{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:17:22Z","timestamp":1790738242375,"version":"4.1.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Tumor molecular profiling is recommended in pancreatic ductal adenocarcinoma (PDAC). However, the predictive and prognostic value of\n              <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n              variants on clinical outcomes including response to standard therapies remains unknown.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              In this retrospective analysis using real-world data from patients with early-stage (I to III) and metastatic PDAC who underwent molecular profiling via referrals to Perthera or the PanCAN Know Your Tumor program, patients included were 18 years and older, received standard chemotherapy in the first- and second-line setting, and had complete records. Main outcomes were overall survival (OS) and progression-free survival (PFS) measured from the date of diagnosis of metastatic\/recurrent metastatic disease stratified by the\n              <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n              variants and chemotherapy regimen. OS and PFS on first- or second-line therapies were analyzed using Cox regression. Outcomes from each subgroup were compared with reference cohort G12D\/V using a Bonferroni-adjusted significance threshold of \u03b1 = .00714 (0.05\/7).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              A total of 1359 patients (median [range] age, 64 [28-94] years; 689 [50.7%] male; 707 [52.0%] White) were included.\n              <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n              wild type had significantly longer OS compared with G12D\/V (2.1\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              1.4 years; hazard ratio [HR], 0.61 [95% CI, 0.48 to 0.77];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt; .0001). Q61 had shorter OS (1.1\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              1.5 years; HR, 2.28 [95% CI, 1.33 to 3.92];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .0027) and PFS (3.13\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              9.03 months; HR, 2.54 [95% CI, 1.43 to 4.52];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .0015) on first-line fluorouracil-based therapy compared with G12D\/V. G12R had numerically longer OS (1.8\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              1.5 years; HR, 0.69 [95% CI, 0.48 to 0.98];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .0366) and PFS (12.17\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              9.03 months; HR, 0.6 [95% CI, 0.41 to 0.88];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .0091) on first-line fluorouracil-based therapy compared with G12D\/V.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n              variants are associated with survival and may be predictive of response to standard therapies. A molecularly driven, variant-specific approach is recommended to guide PDAC treatment and better inform prognosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-24-00684","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T19:59:08Z","timestamp":1755719948000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Evaluating the Effect of\n            <i>KRAS<\/i>\n            Variants on Survival Outcomes and Therapy Response in Pancreatic Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-1926","authenticated-orcid":true,"given":"Matthew I.","family":"Ebia","sequence":"first","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-3849","authenticated-orcid":true,"given":"Edik M.","family":"Blais","sequence":"additional","affiliation":[{"name":"Perthera, Inc, McLean, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8254-6474","authenticated-orcid":true,"given":"Yujie","family":"Cui","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9146-5572","authenticated-orcid":false,"suffix":"III","given":"Emanuel F.","family":"Petricoin","sequence":"additional","affiliation":[{"name":"Perthera, Inc, McLean, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-9041","authenticated-orcid":true,"given":"Michael","family":"Pishvaian","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Gaddam","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-1406","authenticated-orcid":true,"given":"Jun","family":"Gong","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9000-7040","authenticated-orcid":true,"given":"Arsen","family":"Osipov","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-9177","authenticated-orcid":true,"given":"Andrew E.","family":"Hendifar","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.4708"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002234"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.014"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.22"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01366-1"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.2565"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.12.014"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep21949"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00534-006-1166-5"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14246223"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2021.02.003"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00505-0"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3420"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.08.002"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmogo.2023.100030"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyac179"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.4_suppl.735"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0531"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooz045"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2344"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7744"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.e16259"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.76695"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abn2694"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3581"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01688"},{"key":"e_1_3_7_30_2","doi-asserted-by":"crossref","unstructured":"Jiang L Menard M Weller C et al: RMC-9805 a first-in-class mutant-selective covalent and oral KRASG12D(ON) inhibitor that induces apoptosis and drives tumor regression in preclinical models of KRASG12D cancers. Presented at the American Association for Cancer Research 2023","DOI":"10.1158\/1538-7445.AM2023-526"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-24-00684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T19:59:10Z","timestamp":1755719950000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-24-00684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1200\/PO-24-00684"],"URL":"https:\/\/doi.org\/10.1200\/po-24-00684","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2024-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-29","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400684"}}