Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer

Author(s): Shukui Qin, MD1; Jin Li, MD2; Yuxian Bai, MD, PhD3; Zishu Wang, MD4; Zhendong Chen, MD, PhD5; Ruihua Xu, MD, PhD6; Jianming Xu, MD7; Hongmei Zhang, MD8; Jia Chen, MD9; Ying Yuan, MD10; Tianshu Liu, MD11; Lin Yang, MD, PhD12; Haijun Zhong, MD13; Donghui Chen, MD14; Lin Shen, MD, PhD15; Chunyi Hao, MD, PhD15; Deliang Fu, MD, PhD16; Ying Cheng, MD17; Jianwei Yang, MD18; Qiong Wang, MD19; Baoli Qin, MD20; Hongming Pan, MD21; Jun Zhang, MD, PhD22; Xianhong Bai, MD23; and Qingshan Zheng, MD, PhD24
Source: DOI: 10.1200/JCO.22.02630 Journal of Clinical Oncology 41, no. 33 (November 20, 2023) 5163-5173.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Asian study of nimotuzumab (humanized EGFR-inhibitor) + gemcitabine (gem) vs. gem alone. The overall survival (OS) was 10.9 vs. 8.5 months in favor of the combination arm. While the OS difference is small, recall that the OS in the NALIRIFOX and FOLFIRINOX studies are similar. The safety profile of nimotuzumab + gemcitabine is superior to a triplet or double cytotoxic chemotherapy combination regimen. This drug is currently not available in the USA but is approved for nasopharyngeal carcinoma in China.


In a phase IIb trial of nimotuzumab plus gemcitabine, substantial clinical benefits were observed in patients with locally advanced or metastatic pancreatic cancer (PC). Therefore, we conducted a phase III clinical study to verify the efficacy and safety of this combination regimen in patients with K-Ras wild-type tumors ( identifier: NCT02395016).


Eligible patients were randomly assigned to receive nimotuzumab (400 mg once per week) or placebo followed by gemcitabine (1,000 mg/m2 on days 1, 8, and 15, once every 4 weeks) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) and the secondary end points were progression-free survival (PFS), response rates, and safety.


A total of 480 patients were screened; 92 patients were enrolled and 82 patients with K-Ras wild-type tumors were eligible. In the full analysis set, the median OS was 10.9 versus 8.5 months, while the restricted mean survival time (RMST) was 18.05 versus 11.14 months for the investigational versus control arm (ratio of control v investigation = 0.62 [0.40-0.97]; P = .036). Median PFS was 4.2 versus 3.6 months in the investigational versus control arm (log-rank P = .04; hazard ratio, 0.60 [0.37-0.99]) and the restricted mean PFS time was 8.08 versus 4.76 months (RMST ratio, 0.58 [0.38-0.90]; P = .036). Both OS and PFS were longer in the nimotuzumab group than in the placebo group. The objective response rates and disease control rates were 7% versus 10% and 68% versus 63% for the investigational and control groups, respectively. The incidence of adverse events were comparable between the two groups.


In patients with locally advanced or metastatic K-Ras wild-type PC, nimotuzumab plus gemcitabine significantly improved OS and PFS with a good safety profile.

Author Affiliations

1Cancer Center of Jinling Hospital, Nanjing, China; 2Shanghai East Hospital, Shanghai, China; 3Harbin Medical University Cancer Hospital, Harbin, China; 4The First Affiliated Hospital of Bengbu Medical College, Bengbu, China; 5The Second Hospital of Anhui Medical University, Hefei, China; 6Cancer Center of Sun Yat-sen University, Guangzhou, China; 7The Fifth Medical Center, General Hospital of People’s Liberation Army, Beijing, China; 8Xijing Hospital, Air Force Medical University of PLA, Xi’an, China; 9Jiangsu Cancer Hospital, Nanjing, China; 10The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; 11Zhongshan Hospital, Fudan University, Shanghai, China; 12National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 13Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China; 14The First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 15Peking University Cancer Hospital & Institute, Beijing, China; 16Huashan Hospital, Fudan University, Shanghai, China; 17Jilin Cancer Hospital, Changchun, China; 18Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China; 19Jiangyin People’s Hospital, Jiangyin, China; 20Liaoning Cancer Hospital & Institute, Shenyang, China; 21Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, China; 22Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 23Biotech Pharmaceutical Ltd, Corp, Beijing, China; 24Shanghai University of Traditional Chinese Medicine, Shanghai, China

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial

You may have enrolled a patient in this trial, but it seems we may have a new first line regimen. Surprisingly toxicity simar in both arms, but there was improvement in PFS and OS (17% reduction in death) although it wasn’t statistically significant in OS.
More diarrhea with nalirifox, but more neutropenia with gem abraxane.

Read More »

NAPOLI-3: A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

The NAPOLI-3 study assessed FOLFOX+ liposomal irinotecan vs. gemcitabine + nab-paclitaxel. NALIRIFOX was superior, with an OS of 11.1 vs. 9.2 months. Criticisms of modern gem trials are often that of rigid dosing requirements that differ from modern clinical practice. Additionally, it is unclear whether NALIRIFOX provides any meaningful benefit over FOLFIRINOX, and the cost is always a consideration.

Read More »