.
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