The CheckMate 9DW trial, led by Dr. Masatoshi Kudo and his esteemed colleagues, presents an important advancement in the treatment of unresectable hepatocellular carcinoma (HCC). This study compares the efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) against lenvatinib (LEN) or sorafenib (SOR) as first-line therapies. Published at the ASCO Gastrointestinal Cancers Symposium, this global phase 3, randomized, open-label study highlights the potential of immunotherapy in providing a survival advantage over existing tyrosine kinase inhibitors.Study Design and Key Characteristics
The study enrolled 668 patients with unresectable HCC who had not previously received systemic therapy. Eligibility criteria required at least one measurable lesion, a Child-Pugh score of 5 or 6, an ECOG performance status of 0 or 1, and no main portal vein invasion. Patients were randomized to receive either NIVO combined with IPI or the investigator’s choice of LEN or SOR. Stratification factors included etiology (HBV, HCV, or uninfected) and alpha-fetoprotein (AFP) levels below or above 400 ng/mL.
The median age was around 65 years, with a male predominance. The etiology of HCC varied, with HBV, HCV, and uninfected cases across both treatment arms. Baseline characteristics were well-balanced, ensuring comparability of outcomes.
Efficacy Outcomes
NIVO + IPI provided a statistically significant improvement in overall survival (OS) compared to LEN/SOR. The median OS was 23.7 months for NIVO + IPI versus 20.6 months for LEN/SOR, with a hazard ratio (HR) of 0.79 (95% CI, 0.65-0.96; p = 0.018). The OS benefit was highlighted by higher survival rates at 24 and 36 months, with the NIVO + IPI group achieving 49% and 38% respectively, compared to 39% and 24% in the LEN/SOR group.
NIVO + IPI showed a notable improvement in overall response rate (ORR), achieving 36% compared to 13% for LEN/SOR. The complete response (CR) rate was 7% in the NIVO + IPI group versus 2% in the LEN/SOR group. The median duration of response (DOR) favored NIVO + IPI at 30.4 months compared to 12.9 months for LEN/SOR.
Subgroup Analysis
The ORR was consistently higher with NIVO + IPI across subgroups including age, sex, geographic regions, ECOG performance status, and etiological factors. For example, patients with ECOG 0 had an ORR of 39.5% with NIVO + IPI compared to 12.3% with LEN/SOR. Patients with macrovascular invasion showed ORRs of 38% and 13.4% respectively, favoring NIVO + IPI.
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