000			03071nam a2200325 4500
001			ESSALUD
005			20260903144909.0
007			ta
008			t pe ||||| |||| 00| 0 spa d
040			_aBMG
041			_aeng
100			_aWolpin, Brian M. _eAutor _954562
245			_aDaraxonrasib in previously treated advanced RAS-Mutated pancreatic Cancer
300			_apáginas: 1790-1802
520			_aBackground: Current therapies for patients with pancreatic ductal adenocarcinoma (PDAC) provide modest benefit. Activating RAS mutations occur in more than 90% of PDAC tumors. Daraxonrasib (RMC-6236) is an oral RAS(ON) multiselective inhibitor that targets guanosine triphosphate–bound mutant and wild-type RAS. Methods: In this phase 1–2 study, we evaluated daraxonrasib in patients with advanced solid tumors with activating RAS mutations. Patients received 10 to 400 mg of daraxonrasib orally once daily; 300 mg was selected as the phase 3 dose. The primary end point was safety. Pharmacokinetics and antitumor activity were secondary end points. This report focuses on the 168 study patients with previously treated RAS-mutated PDAC. Results: Among the 168 patients with PDAC who received daraxonrasib at a dose of 300 mg or less, treatment-related adverse events of any grade were reported in 96%; such events of grade 3 or higher were reported in 30%. Treatment-related adverse events that occurred in at least 10% of the patients included rash, diarrhea, nausea, stomatitis or mucositis, vomiting, and fatigue. In a subgroup of 26 patients with RAS G12 mutations who were treated with second-line daraxonrasib at a dose of 300 mg, an objective response to therapy was reported in 35% (95% confidence interval [CI], 17 to 56). The median duration of response was 8.2 months (95% CI, 3.8 to not evaluable), with median values of 8.5 months for progression-free survival and 13.1 months for overall survival. Among the 38 patients with RAS G12, G13, or Q61 mutations, 29% (95% CI, 15 to 46) had an objective response. The median duration of response was 8.2 months (95% CI, 3.8 to 8.8), with median values of 8.1 months for progression-free survival and 15.6 months for overall survival. Conclusions: Daraxonrasib was associated with treatment-related adverse events of grade 3 or higher in one third of patients with previously treated RAS-mutated PDAC; antitumor activity was also reported.
650			_aCÁNCER _91231
650			_aCÁNCER DEL TRACTO GASTROINTESTINAL _953776
650			_aGASTROENTEROLOGÍA _912562
650			_aHEMATOLOGÍA _97422
650			_aONCOLOGÍA _912240
650			_aGENÉTICA GENERAL _954107
700			_aPark, Wungki _954563
700			_aGarrido-Laguna, Ignacio _954564
700			_aSpira, Alexander _954565
700			_aStarodub, Alexander _954566
700			_aSommerhalder, David _954567
700			_aPunekar, Salman R. _954568
773	0		_022717 _922676 _dMassachusetts NEJM Group _oNEJM015 _tThe New England Journal of Medicine _wESSALUD _x0028-4793
942			_cARTICULOS _e2026-08-31 _zsqb
999			_c22928 _d22928