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 spoke with Govindarajan Narayanan, MD about his practice becoming the first in the United States to successfully surgically treat a patient with a liver tumor using the Epione robot, as well as the process of transitioning from CT-based image guidance to the robotic workstation in his care.

Narayanan, a professor of Radiology and an interventional radiologist at Miami Cardiac and Vascular Institute and the chief of Interventional Oncology at Miami Cancer Institute, both of Baptist Health South Florida, described how the use of Epione may save significant amounts of time while performing microwave ablation, cryoablation, and irreversible electroporation (IRE). Developers designed the robotic device to simplify several probe procedures, helping make large tumors more predictable to manage.

According to Narayanan, Epione is suitable for use in any patient for whom his practice typically performs image-guided ablations. Additionally, the device may “level the playing field” by allowing those with less experience to give highly accurate surgery, thereby increasing the availability of physicians who can offer these treatments across multiple practices.

Narayanan also described some of the potential challenges associated with adopting the Epione robot in clinic, such as adapting to the physical space that it occupies in the operating room. The device may also pose a steep learning curve with respect to procedures involving multiple needles such as cryoablation and IRE, as it is necessary to set a path that won’t cause any deflections of the needle.

Looking ahead, Narayanan said that future technological developments may allow users to operate the robot remotely, allowing patients to receive surgery at a treatment center even if a practicing physician is not physically present.

“It’s very exciting to be at the forefront of bringing such a cutting-edge technology to mainstream clinical practice,” Narayanan said. “Everything is done with one click, so it saves a significant amount of time. And because you’re not doing multiple check scans when you place the needles, you’re saving on radiation time.”

First patient treated in the United States with Quantum Surgical’s Epione® robot. News release. Quantum Surgical. May 24, 2023. Accessed November 6, 2023. https://shorturl.at/lzH01

Epione. Quantum Surgical. Accessed November 7, 2023. https://shorturl.at/dqyL6

Govindarajan Narayanan, MD, speaks to the potential time-saving advantages of using the Epione robot for microwave ablation, cryoablation, and other surgical strategies in patients with liver cancer and other tumors. 

Adapting to a Robotic Workstation for Image-Guided Liver Cancer Surgery

Transarterial chemoembolization plus sorafenib did not significantly improve overall survival in advanced hepatocellular carcinoma vs sorafenib alone.

Transarterial Chemoembolization Regimen Shows PFS Improvement in HCC

Data from the TALENTACE trial support TACE plus atezolizumab/bevacizumab as an effective option in those with unresectable hepatocellular carcinoma.

PFS Improves With TACE-Based Regimen in Unresectable Liver Cancer

HAIC with oxaliplatin and raltitrexed produced a higher response rate vs other systemic therapy agents in patients with advanced hepatocellular carcinoma.

HAIC Regimen Yields Long-Term Survival in Unresectable HCC

SIR-Sphere Y-90 resin microspheres are the only approved radioembolization treatments in the US for both HCC and mCRC. 

FDA Approves SIR-Sphere Y-90 in HCC

Survival benefits were observed across most post-hoc subgroups treated with anlotinib plus penpulimab, particularly among those with high-risk disease features.

Anlotinib/Penpulimab Enhances Survival vs Sorafenib in Unresectable HCC

Treatment with stereotactic body radiation therapy in combination with sorafenib (Nexavar) bested sorafenib alone among a group of patients with hepatocellular carcinoma, according to recent study results.

The findings, according to Louis Potters, MD, FACR, FABS, FASTRO, mark the first time that radiation has elicited a survival benefit in patients with this type of liver cancer.

 spoke with Potters about those findings, which were from a randomized phase 3 trial (NCT01730937) and presented at the 

2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.

Potters, who is the chair of the Department of Radiation Medicine and deputy physician-in-chief of Northwell Health Cancer Institute in New Hyde Park, New York, said that these findings show that radiation therapy has a role in the treatment of patients with this form of liver cancer.

The NRG 1112 trial was a hepatocellular SBRT trial. That was actually an overall positive survival benefit trial. It's the first time that radiation therapy has been identified to improve overall survival in patients with hepatocellular carcinoma. And although there continues to be an effort in the chemotherapy side of things looking at agents that work well with this particular disease, we've clearly been able to carve out, based on the results of this study, a role for radiation therapy, SBRT in particular, for patients with hepatocellular carcinoma. That was an exciting study to hear about.

Dawson LA, Winter K, Knox J, et al. NRG/RTOG 1112: Randomized phase III study of sorafenib vs. stereotactic body radiation therapy (SBRT) followed by sorafenib in hepatocellular carcinoma (HCC) (NCT01730937). Presented at 2022 American Society for Radiation Oncology Annual Meeting (ASTRO); October 23-26, 2022; San Antonio, TX. Abstract LBA 01.

Adding radiation to sorafenib elicited a survival improvement in a group of patients with hepatocellular carcinoma, a type of liver cancer.

Radiation Shown to Improve Survival in Liver Cancer ‘For the First Time’

Ghassan K. Abou Alfa, MD, an attending physician at Memorial Sloan Kettering Cancer Center, spoke with CancerNetwork

FDA approval of tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) for patients with unresectable hepatocellular carcinoma (HCC)

 about the next steps in managing the disease. In addition to highlighting the progress that has been made thus far in terms of improving outcomes in patients with HCC, he spotlighted future focuses such as advancing treatment with immune checkpoint inhibitors, as well as combining them with local therapies.

We need to cure [HCC] and we still have ways to go. No question that I humbly and proudly have witnessed this disease start from a median survival of barely 3 months, and worked through different studies at Memorial Sloan Kettering for the last 22 years, and look where we are: We're talking about a mean survival of close to 16.5 months or more. There is no doubt that we are on the right track, but of course, we want more. Why do we need more? We owe our patients that and promise them that. Will there be further advancement of the use of checkpoint inhibitors in a more advanced way? Absolutely. Is it also possible to consider local therapy married with the use of the checkpoint inhibitors? By all means, yes. To that extent, our current study, which is already open in some parts of the world will actually combine chemoembolization for local therapy plus the use of durvalumab and tremelimumab, as we just mentioned.

Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News Release. AstraZeneca. October 24, 2022. Accessed October 31, 2022. https://bit.ly/3Fbwx1w

Future research into the management of unresectable hepatocellular carcinoma may involve combining local therapies with checkpoint inhibitors like durvalumab and tremelimumab, according to Ghassan K. Abou-Alda, MD.

Ghassan K. Abou-Alfa, MD, Discusses Next Steps in Researching Unresectable HCC

FDA approval of tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) for the treatment of patients with unresectable hepatocellular carcinoma (HCC),

 spoke with Ghassan K. Abou-Alfa, MD, an attending physician at Memorial Sloan Kettering Cancer Center, about which patients may benefit most from this regimen. Although the combination therapy might not be suitable for those who have received prior transplantation, he highlighted several other patient subgroups with recurrent disease who may derive benefit from the treatment.

The chance for recurrence of [unresectable HCC], even among patients who have a surgical resection is unfortunately very high. Understandably, patients who have received transplants—who hopefully will never have recurrence—might not be the right patients for the use of checkpoint inhibitors because of the transplant and immunosuppression that's already there. Besides that, patients who either have recurrent disease after surgery, locally advanced diseases that will fail local therapy, or those with systemic therapy will all benefit from [durvalumab plus tremelimumab]. This unfortunately is a large number of patients [in terms of] the separation of the different cancer stages. As such, almost every patient will have some opportunity to benefit from that therapy.

Patients with unresectable hepatocellular carcinoma who have recurrent disease following surgery or locally advanced diseases who will likely progress on local therapy may have an opportunity to benefit from tremelimumab and durvalumab following its FDA approval, according to Ghassan K. Abou-Alfa, MD.

Ghassan K. Abou-Alfa, MD, Spotlights Patients With Unresectable HCC Who May Best Benefit From Tremelimumab/Durvalumab 

FDA approval of tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) for the treatment of patients with unresectable hepatocellular carcinoma

, Ghassan K. Abou-Alfa, MD, an attending physician and board certified medical oncologist at Memorial Sloan Kettering Cancer Center (MSKCC), spoke with CancerNetwork

 about the significance of ensuring equal access to treatment for this disease on an international scale. He discussed the current barriers to treatment for hepatocellular carcinoma, especially those observed in developing countries within Africa, and how his team at MSKCC is working to broaden access.

We have to realize that, sadly, some patients who might be eligible for [treatment with tremelimumab and durvalumab] will never see it. The reason is because they will not have access to it. It’s good news that we have this new therapy that we are beyond thrilled to have. Other than further enhancing benefit from the therapy, we have to find ways to ensure that patients get access to treatment. Considering that liver cancer has one of the highest incidences in the continent of Africa, this really tells you how much we still have to do in regard to our lower-/middle-income countries to make sure they get access to therapy. One of the efforts that we have done at Memorial Sloan Kettering [Cancer Center] along with colleagues from Africa last year was to form a committee of 26 physicians from throughout the whole continent. We asked about what therapies were available to about 500 physicians throughout the continent. It’s amazing how limited the access is. This is really what we owe to our colleagues and our patients, wherever they are in the world: better therapy. I am excited but at the same time, it’s a little bit of a wake-up call to make sure that everybody has access.

Ghassan K. Abou-Alfa, MD, discusses the importance of improving access to novel therapies and combinations for patients with hepatocellular carcinoma across the world.

Ghassan K. Abou-Alfa, MD, Discusses Importance of Treatment Accessibility in Unresectable HCC

In an interview with CancerNetwork®, Ghassan K. Abou-Alfa, MD, an attending physician at Memorial Sloan Kettering Cancer Center, spoke about the 

FDA approval of tremelimumab (Imjudo) in combination with durvalumab (Imfinzi)

 for the treatment of patients with unresectable hepatocellular carcinoma.

Abou-Alfa highlighted key findings from the phase 3 HIMALAYA study (NCT03298451) that led to the FDA approval, which showed 31% of patients receiving tremelimumab and durvalumab had an improved 3-year survival period compared with 20% of those who were treated with sorafenib (Nexavar).

 Although more research is necessary to improve the treatment of patients with unresectable hepatocellular carcinoma, he indicated that the newly-approved Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen is a step in the right direction in the management of this disease.

[Hepatocellular] carcinoma is still not a curable disease. As such, it's definitely a cancer with an unmet need, because we did not cure people [only provided an option for treatment]. If anything, the advent of the durvalumab plus tremelimumab [regimen] that we now call the STRIDE regimen based on the HIMALAYA study, is no doubt a step in the right direction for further improvement and survival. However, a response [displayed] can be a complete response and will be [shown] in survival that are matching up to 1/3 of the patients having a 3-year overall survival. This is no doubt a step in the right direction, but by all means, there’s still more work to do.

Abou-Alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab and durvalumab as first-line therapy in patients with unresectable hepatocellular carcinoma: HIMALAYA. 

. 2022;40(suppl 4):379. doi:10.1200/JCO.2022.40.4_suppl.379

Ghassan K. Abou-Alfa, MD, spoke about the recent approval of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma, based on results from the phase 3 HIMALAYA trial. 

Ghassan K. Abou-Alfa, MD, Highlights Approval of Tremelimumab and Durvalumab in Unresectable HCC

CancerNetwork® spoke with Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Comprehensive Cancer Center, at the 

 about the key results and main takeaways to emerge in patients with hepatocellular carcinoma (HCC) who were treated with tremelimumab at 300 mg plus durvalumab (Imfinzi), tremelimumab at 75 mg plus durvalumab, or durvalumab alone vs sorafenib (Nexavar) in the phase 3 HIMALAYA study (NCT03298451).

In the HIMALAYA study, the primary end point was positive showing improved [median overall] survival for the tremelimumab [at a] single dose of 300 mg plus durvalumab of 16.4 months compared with 13.8 for sorafenib, with a hazard ratio of 0.78 [95% CI, 96% CI, 0.65-0.92; 

 = .0035], which is clinically and statistically significant. If anything, the separation of the curve was noticeable around 4 months and started propagating further enough that when we did a landmark evaluation at 9 months, we have seen the hazard ratio improve markedly up to 0.70. That suppression continued at [follow-up] analysis at 18 months, 24 months, and 36 months, enough that by 3 years, 30% of the were still alive with the tremelimumab single dose plus durvalumab.

Now, this brings up an important question in regard to the priming effect that’s needed for [efficacy]. Interestingly, that’s why the PFS [progression-free survival] was totally equal between the 2 arms of tremelimumab single dose plus durvalumab, single-agent durvalumab, and sorafenib. There was no difference at all even though the separation started to be seen afterwards. More importantly, the critical point is that the priming of the T cells happened right away. The time to response was only 2 months for tremelimumab plus durvalumab and close to 5 months for sorafenib. If anything, it tells us one more time that we have been using new science and the new language of checkpoint inhibitors, but we’re still using the old dictionary of median survival and median PFS. I would say here the PFS is not of critical importance. If anything, the improvement in survival is the key player that we have seen not only with HCC but with other diseases such as melanoma, lung cancer, gastric cancer, etc.

Abou-Alfa G, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. 

. 2022;40(suppl 4):379. doi: 10.1200/JCO.2022.40.4_suppl.379

The combination of tremelimumab plus durvalumab improved survival for patients with unresectable hepatocellular carcinoma in the phase 3 HIMALAYA trial.

Ghassan K. Abou-Alfa, MD, Details Survival Data With Durvalumab Plus Tremelimumab in HCC From HIMALAYA Trial

 about the patient population, dosing regimens, and eligibility criteria for enrollment in the phase 3 HIMALAYA study (NCT03298451), which looked at tremelimumab plus durvalumab (Imfinzi) vs durvalumab alone for unresectable hepatocellular carcinoma.

The HIMALAYA study was a randomized, open-label, multicenter study covering patients from all over the world. It included patients like any other studies who are of appropriate performance status, good liver functionality with a Child-Pugh score of A. [They] randomized 1325 patients to 4 arms. The fourth arm of tremelimumab, anti–CTLA-4 at 75 mg given 4 times plus durvalumab, did not fare any better compared to durvalumab as a single agent in Study 22 [NCT02519348] that was already reported in [

 As such, we stopped that arm and continued with 3 arms on the study, the first arm being a single dose of tremelimumab at 300 mg plus durvalumab. This was compared to sorafenib [Nexavar] looking for superiority of overall survival. In addition to that, we did look at single-agent durvalumab compared with sorafenib to look for noninferiority.

Kelley RK, Sangro B, Harris W, et al. Safety, Efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: Randomized expansion of a phase I/II study

. 2021;39(27):2991-3001. doi:10.1200/JCO.20.03555

Ghassan K. Abou-Alfa, MD, examined the trial design of the phase 3 HIMALAYA trial of tremelimumab plus durvalumab for frontline hepatocellular carcinoma, with results presented at the 2022 Gastrointestinal Cancers Symposium.

Ghassan K. Abou-Alfa, MD, Discusses Patient Population and Dosing of PD-L1/CTLA-4 Inhibitor Combo for HCC in HIMALAYA Trial

, about important developments leading to the examination of tremelimumab plus durvalumab (Imfinzi) compared with durvalumab alone for unresectable hepatocellular carcinoma in the phase 3 HIMALAYA study (NCT03298451).

Interestingly, it took a long while to get to this point [of presenting research at the 2022 Gastrointestinal Cancers Symposium]. If anything, I’m humbled to say that I started in the field before any therapy was available. We started with sorafenib [Nexavar], we evolved to [using another tyrosine kinase inhibitor] lenvatinib [Lenvima] in first-line therapy. There’s no question we all were interested in immunotherapy. We were looking forward to that because of the real effects that we anticipated in the setting of hepatocellular carcinoma [HCC] with the hyperimmune effects. Interestingly, the single-agent anti–PD-1 or anti–PD-L1 did not fare that well. If anything, it clearly started evolving the need for certain priming for that entity of the anti–PD-1, anti–PD-L1 effect. We have seen it with VGF or with FGF. HIMALAYA has completely evolved. The anti–CTLA-4 that comes into play as an important, powerful booster extract that comes all the way from the top of the chain in the lymph node itself to further enhance anti–PD-1, anti–PD-L1 activity. This led to the further evaluation of the HIMALAYA study.

Ghassan K. Abou-Alfa, MD, detailed the evolution of treatment options for unresectable hepatocellular carcinoma prior to the phase 3 HIMALAYA study and the reasons for launching the trial.

Ghassan K. Abou-Alfa, MD, on Integral Developments Leading to Phase 3 HIMALAYA Trial in Hepatocellular Carcinoma

The panel discusses adverse effects associated with stereotactic body radiation therapy, and the Oncology Brothers provide a recap of the entire discussion.

Adverse Effects Associated with SBRT in Patients With HCC

Focusing on liver-directed therapy, the panel discusses the treatment of transplant-ineligible patients with HCC who have liver-confined disease.

Treating Transplant-Ineligible Patients With HCC and Liver-Confined Disease

Focusing on liver-directed therapy, the panel provides clinical insights on the treatment of patients with hepatocellular carcinoma who have liver-confined disease and are not candidates for transplant.

Providing the interventional radiologist perspective, Harris Chengazi, MD, gives an overview of available treatment strategies.

Overview of Interventional Radiology Treatment Options

Radiation oncologists Nina Sanford, MD, and Jeffrey M. Ryckman, MD, provide an overview of treatment modalities, highlighting SRS, SBRT, and proton therapy.

The Basics of Radiation Oncology

Radiation oncologists Nina Sanford, MD, and Jeffrey M. Ryckman, MD, provide an overview of treatment modalities, highlighting SRS, SBRT, proton therapy, and how options have improved.

Tanios S. Bekaii-Saab, MD, discusses safety profile considerations for patients undergoing treatment for HCC, and the Oncology Brothers recap the discussion.

Treating HCC: Safety Profile Considerations

Tanios S. Bekaii-Saab, MD, discusses safety profile considerations for patients undergoing treatment for hepatocellular carcinoma, and the Oncology Brothers recap the entire discussion. 

Turning the focus to advanced-stage HCC, Tanios S. Bekaii-Saab, MD, offers comprehensive insights on first- and second-line treatment options.

First- and Second-Line Treatment of Advanced-Stage HCC

Medical oncologists outline localized therapy options for patients with early- and intermediate-stage hepatocellular carcinoma.

Localized Therapy in Early- and Intermediate-Stage HCC

Tanios S. Bekaii-Saab, MD, joins Rahul Gosain, MD, and Rohit Gosain, MD, to discuss treatment practices for early- and intermediate-stage HCC.

Treating Early- and Intermediate-Stage Hepatocellular Carcinoma

Tanios S. Bekaii-Saab, MD, joins Rahul Gosain, MD, and Rohit Gosain, MD, to discuss treatment practices for early- and intermediate-stage hepatocellular carcinoma.

Liver Cancer

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