FDA Approval of Y-90 Resin Microspheres Marks a New Chapter for Radioembolization in Unresectable HCC

SIR-Spheres Y-90 resin microspheres have been approved by the FDA for the treatment of patients with unresectable hepatocellular carcinoma (HCC), offering a new option for those with no macrovascular invasion, Child-Pugh A cirrhosis, well-compensated liver function, and good performance status, according to Armeen Mahvash, MD.

The approval was supported by findings from the prospective, multicenter, open-label DOORwaY90 study (NCT04736121), which evaluated Y-90 as first-line therapy for patients with unresectable HCC.1,2 The trial enrolled 100 patients across 18 U.S. centers and met its prespecified coprimary end points, reporting an overall response rate of 98.5% per independent central review and a local tumor control rate of 100%. The median duration of response exceeded 300 days, and the treatment demonstrated a favorable safety profile.

In an interview with OncLive®, Mahvash, an interventional radiologist in the Department of Interventional Radiology within the Division of Diagnostic Imaging at The University of Texas MD Anderson Cancer Center in Houston and co–principal investigator of the DOORwaY90 study, highlighted the clinical significance of this approval, the strength of the efficacy and safety data supporting it, and how the findings are shaping the evolving role of radioembolization in the management of HCC.

OncLive: What is the mechanism of action of the Y-90?

For many years, historically, chemoembolization was the primary choice for treatment of HCC. There’s a recent paper from 2024, demonstrating that now, in the U.S., radioembolization has actually superseded [chemoembolization for early HCC and for transplant-eligible HCC].

There have been a couple of randomized trials in the recent past that demonstrated the benefit of radioembolization over [chemoembolization]. As a result, the use of [chemoembolization] has decreased, while radioembolization use has increased—largely due to years of data showing its benefits. For patients needing tumor control while waiting for transplant, there’s always a waitlist for patients in the United States. Usually, the minimum wait to get listed is 6 months in order to receive exception points. During that time, you need to maintain tumor control, which was historically achieved with [chemoembolization].

There’s now been a paradigm shift with all the new data. For patients who are potentially transplant eligible, or even need downstaging, [which] wasn’t the focus of our study, but we demonstrated that no patients progressed at 1 full year.

What was the rationale for investigating Y-90 in DOORwaY90 study as a first-line treatment approach for patients with unresectable HCC?

There were been multiple prior studies trying [Y-90] in the HCC realm. And unfortunately, the prior studies up to this point have not used, essentially, a more advanced and standardized dosimetry treatment planning. There was no centralized planning. People were doing their own planning for these procedures in these multicenter trials.

One thing that we realized [when] we were planning this trial, which is very important, is that we [needed] a standardized approach that everyone [would adhere] to and [use] a more advanced method that has not been previously used in any prospective study in the United States, which [is called] partition dosimetry treatment planning.

There’s no study previously in the US that has ever done that. There was one study done in France that did randomly assign patients [against] the older, standardized approach vs this more advanced approach, and that study demonstrated benefit for patients. [However], it’s never been done in the US, and obviously for the indication for use in the US, we felt [it was] very important to include this method of dose treatment planning in the study.

With the advent of better technology, we were having virtual meetings with every site. [After] introductory meetings and different discussions once the sites were open, [when] the sites had planned these treatments, we would have virtual meetings with them. We would [upload] images to the cloud, and we would do virtual meetings with each site once they had done the planning portion. Then we would agree upon a standardized method of treatment.

Honestly, radiation oncologists have been ahead of the curve compared to us in their prior treatment plans where they do multicenter studies. With Y-90, this had never been done. For us, it’s [a] huge breakthrough, [establishing that] this is possible.

We met with all sites. We treated all 100 patients [and] had a personalized treatment for each. We would meet with each investigator at each site and with the clinical research team managing the study, and we would go over each patient, go over their treatment planning, come up with a unified treatment plan, and then they would execute the plan.

On top of that, we would verify that what was planned was actually executed in this study—again, something never done in any other prior study [of Y-90]. Once they [completed] their treatments, they would actually get post-treatment imaging. Then we would verify that what was planned was delivered and executed as planned.

We did demonstrate that there were two patients [for whom] the plan was not adhered to due to technical issues on the day of treatment. Part of the study actually allowed for retreatment within 30 days, which we did for those two patients. Both of those patients had complete responses in the response assessment.

What were the key efficacy and safety findings observed, and how do they support the approval of Y-90 in the first-line HCC setting?

[This approach] showed that centralized treatment planning plus verification can yield the best [results]. I was really amazed. The preliminary results of a 98.5% ORR and a 92% CR rate in this patient population, which was obviously much better than we expected.

The interesting thing is that having a 98.5% ORR in a clinical trial almost seems unreal. It seems too good to be true. And I’m a little bit grateful that we didn’t have a 100% response rate because then I think people wouldn’t believe us. It seems, again, a little bit far-fetched because you always have to be a little bit of a skeptic.

However, all the imaging was reviewed centrally at the ACR [by] blinded, independent reviewers. All the imaging for the patients was sent, blinded, to the ACR, which was the independent third party that reviewed all the imaging. These were reviewed by radiologists not affiliated with the study in any way.

All of these different [components] demonstrate the applicability of this methodology and its reproducibility. Then, if you need to retreat somebody, we obviously retreated patients that needed to be retreated, and the results speak for themselves.

All those [findings] exceeded our expectations. We’re obviously very happy, and hopefully this trial will demonstrate that all future studies can be conducted this way. Essentially, this was a feasibility study: can we do centralized planning? We demonstrated we can, and now all future trials using advanced dosimetry treatment planning can be conducted similar to what we’ve done.

Our goal once the final results are in is to educate people. Doing the 100 patients is not enough. We need to go educate physicians all over the US and outside the US on how we did it and how they can do it at their site. Stopping with a study is not enough—there’s a huge educational component that we also have to execute on behalf of our specialty, our physicians, and future patients who need this treatment.

References

1. Sirtex Medical’s SIR-Spheres Y-90 resin microspheres receive FDA approval for the treatment of unresectable hepatocellular carcinoma. News release. Sirtex Medical. July 7, 2025. Accessed October 22, 2025. https://www.sirtex.com/us/news/press-releases/news-item?id=11510
2. SIR-Spheres Y-90 resin microspheres. Prescribing information. July 7, 2025. Accessed October 22, 2025. https://www.sirtex.com/Media/55rprxv2/SSL-US-17%20SIR-Spheres%20US-IFU%20R4.pdf