ASCO26: AZ triplet makes waves in frontline liver cancer
A three-drug regimen incorporating AstraZeneca's immune checkpoint inhibitors Imfinzi and Imjudo has reduced the risk of disease progression or death by 30% when used as a first-line therapy for a common form of liver cancer.
The EMERALD-3 trial looked at a regimen of PD-L1 inhibitor Imfinzi (durvalumab) and CTLA4 inhibitor Imjudo (tremelimumab) – given with or without Eisai's multikinase inhibitor Lenvima (lenvatinib) – on top of a procedure known as transarterial chemoembolisation (TACE) to patients with hepatocellular carcinoma that could not be removed with surgery.
TACE is a minimally invasive treatment for liver cancer that combines chemotherapy and vascular blockage, designed to cut off the oxygen and nutrient supply to tumours, which is the standard therapy for patients in this setting.
It's not that effective, however, with a median progression-free survival (PFS) of only eight to 10 months, and repeated administrations get less effective and can damage the liver. At the moment, there are no FDA-approved systemic therapies for these patients, although, salvage therapy with off-label targeted drugs or other immunotherapies is often used.
When the Imfinzi/Imjudo/Lenvima triplet therapy was added, median PFS was extended to 13 months, compared to 9.8 months with TACE alone, and there was also a trend towards improved overall survival (OS), which came in at 39.5 months and 34.7 months, respectively.
Lead investigator Ghassan Abou-Alfa of Memorial Sloan Kettering Cancer Center, who presented the results at ASCO, said the findings suggest the regimen "may reduce the need for repeated TACE procedures, delay the time until additional treatment is needed, preserve liver function, and prolong survival."
Improvements over TACE on its own were also seen with Imfinzi and Imjudo dual therapy, given in a regimen known as STRIDE – standing for Single Tremelimumab Regular Interval Durvalumab – with a median PFS of 12.9 months versus 8.1 months for TACE alone, which was a 29% improvement, and a two-year OS rate of 68% versus 57.8%.
That raises the interesting notion that STRIDE could be contributing the bulk of the benefit, which will be monitored as the trial progresses. However, the OS data has been complicated by more patients in the control group going on to receive salvage therapy after TACE failure.
The potential for dual therapy is also of note, given that there is a trade-off in toxicity, with grade 3-4 adverse events seen in 62.7% of STRIDE plus Lenvima patients, 48.6% of the STRIDE group, and 18.6% among those getting TACE alone.
The PFS improvements make both the triplet and doublet regimens "a compelling therapeutic option" for unresectable HCC patients treated with TACE, said ASCO commentator Vishwanath Sathyanarayanan of Apollo Hospitals in Bangalore, India.
"These findings are likely to influence clinical practice and may be considered practice-changing," he added.
Imfinzi is already approved by the FDA for use in combination with Imjudo for unresectable, advanced HCC, and AZ has said it intends to share the EMERALD-3 data with regulators.
Another study, EMERALD-2, is looking at Imfinzi with or without bevacizumab as adjuvant therapy for HCC patients who are at high risk of recurrence after successful curative surgery or ablation techniques and is due to complete later this year.
