Two late-breaking presentations at this year’s ASCO GI Cancers Symposium provided potentially practice-changing data on the addition of immunotherapy to standard-of-care (SOC) treatments for hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC) with unmet needs.
Riccardo Lencioni, MD, presented the initial results of EMERALD-1, a phase 3, randomized, placebo-controlled study of transarterial chemoembolization (TACE) combined with durvalumab (D) ± bevacizumab (B) in patients with unresectable HCC eligible for embolization. Although TACE has been a SOC for these patients for over 20 years, the median progression-free survival (PFS) remains around seven to eight months. Patients were randomly assigned to D+TACE followed by D (n=207), D+TACE followed by D+B (n=204), or placebo+TACE followed by placebo (P; n=205). All received 1-4 TACE procedures within 16 weeks.
After two years of follow-up, median PFS was statistically significantly improved with D+B+TACE at 15.0 months versus 8.2 months for placebo (HR 0.77, 95% CI 0.61-0.98; P=.032), meeting the primary endpoint. Median PFS, a secondary endpoint, for D+TACE was 10.0 months, not significantly different from that for P+TACE (P=.683.
D+B+TACE improved median time to progression versus D+TACE or P+TACE (22.0 versus 11.5 versus 10.0 months, respectively); the overall response rates were 43.6% versus 41.0% versus 29.6%, respectively. Safety profiles were consistent with the known adverse events of D, B, and TACE. No deaths occurred with D+B+TACE.
Dr. Lencioni said D+B+TACE is a potential new SOC in unresectable HCC eligible for embolization. Discussant Josep M. Llovet, MD, PhD, agreed. He called this study well-designed, noting it is the first phase 3 randomized controlled trial in 20 years to yield positive PFS results. EMERALD-1 is ongoing, as are other immunotherapy trials with TACE or transarterial radioembolization (TARE).
Thierry Andre, MD, presented the first results from a prespecified interim analysis of CheckMate 8HW, a randomized, phase 3 study comparing the checkpoint inhibitors nivolumab plus ipilimumab to nivolumab or chemotherapy in patients with high-level microsatellite instability or deficient mismatch repair (MSI-H/dMMR) mCRC. Previously, outcomes in response to standard chemotherapy with and without targeted therapies in this setting have been poor.
Results were reported for patients randomly assigned to nivolumab+ipilimumab (n=202) or to the investigator's choice of chemotherapy (n=101) as first-line treatment.
At a median follow-up of 24. 3 months, median PFS, one of the two primary endpoints, was met median PFS was not reached in the nivolumab+ipilimumab arm vs a median PFS of 5.9 months with chemotherapy (HR 0.21, 95% CI 0.13-0.35; P<.0001). The 24-month PFS rates were 72% vs 14%, respectively. The PFS benefit of the dual immunotherapy combination was seen across all subgroups, including those with KRAS or NRAS mutations or baseline liver, lung, or peritoneal metastases.
No new safety signals for the nivolumab+ipilimumab combination were identified. There were two deaths in this group, one from myocarditis related to crossover treatment.
Dr. Andre said results support nivolumab+ipilimumab as a SOC first-line treatment option for patients with MSI-H/dMMR mCRC. CheckMate 8HW is ongoing to assess the other primary endpoint of PFS for nivolumab+ipilimumab versus nivolumab across all lines of therapy.
Dr. Lederman has no conflicts of interest to report.
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