Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis

Authors

• Justin Shaya, University of California San Diego Moores Cancer Center
• Shumei Kato, University of California San Diego Moores Cancer Center
• Jacob J. Adashek, University of California San Diego Moores Cancer Center
• Hitendra Patel, University of California San Diego Moores Cancer Center
• Paul T. Fanta, University of California San Diego Moores Cancer Center
• Gregory P. Botta, University of California San Diego Moores Cancer Center
• Jason K. Sicklick, University of California San Diego Moores Cancer Center, The Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins Hospital, University of California San Diego,
• Razelle Kurzrock, Medical College of Wisconsin, WIN Consortium, University of Nebraska-Lincoln

Document Type

Article

Date of this Version

1-20-2023

Citation

npj Genomic Medicine (2023) 8:1 ; https://doi.org/10.1038/s41525-022-00346-5

Comments

Open access.

Abstract

Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/ patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = 0.008). No grade 3–4 toxicities occurred. The longest responder achieved partial remission (17.5 months) by co-targeting MEK and CDK4/6 alterations (chemotherapy-free). Therefore, genomically matched targeted agent combinations were active in these advanced pancreatic cancers. Larger prospective trials are warranted.