Jonathan S. Zager, MD, Reviews Percutaneous Hepatic Perfusion With Melphalan in Ocular Melanoma With Hepatic Metastases

At ASCO 2022, Jonathan S. Zager, MD, spoke about the phase 3 FOCUS trial which analyzed patients with hepatic-dominant ocular melanoma receiving percutaneous hepatic perfusion with melphalan or best alternative care.

Results from the phase 3 FOCUS trial (NCT02678572) that read out at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting showed that patients with hepatic-dominant ocular melanoma who received percutaneous hepatic perfusion (PHP) with melphalan had superior outcomes vs best alternative care (BAC), indicating a promising treatment strategy for this rare indication.

In the trial, patients were randomized 1:1 to PHP or BAC, the latter of which could include transarterial chemoembolization, pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine. The primary end point of objective response rate was 36.3% (95% CI, 26.44%-47.01%) vs 12.5% (95% CI, 3.51%-28.99%) in those receiving PHP or BAC, respectively, and a median duration of response was 14 months (95% CI, 8.31-17.74) vs not calculable (NC; 95% CI, 6.93-NC). Median PFS with PHP and BAC was 9.03 months (95% CI, 6.34-11.56) vs 3.12 month (95% CI, 2.89-5.65), respectively (P = .0003); corresponding median OS was 19.25 months (95% CI, 16.72-24.35) vs 14.49 (95% CI, 11.10-19.78).

“It was a successful trial that doubled the response rate, tripled progression-free survival in terms of months, and showed that this treatment makes a difference,” Jonathan S. Zager, MD, chief academic officer in the departments of Cutaneous Oncology and Sarcoma at Moffitt Cancer Center and chair in the department of Oncologic Sciences at the University of Southern Florida, said in an interview with CancerNetwork®.

Zager further discussed the results of the trial and some of the key takeaways. Additionally, he looked ahead to future research and the potential for an FDA submission.

CancerNetwork®: What was the rationale for the phase 3 FOCUS trial?

Zager: The FOCUS trial initially started out as a randomized trial looking at percutaneous hepatic perfusion vs best alternative care for patients who have hepatic-dominant or hepatic-only ocular melanoma metastases. The purpose of the trial was to select this group of patients for which we have little systemic therapy options. Ocular melanoma tends to spread to the liver if it’s going to metastasize, and that’s usually the cause of death. The purpose of this trial was to look at whether we can isolate the liver, perfuse it with high-dose chemotherapy, and help these patients.

What were the results of the trial and how did it compare with the standard of care?

The trial initially was a randomized trial of percutaneous hepatic perfusion vs best alternative care. Four [regimens were included for the] best alternative care arm which was chemotherapy embolization, pembrolizumab, ipilimumab, or dacarbazine, and it was a 1:1 randomization. At some point, we realized that patients who were randomized to the best alternative care arm were refusing their treatment and/or flying off to Europe where this is approved. We talked to the FDA and we made it a single-arm trial from the midpoint onwards. When it was a randomized trial, we have shown that percutaneous hepatic perfusion triples progression-free survival vs best alternative care.

Looking at the safety profile, did anything surprise you?

The safety profile [consists of] mostly hematologic toxicity. [Filtering] out the chemotherapy extracorporeally, outside the patient’s body, isn’t 100% efficient. We know that some chemotherapy will leak back into the patient’s body and it usually causes some bone marrow toxicity. The overwhelming majority of those patients are either treated with observation, growth factors, or other blood products as an outpatient, but it doesn’t usually stop them from getting [subsequent] percutaneous hepatic perfusion at 6-to-8-week intervals. The toxicities do not preclude them from continuing the trial in the vast majority of patients.

How will future research impact the treatment paradigm for this patient population?

My goal is to help the company bring it to the FDA in the latter half of this year or early next year and have this approved. If this is approved, there will be strong evidence supporting treatment for patients who have very few options. It’s extremely well tolerated. Most of my patients go home day 1 after their procedure. We do the procedure, they stay overnight, they go home the next day, and they go on to get 5 or 6 of these [treatments] in the span of about 36 to 48 weeks. The efficacy has been shown to be positive in terms of the best alternatives out there.

Right now, we currently have an expanded access protocol while we’re waiting for the FDA submission, and I have 4 patients already signed up to get their PHPs in the next 2 weeks on that protocol. I’m sure there’ll be more research efforts looking at different agents and different filter combinations for different histologic types down the road. There are investigator-initiated trials worldwide looking at this [strategy and] combining it with checkpoint inhibitor therapy, or percutaneous hepatic perfusion sandwiched between checkpoint inhibitors or checkpoint inhibitors sandwiched between percutaneous hepatic perfusion.

What should your colleagues take away from the presentation?

It’s an efficacious treatment on a patient population that had very few options. There is some toxicity, but it’s completely manageable and the vast majority [of patients can be] managed as an outpatient. It’s a very powerful treatment for a patient population that had few options and traditionally had poor survival.


Zager JS, Orloff MM, Ferrucci PF, et al. FOCUS phase 3 trial results: Percutaneous hepatic perfusion (PHP) with melphalan for patients with ocular melanoma liver metastases (PHP-OCM-301/301A). J Clin Oncol. 2022;40(suppl 16):9510. doi:10.1200/JCO.2022.40.16_suppl.9510