KRAS inhibition in pancreatic cancer: pooled efficacy and safety signals from early-phase studies
Tiede, K. O. M.; Teixeira, M. F.; De Moura, M.; Chiaini, O.; Sonbol, M. B.; Borad, M.; Bekaii-Saab, T.; Uson Junior, P. L. S.
Show abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, driven by KRAS mutations long deemed "undruggable". We conducted a meta-analysis of five early phase cohorts (n=301) that evaluated KRAS-targeted therapies in patients with PDAC. The pooled objective response rate was 28% (95% CI 22-35%), indicating promising activity in refractory PDAC, with consistent estimates across the studies (I2=0%). Gastrointestinal toxicities were common (diarrhea, 47%; nausea, 43%). These findings validate direct KRAS inhibition as a breakthrough concept in PDAC but are tempered by modest durability, risk of bias, and limitations of early phase designs, underscoring the need for biomarker-guided, rigorously designed clinical trials.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Feasibility of Administering Human Pancreatic Cancer Chemotherapy in a Spontaneous Pancreatic Cancer Mouse Model 92%
- Landscape of Clinical Trials in Cancer Cachexia: Assessment of Trends From 1995-2024 91%
- Study Protocol of A Phase II Study to Evaluate Safety and Efficacy of Neo-adjuvant Pembrolizumab and Radiotherapy in Localized Rectal Cancer 90%
Similar papers in this journal
- Clinical activity of MAPK targeted therapies in patients with non-V600 BRAF mutant tumors 92%
- Clinical activity of Mitogen-Activated Protein Kinase (MAPK) inhibitors in patients with MAP2K1 (MEK1)-mutated metastatic cancers 91%
- Cell-Free Tumor DNA Dominant Clone Allele Frequency (DCAF) Is Associated With Poor Outcomes In Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy 91%
Similar papers in this journal
- Resistance to the KRASG12D Inhibitor MRTX1133 is Associated with Increased Sensitivity to BET Inhibition 95%
- Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers 92%
- Immunomodulation of Pancreatic Cancer via Inhibition of SUMOylation and CD155/TIGIT Pathway 92%
Similar papers in this journal
- Phase 1b dose expansion and translational analyses of olaparib in combination with the oral AKT inhibitor capivasertib in recurrent endometrial, triple negative breast, and ovarian, primary peritoneal, or fallopian tube cancer 91%
- RRAS and RRAS2 mutations are recurrent oncogenic drivers in lung cancer and are sensitive to the pan-RAS inhibitor RMC-6236 89%
- Combination Therapies Targeting Alk-Aberrant Neuroblastoma In Preclinical Models. 89%
Similar papers in this journal
- Bacterial lipopolysaccharide as negative predictor of gemcitabine efficacy in advanced pancreatic cancer * translational results from the AIO-PK0104 phase 3 study 93%
- Spatial, Temporal, and Molecular Heterogeneity of ADC targets in High-Grade Serous Ovarian Carcinoma 89%
- An antibody-drug conjugate targeting GPR56 demonstrates efficacy in preclinical models of colorectal cancer 88%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.