Adding nimotuzumab to treatment with gemcitabine improves survival outcomes in patients with KRAS wild-type advanced pancreatic cancer, according to trial results published in the Journal of Clinical Oncology.
In this phase 3 trial, the addition of nimotuzumab prolonged progression-free survival (PFS) and overall survival (OS) but did not significantly increase toxicity.
This trial (ClinicalTrials.gov Identifier: NCT02395016) was conducted in China. It included 82 evaluable patients with KRAS wild-type, locally advanced or metastatic pancreatic cancer. The patients’ median age was 55 years (range, 19-73), 62% were men, 79% had metastatic disease, and 50% had more than 3 metastatic sites. Patients had undergone surgery (56%), adjuvant chemotherapy (7%), radiation (2%), and biliary obstruction treatment (10%).
The patients were randomly assigned to receive nimotuzumab (n=41) or placebo (n=41), each in combination with gemcitabine. Baseline characteristics were well balanced between the arms. Patients were treated until disease progression or unacceptable toxicity.
The median OS was 10.9 months in the nimotuzumab-gemcitabine arm and 8.5 months in the gemcitabine-alone arm (Cox proportional hazard ratio [HR], 0.66; 95% CI, 0.42-1.05; P =.08).
The researchers noted that, once the trial was completed, the survival curves overlapped until 6 months and then gradually separated, so “the proportional hazard assumption for the Cox regression model does not hold.” The researchers therefore used the restricted mean survival time (RMST) model to calculate survival differences.
The RMST was 18.05 months in the nimotuzumab arm and 11.14 months in the gemcitabine-alone arm (RMST ratio of control vs treatment, 0.62; 95% CI, 0.40-0.97; P =.036).
The median PFS was 4.2 months in the nimotuzumab arm and 3.6 months in the gemcitabine-alone arm (HR, 0.60; 95% CI, 0.37-0.99; P =.04). The restricted mean PFS time was 8.08 months in the nimotuzumab arm and 4.76 months in the gemcitabine-alone arm (RMST ratio, 0.58; 95% CI, 0.38-0.90 P =.036).
The rate of adverse drug reactions (ADRs) was similar between the arms — 69% in the nimotuzumab arm and 65% in the gemcitabine-alone arm. The rate of serious ADRs was 2% and 4%, respectively. The rate of dose reduction or discontinuation was 9% and 13%, respectively.
The most common hematologic adverse events (in the nimotuzumab arm and gemcitabine-alone arm, respectively) were neutropenia (27% vs 24%), thrombocytopenia (22% vs 20%), and leukopenia (27% in both arms). The most common non-hematologic adverse event was fatigue (4% in the nimotuzumab arm and 13% in the gemcitabine-alone arm).
The researchers noted that this study is limited by a lack of data on EGFR expression, lack of information on subsequent treatments after disease progression, and the use of gemcitabine as a comparator rather than gemcitabine/nab-paclitaxel or combination leucovorin, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX). Nevertheless, the results suggest that adding nimotuzumab to gemcitabine can improve PFS and OS in patients with KRAS wild-type advanced pancreatic cancer.
“This randomized trial confirms that identification of KRAS wild-type PC [pancreatic cancer] is clinically important and therapeutically relevant and can be successfully targeted,” Eileen M. O’Reilly, MD, an associate editor for the Journal of Clinical Oncology, wrote in a comment on the results.
Disclosures: This research was supported by Biotech Pharmaceutical Co, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Qin S, Li J, Bai Y, et al. Nimotuzumab plus gemcitabine for K-RAS wild-type locally advanced or metastatic pancreatic cancer. J Clin Oncol. Published online August 30, 2023. doi:10.1200/JCO.22.02630