In the Chinese phase III NOTABLE trial reported in the Journal of Clinical Oncology, Shukui Qin, MD, and colleagues examined the addition of the EGFR inhibitor nimotuzumab to gemcitabine in patients with KRAS wild-type locally advanced or metastatic pancreatic cancer.
Study Details
In the multicenter, double-blind trail, 82 eligible patients enrolled between April 2015 and March 2021 were randomly assigned to receive intravenous nimotuzumab at 400 mg once weekly (n = 41) or placebo (n = 41) with gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 every 3 weeks followed by once weekly for 4 weeks. Treatment continued until disease progression or unacceptable toxicity.
The primary endpoint of the trial was overall survival. In addition to the hazard ratio as a measurement of the relative risk of an event, the restricted mean survival time ratio between groups was estimated after adjusting for covariates; a ratio of less than 1 indicated survival improvement in the investigational treatment group.
Shukui Qin, MD
Key Findings
Median overall survival was 10.9 months (95% confidence interval [CI] = 5.6–16.3 months) in the nimotuzumab group vs 8.5 months (95% CI = 5.7–10.0 months) in the control group (hazard ratio [HR] = 0.66, 95% CI = 0.42–1.05, P = .08). Restricted mean survival time was 18.05 months (95% CI = 11.71–24.38 months) in the nimotuzumab group vs 11.14 months (95% CI = 8.07–14.20 months) in the control group (restricted mean survival time [RMST] ratio = 0.62, 95% CI = 0.40–0.97, P = .036).
Median progression-free survival was 4.2 months (95% CI = 2.7–7.3 months) in the nimotuzumab group vs 3.6 months (95% CI = 2.0–5.0 months) in the control group (HR = 0.60, 95% CI = 0.37–0.99, P = .04). Restricted mean progression-free survival time was 8.08 months (95% CI = 5.20–10.94 months) in the nimotuzumab group vs 4.76 months (95% CI = 3.41–6.09 months) in the control group (RMST ratio = 0.58, 95% CI = 0.38–0.90, P = .036). Objective response rates were 7% vs 10%, and disease control rates were 68% vs 63%.
Adverse events of any grade occurred in 69% vs 65% of patients, most commonly hematologic adverse events in both groups. No grade ≥ 4 adverse events were observed. Serious adverse events occurred in 2% vs 4% of patients, and adverse events led to discontinuation of treatment in 4% vs 2%.
The investigators concluded, “In patients with locally advanced or metastatic KRAS wild-type pancreatic cancer, nimotuzumab plus gemcitabine significantly improved overall survival and progression-free survival with a good safety profile.”
Dr. Qin, of the Cancer Center of Nanjing Jinling Hospital, Nanjing University of Chinese Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Biotech Pharmaceutical Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.
