Nimotuzumab Plus Chemotherapy Extends OS in KRAS Wild-Type Advanced Pancreatic Cancer

In the phase 3 NOTABLE trial (NCT02395016), the addition of nimotuzumab to gemcitabine lead to an improvement in overall survival (OS) compared with gemcitabine alone in patients with KRAS wild-type advanced pancreatic cancer, according to results presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

In particular, the combination improved OS among those who did not need surgery for obstruction of a pancreatic bile duct.

“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, professor and chief physician of the Cancer Center, Jinling Hospital, Nanjing University of Chinese Medicine, said in a press release.² “The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer.”

In the prospective, double-blind study, median OS in patients treated with nimotuzumab plus gemcitabine was significantly longer when compared with those who received gemcitabine plus a placebo at 10.9 months vs 8.5 months, respectively (HR, 0.50; 95% CI, 0.06-0.94; P = .025). Moreover, the combination regimen demonstrated 1- and 3-year OS rates of 43.6% and 13.9%, respectively, compared with 26.8% and 2.7% with the placebo regimen.

Among those who did not need surgery to remove a biliary obstruction, median OS was 11.9 months and 8.5 months with the combination versus the placebo regimens, respectively (HR, 0.54; 95% CI, 0.33-0.88; P = .037). Similarly, OS was improved for those who had no surgical history and received treatment with nimotuzumab plus gemcitabine at 15.8 months compared with placebo and gemcitabine at 6.0 months (HR, 0.40; 95% CI, 0.19-0.84).

Median progression-free survival (PFS) was also improved with nimotuzumab plus gemcitabine at 4.2 months vs gemcitabine alone at 3.6 months (HR, 0.56; 95% CI, 0.12-0.99; P = .013). For those with no surgical history of biliary obstructions, median PFS was 5.5 months vs 3.4 months in the nimotuzumab and placebo groups, respectively (P = .008).

The incidence of adverse events (AEs) was similar among both groups. The most common AEs with the anti-epidermal growth factor receptor monoclonal antibody were neutropenia (11.1%), leukopenia (8.9%), and thrombocytopenia (6.7%)

The phase 3 trial evaluated the efficacy and safety of nimotuzumab in combination with gemcitabine versus gemcitabine alone in patients with KRAS wild-type locally advanced or metastatic pancreatic cancer. In addition, subgroup analyses were conducted based on the need for surgery to remove bile duct obstructions prior to receiving chemotherapy, as those who do not need surgery to repair obstructions typically have better liver function and no jaundice, indicating a potential advantage for tolerating chemotherapy, according to the release.

In total, 92 patients in China were randomized to receive either 400 mg nimotuzumab every week followed by 1000 mg/m² gemcitabine on days 1, 8, and 15 of every 28-day cycle or placebo plus gemcitabine until progression or unacceptable toxicity.

OS served as the primary end point, while secondary end points included PFS, objective response rate (ORR), and safety.

“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” ASCO expert in gastrointestinal (GI) cancers Cathy Eng, MD, FACP, FASCO, David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, professor of medicine (hematology and oncology), co-director of GI oncology, vice-chair of the SWOG GI Committee, and director of the Vanderbilt-Ingram Cancer Center Young Adult Cancers Initiative, said in a press release.²

“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 pancreatic cancer patients,” she added. “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.”

_References

_{1. Qin S, Bai Y, Wang Z, et al. Nimotuzumab combined with gemcitabine versus gemcitabine in KRAS wild‐type locally advanced or metastatic pancreatic cancer: A prospective, randomized‐controlled, double‐blinded, multicenter, and phase III clinical trial. J Clin Oncol. 2022;40(suppl 17):LBA4011. doi:10.1200/JCO.2022.40.17_suppl.LBA4011}

_{2. Nimotuzumab Significantly Improves Overall Survival for K-Ras Wild-Type Advanced Pancreatic Cancer. News release. American Society of Clinical Oncology. June 3, 2022. Accessed June 3, 2022. https://bit.ly/3x4hRve}