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040			_aBMG
041			_aeng
100			_aO’Reilly, Eileen M. _eAutor _953775
245			_aDaraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer
300			_apáginas: 325-337
520			_aBackground: Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate–bound state of mutant and wild-type RAS. Methods: In this phase 3, international, open-label, randomized trial, we randomly assigned patients with previously treated mPDAC to receive daraxonrasib or chemotherapy of the investigator’s choice. The dual primary end points were overall survival and progression-free survival in the subpopulation of patients with RAS G12 mutations (the RAS G12 population). Key secondary end points included overall survival and progression-free survival in the overall population (which included patients with RAS G12, G13, or Q61 mutations or with no RAS mutation identified) and objective response and patient-reported quality of life in the RAS G12 and overall populations. Safety was also assessed. Results: A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group. Conclusions: Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy.
650			_aGASTROENTEROLOGÍA _912562
650			_aHEMATOLOGÍA _97422
650			_aONCOLOGÍA _912240
650			_aTRATAMIENTO EN ONCOLOGÍA _953713
650			_aCANCER DEL TRACTO GASTROINTESTINAL _953776
700			_aWainberg, Zev A. _953777
700			_aHendifar, Andrew E. _953778
700			_aBorad, Mitesh J. _953779
700			_aPietrantonio , Filippo _953780
700			_aPant, Shubham _953781
773	0		_022717 _922637 _dMassachusetts NEJM Group _oNEJM004 _tThe New England Journal of Medicine _wESSALUD _x0028-4793
942			_cARTICULOS _e2026-07-31 _zSQB
999			_c22744 _d22744