The addition of nimotuzumab, an EGFR-targeting monoclonal antibody, to gemcitabine increased overall survival in patients with KRAS wild-type advanced pancreatic cancer, particularly those who did not need surgery for obstruction of a pancreatic bile duct, according to data from the phase III NOTABLE clinical trial presented by Qin et al at the 2022 ASCO Annual Meeting (Abstract LBA4011).

“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer. The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” said co–lead author Shukui Qin, MD, Professor and Chief Physician of the Cancer Center, Jinling Hospital, Nanjing University of Chinese Medicine. Dr. Qin’s co–lead author is Jin Li, MD, Professor and Director of the Oncology Department at the East Hospital of Shanghai Tongji University, China.

Study Background

An estimated 62,210 people in the United States will be diagnosed with pancreatic cancer this year. When diagnosed at an advanced stage, current therapies provide a median overall survival benefit of approximately 6 to 8 months.

Pancreatic cancer rates in China are increasing; cases in China account for about 25.2% (124,994 new cases in 2020) of all newly diagnosed cancers and about 26.1% (121,853 deaths in 2020) of deaths from pancreatic cancer worldwide. Mutations in the KRAS gene account for 85% to 90% of all pancreatic cancers; 10% to15% of pancreatic cancers are KRAS wild type.

Nimotuzumab, developed as a joint Chinese-Cuban venture, was approved by the Chinese National Medical Products Administration to be marketed in China in 2008 for the treatment of nasopharyngeal carcinoma. A series of clinical studies of nimotuzumab for head and neck, cervical, esophageal, and other cancers are ongoing in China. The drug has not been approved by the U.S. Food and Drug Administration.

NOTABLE Methodology

In the prospective double-blind phase III NOTABLE clinical trial, patients in China with locally advanced or metastatic pancreatic cancer were randomly assigned to receive either nimotuzumab followed by gemcitabine or placebo plus gemcitabine until disease progression or unacceptable toxicity. The researchers conducted subgroup analyses based on whether the patients needed surgery to remove bile duct obstructions prior to receiving chemotherapy. Patients without the need for surgery to repair obstructions have better liver function and no jaundice, and may therefore better tolerate chemotherapy.

The primary endpoint was overall survival; secondary endpoints included progression-free survival, objective response rate, and safety.

Key Findings

Median overall survival was longer for patients in the nimotuzumab/gemcitabine group (10.9 months) compared to those who received gemcitabine plus placebo (8.5 months). The 1-year overall survival rate was 43.6% in the nimotuzumab/gemcitabine group vs 26.8% in the placebo/gemcitabine group; 3-year rates were 13.9% vs. 2.7%, respectively. The median progression-free survival was 4.2 months in the nimotuzumab/gemcitabine group vs 3.6 months in the placebo/gemcitabine group.

The overall survival benefit in patients who did not need surgery to remove a biliary obstruction was 11.9 vs 8.5 months. For those who had no surgical history, it was 15.8 vs 6.0 months for the nimotuzumab/gemcitabine vs placebo/gemcitabine groups, respectively. Progression-free survival for those who had no surgical history for a biliary obstruction was 5.5 vs 3.4 months in the nimotuzumab/gemcitabine vs placebo/gemcitabine groups, respectively.

The incidence of adverse events in the nimotuzumab/gemcitabine group was similar to the placebo/gemcitabine group. The most common adverse events for those who received nimotuzumab/gemcitabine were neutropenia (11.1%), leukopenia (8.9%), and thrombocytopenia (6.7%).

Next Steps

The patients in the study continue to be followed up with for overall survival and long-term safety endpoints. The investigators continue to recruit patients in order to enroll a population that is as representative of the real-world population of patients with pancreatic cancer as possible.

ASCO Perspective

Cathy Eng, MD, FACP, FASCO

“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest. The investigators have evaluated a subset of pancreatic cancer, KRAS wild-type, which is rarely investigated prospectively because this form of the cancer represents less than 10% of all patients with pancreatic cancer. Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest. We should consider validating any potential advances to make a true difference in the lives of all patients with pancreatic cancer,” said Cathy Eng, MD, FACP, FASCO, ASCO Expert in gastrointestinal cancers.

Disclosure: This trial was conducted in China and sponsored by Biotech Pharmaceutical Corp. Ltd. For full disclosures of the study authors, visit coi.asco.org.