Good news! Cancer is history (soon)!
"A daily pill for pancreatic cancer could be a game changer—doubling survival time with fewer side effects than chemotherapy; patients who took daraxonrasib lived ~13.2 months, compared with 6.6–6.7 months for those who did not, per the results of a clinical trial of 500 participants presented at the American Society of Clinical Oncology’s annual meeting in Chicago this past weekend. ..."
"Chemotherapy remains the mainstay systemic treatment for pancreatic ductal adenocarcinoma (PDAC) and the disease continues to hold a dismal prognosis. Most PDACs (>90%) are driven by mutant forms of KRAS, which were historically considered ‘undruggable’; however, recent pharmacological breakthroughs in targeting this protein are providing new hope. Now, new data from a phase I/II trial demonstrate the promising efficacy of daraxonrasib — a novel non-covalent inhibitor that targets the active ‘ON’ conformations of mutant and wild-type KRAS, HRAS and NRAS — in this disease. ..."
From the abstract:
"Background
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 endpoints 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 ...
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. ..."
Pan-RAS inhibitor daraxonrasib shows promise in pancreatic cancer (no public access)
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