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

Autor: Shaya J; Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.; Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA, USA., Kato S; Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA. smkato@ucsd.edu.; Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA, USA. smkato@ucsd.edu., Adashek JJ; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins Hospital, Baltimore, MD, USA. jadashek@westernu.edu., Patel H; Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA., Fanta PT; Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA., Botta GP; Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA., Sicklick JK; Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins Hospital, Baltimore, MD, USA.; Department of Surgery, Division of Surgical Oncology, University of California San Diego, UC San Diego Health, San Diego, CA, USA.; Department of Pharmacology, University of California San Diego, UC San Diego Health, San Diego, CA, USA., Kurzrock R; Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, USA.; WIN Consortium, Paris, France.; University of Nebraska, Lincoln, NE, USA.
Jazyk: angličtina
Zdroj: NPJ genomic medicine [NPJ Genom Med] 2023 Jan 20; Vol. 8 (1), pp. 1. Date of Electronic Publication: 2023 Jan 20.
DOI: 10.1038/s41525-022-00346-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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