Efficacy and Safety of KRAS-Targeted Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma
Faiza Fatima, Muhammad A. Javed, Aeliya Mirza, Shahzaib Ahmad, Zara Shahzad, Ali MuradObjectives:
Kirsten rat sarcoma viral oncogene homolog mutations drive over 90% of pancreatic ductal adenocarcinoma (PDAC). Direct RAS inhibitors have shown early activity, but the only prior meta-analysis pooled early-phase monotherapy cohorts and predates the first phase 3 randomized trial and newer combination regimens. We estimated the objective response rate (ORR), disease control rate (DCR), and safety of Kirsten rat sarcoma viral oncogene homolog-targeted therapy in locally advanced or metastatic PDAC.
Methods:
PubMed/MEDLINE, Embase, and SCOPUS were searched from inception through July 2026. Single-arm proportions were pooled using a random-effects generalized linear mixed model; RASolute 302 was analyzed separately. Prespecified subgroups stratified ORR by mechanistic class and line of therapy.
Results:
A total of 1008 patients from 16 cohorts across 7 trials were included; 15 single-arm cohorts (507 patients) contributed to pooled estimates. Pooled ORR was 38.9% (95% CI: 29.9%-48.8%;
Conclusions:
Kirsten rat sarcoma viral oncogene homolog-directed therapy produces meaningful antitumor activity in previously treated PDAC, greatest for combination regimens and earlier treatment; the evidence remains heterogeneous and largely early-phase, and randomized trials are needed before routine adoption.