麻豆传媒

CHICAGO -- Adding an EGFR inhibitor to chemotherapy significantly improved overall survival (OS) in advanced KRAS wild-type pancreatic cancer, a randomized trial showed.

Median OS improved from 8.5 months with gemcitabine alone to 10.9 months with the addition of nimotuzumab. One-year survival almost doubled among patients who received the monoclonal antibody, and more than four times as many patients in the nimotuzumab group were alive at 3 years, reported Shukui Qin, MD, of Nanjing University of Chinese Medicine in China, here at the American Society of Clinical Oncology (ASCO) annual meeting.

"We believe our trial will be a breakthrough in the field of pancreatic cancer," Qin said in a statement. "The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer."

The best results occurred in patients who did not require surgery for biliary obstruction and those who had no history of surgery.

Because of the rarity of KRAS wild-type pancreatic cancer (~10% of all pancreatic cancer), few studies have prospectively evaluated new treatment strategies, said Cathy Eng, MD, of Vanderbilt University Medical Center in Nashville.

"Additional studies in comparison with the combination of gemcitabine and nab-paclitaxel would be of interest," said Eng, an ASCO expert in gastrointestinal cancers. "We should consider validating any potential advances to make a true difference in the lives of all patients with pancreatic cancer."

ASCO chief medical officer Julie Gralow, MD, had a more circumspect reaction to the findings.

"It's a small trial of 92 patients; it was an entirely Chinese population; it's the KRAS subtype of pancreatic cancer, and we're investigating a lot of other agents in this population," she told 麻豆传媒. "This will not change practice. We will not have access to this drug. It might encourage us to study other anti-EGFR antibodies in this setting. It's an interesting kind of a proof-of-principle trial."

Advanced pancreatic cancer has a poor prognosis, with a median OS of 6 to 8 months with currently available therapies. Chemotherapy remains the mainstay of treatment, particularly gemcitabine.

Investigators in the all-Chinese NOTABLE trial enrolled patients with locally advanced or metastatic pancreatic cancer with confirmed KRAS wild-type status. Patients were randomized to gemcitabine plus placebo or nimotuzumab. Treatment continued until disease progression or unacceptable toxicity, and the primary endpoint was OS.

The results showed that adding the anti-EGFR antibody to chemotherapy led to statistically significant improvement in median OS (HR 0.50, 95% CI 0.06-0.94, P=0.025). The 1-year OS rate was 43.6% in the nimotuzumab arm versus 26.8% in the placebo group. Three-year OS was 13.9% with nimotuzumab and 2.7% with placebo.

In the subgroup of patients who did not need surgery for biliary obstruction, median OS with nimotuzumab increased to 11.9 months versus 8.4 months in the placebo group (HR 0.54, 95% CI 0.33-0.88, P=0.037). Patients with no surgical history had a median OS of 15.8 months with nimotuzumab versus 6.0 months with placebo (HR 0.40, 95% CI 0.19-0.84).

The addition of nimotuzumab led to a small but statistically significant improvement in median progression-free survival (PFS, 4.2 vs 3.6 months, HR 0.56, 95% CI 0.12-0.99, P=0.013). PFS improved to 5.5 months with nimotuzumab versus 3.4 months with placebo in patients who did not require surgery for biliary obstruction (P=0.008).

The most common grade 3 treatment-related adverse events (TRAEs) associated with nimotuzumab were neutropenia (11.1%), leukopenia (8.9%), and thrombocytopenia (6.7%). No patient in either arm developed grade 4 TRAEs.

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