Adding Immunotherapy-Based Combo Boosts PFS in Unresectable Liver Cancer

CHICAGO — Combining standard transarterial chemoembolization (TACE) with the immunotherapy-based STRIDE regimen improved progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), the phase III EMERALD-3 study showed.

Median PFS was 13 months in patients who received a single dose of tremelimumab (Imjudo) and regular-interval durvalumab (Imfinzi), known as STRIDE, with lenvatinib (Lenvima) plus TACE versus 9.8 months for those who received TACE alone (HR 0.70, 95% CI 0.57-0.86, P=0.0007), reported Ghassan Abou-Alfa, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City.

While data on overall survival (OS) were immature, there was a positive trend in favor of the combination group, with a median OS of 39.5 months versus 34.7 months with TACE alone (HR 0.84, 95% CI 0.65-1.09, P=0.1814).

“EMERALD-3 is the first phase III clinical trial to demonstrate that a STRIDE-based regimen improves clinical outcomes when combined with TACE, supporting its role as a potential new treatment option for unresectable embolization-eligible HCC,” Abou-Alfa said here at the American Society of Clinical Oncology annual meeting.

However, patients who received STRIDE and TACE — with or without lenvatinib — experienced more side effects than those who received TACE alone, with grade 3 or 4 adverse events (AEs) reported in 71.4% of those who received STRIDE with lenvatinib and TACE, 64% of those who received STRIDE with TACE, and 28.6% of those who received TACE alone.

Serious AEs occurred in 64.1%, 50.9%, and 23.4% of patients in those three groups, respectively. Treatment discontinuation rates were 35.5% with STRIDE, lenvatinib, and TACE and 20.6% with STRIDE and TACE.

Considering the higher incidence of grade 3/4 adverse events and the discontinuation rates with the combination, invited discussant Stephen Chan, MBBS, MD, of the Chinese University of Hong Kong, asked whether it is “a worthwhile price to pay.”

“I think we need quality of life data,” he said. “We need data to see how our patients feel about this combination. This will help us make a decision whether the additional toxicity is a worthwhile price to pay for our patients.”

Abou-Alfa and colleagues also evaluated the 175 participants who received STRIDE and TACE without lenvatinib versus the first 175 participants who received TACE alone. Those who received STRIDE achieved a longer median PFS (12.9 vs 8.1 months; HR 0.71, 95% CI 0.56-0.91, P=0.0062) and OS (not calculable vs 32.9 months; HR 0.70, 95% CI 0.51-0.95, P=0.0233).

These results suggest “STRIDE as the driver of efficacy in the intent-to-treat population,” Abou-Alfa observed.

Chan also noted that the PFS benefit was similar in the STRIDE arms, no matter whether it was combined with lenvatinib.

“To me, considering the toxicity associated with STRIDE plus lenvatinib, it would make more sense that we don’t use lenvatinib from the beginning — just STRIDE plus TACE — and then consider lenvantinib as a subsequent treatment,” Chan added.

In explaining the rationale behind the study, Abou-Alfa pointed out that while TACE is commonly used all over the world for unresectable embolization-eligible HCC, it is associated with a PFS of only 8 to 10 months.

He noted that STRIDE has become a standard of care in advanced HCC after it demonstrated an OS benefit compared with sorafenib (Nexavar) in the HIMALAYA trial. Thus, he and his team hypothesized that TACE combined with STRIDE and lenvatinib could further enhance antitumor activity.

The open-label EMERALD-3 trial included 760 patients treated at 171 centers across 22 countries in North America, Europe, South America, and Asia.

Patients were randomized 1:1:1 to a single priming dose of tremelimumab 300 mg plus durvalumab 1,500 mg on day 1 and then every 4 weeks plus TACE and lenvatinib; STRIDE plus TACE; or TACE alone, until each arm reached 175 participants, with randomization continuing in the first and third arms until each reached approximately 275 participants.

Median age was 67 years in the group receiving the STRIDE regimen plus TACE and lenvatinib, and 65 years in the other two groups, and the majority were Asian. Most patients had an Eastern Cooperative Oncology Group performance status of 0, 45-57% had hepatitis B virus, and 11-13% had hepatitis C virus.

The most common grade 3 or 4 AEs with the STRIDE regimen included hypertension, post-embolization syndrome, increases in aspartate aminotransferase and lipase, hypokalemia, and anemia.

Please enable JavaScript to view the comments powered by Disqus.