Ghassan Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the significance of a recent trial and how the findings can impact the treatment paradigm of HCC.
The study randomized 101 patients to either an embolization using microspheres alone (n = 51) or a chemoembolization using doxorubicin-eluting microspheres (n = 50). In the trial, adverse events occurred with very similar frequency in each group and did not show any type of difference in RECIST response. Median overall survival for the arms was 19.6 months versus 20.8 months, respectively (HR, 1.11; 95% CI, 0.71-1.76;P= .64).
In an interview withTargeted Oncology, Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the significance of the trial and how the findings can impact the treatment paradigm of HCC.
TARGETED ONCOLOGY:With there being no difference between of embolization using microspheres alone and chemoembolization using doxorubicin-eluding microspheres in patients with hepatocellular carcinoma, what does this change in the treatment paradigm of the malignancy?
No doubt that this study has shown no difference between embolization using microspheres and chemoembolization, and obviously it brings into question the current practice of chemoembolization. Nonetheless, as chemoembolization has been an embedded practice all over the world based on the data that was reported originally by Dr. Josep Llovet inThe Lancet,it would be hard to believe that we would be able to change the concept of chemoembolization to bland embolization, just by the data present. I do expect there will be an interest in that data despite being a phase II study, especially from the perspective of adding therapy to embolization down the road where, probably, the chemotherapy component might influence the effect of any added therapy to that treatment.
TARGETED ONCOLOGY:With there being no planned phase III trial, how should oncologists utilize this information?
Obviously as we did the study, we would have everybody acknowledge and apply what we have found, which is using bland embolization. However, we are very realistic and we do understand that probably there will be not much of a change in the current practice of chemoembolization. Despite that, many of our colleagues not only at the location where the study was done, but at other sites are already in use of bland embolization. This emanates not only from this study, but also going retrospectively to the Llovet study published inThe Lancet. At that time there were two randomizations, those being embolization with chemotherapy versus best supportive care and bland embolization versus best supportive care. What they found was that chemoembolization did better than best supportive care and discontinued the study before any outcomes were studied from the bland embolization component.
There are believers in the process, and obviously you would put it into perspective by doing this randomized study. I would say it might remain within the academic interest, but as I mentioned earlier it might also be of interest once we start to combine this form of embolization to other forms of therapy, where maybe the added chemotherapy that we have currently in chemoembolization would be a hindrance rather than helpful.
TARGETED ONCOLOGY:Does the fact that this was a small study population, as well as a single- institution study, impact the meaningfulness of the results?
The study has its own limitations exactly as stated in the question, which is number one that it's a single institution effort. Number two is that it's a randomized phase II study, ie, it's not powered to compare the the two studies, but both of them are compared technically to the historical control with an exploratory perspective of comparing them to each other.
These are definitely limitations that will no question impact the interpretation of these data. Still, the outcome is based on the exploratory comparison and is quite powerful to where we have to acknowledge that the difference between the two arms has value pertaining to the question of chemoembolization in this treatment paradigm.
TARGETED ONCOLOGY:What were some of the adverse events seen with embolization using microspheres alone, and how do they compare to doxorubicin-eluting microspheres-based treatment?
As we saw in the data, there were definitely further side effects noted in the chemoembolization, which was no surprise because of the doxorubicin. Nonetheless, there was no statistical significance to that component. As much as this was noted, I don't think this is a critical component by itself to limit the use of chemoembolization. I think we need to look at the bigger picture of the treatment and the efficacy plus the side effects.
TARGETED ONCOLOGY:Could there be further, non-phase III trial studies done to investigate further efficacy of embolization using microspheres in alternate settings specifically using other combination therapies for patients with HCC?
If anything, we know there have been serious attempts to add sorafenib to the use of chemoembolization as part of what's reported in Dr. Riccardo Lencioni’s study and many others. Unfortunately, so far we haven't seen in any improvements in patients with this combination. However, further combinations are being developed, especially in the field of immunotherapy, and one might wonder if the embolization should be chemo-based or not chemo-based in the event we try to investigate along with immunomodulators or checkpoint inhibitors.
Obviously there will be other reasons as to why we would consider that combination one way or another based on this specific setup.
TARGETED ONCOLOGY:Is there potential for other treatments such as Y-90 resin microspheres to surpass both embolization using microspheres alone, and chemoembolization using doxorubicin-eluting microspheres in efficacy?
That would be, frankly, a totally different question because the community as a whole that deals with the disease has agreed that the indication for Y-90 would be limited to the localized tumor to the liver plus the major vessels, while the embolization processes would apply to the locally advanced disease without vascular involvement. As such, this is like comparing apples and oranges. Nonetheless, a few studies that look into the possibly applying Y-90 in the setting of hepatocellular carcinoma is still to be declared as per randomized setup will reveal, or not reveal, whatever this added therapy might do.