Novel treatment option for KRAS wildtype pancreatic cancer 

Gemcitabine plus nimotuzumab demonstrated overall survival (OS) benefits over gemcitabine alone for patients with KRAS wildtype metastatic pancreatic ductal adenocarcinoma (mPDAC) or locally advanced pancreatic cancer (LAPC). The results of the phase 3 Notable trial show the value of determining KRAS status in pancreatic cancer. 

Activation of the epidermal growth factor receptor (EGFR)-Ras-Raf-MEK-ERK pathway plays a part in patients with KRAS wildtype pancreatic cancer [1]. Therefore, the phase 3 NOTABLE trial (NCT02395016) randomised patients with KRAS wildtype locally advanced or metastatic pancreatic cancer to gemcitabine and placebo (n=41) or gemcitabine plus nimotuzumab (n=41), which is an EGFR-targeting monoclonal antibody. OS was the primary endpoint of this study. Prof. Shukui Qin (Cancer Center of Jinling Hospital, China) presented the results [2].

The combination therapy arm outperformed the placebo arm significantly for OS (10.9 vs 8.5 months; HR 0.50; P=0.024), decreasing the risk of mortality by 50%. In addition, the 1-year and 3-year OS rates were 43.6% and 13.9% for patients treated with nimotuzumab and 26.8% and 2.7% for patients who received placebo.

Importantly, the combination therapy was well tolerated and no substantial increase in grade 3 adverse events was observed among patients who received nimotuzumab. The most frequently reported adverse events in the nimotuzumab arm were neutropenia (11.1%), leukopenia (8.9%), and thrombocytopenia (6.7%). Prof. Qin added that the OS curves of the 2 treatment arms separated rather late, suggesting there might be subgroups within the KRAS wildtype subgroup of tumours that behave differently in response to nimotuzumab.

This trial demonstrated that it is worth determining KRAS status in pancreatic cancer. Gemcitabine plus nimotuzumab displayed itself as a novel option for patients with KRAS wildtype mPDAC/LAPC who otherwise would have received only gemcitabine. ”It would be interesting to see how combination chemotherapy would behave in the KRAS wildtype mPDAC population,” concluded Thomas Seufferlein (Ulm University Hospital, Germany), discussant of this session [3].

1. Luchini C, et al. J Exp Clin Cancer Res. 2020;39(1):227.
2. Qin S, 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. LBA4011, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.
3. Seufferlein T, et al. Is it worth determining KRAS Status in Pancreas Cancer? Discussant LBA 4011, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August 202217 May 2024