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.

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.

PURPOSE

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 (ClinicalTrials.gov identifier: NCT02395016).

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSION

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

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