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We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg\/m2 and 500\u2009mg\/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg\/m2 and 400\u2009mg\/m2 plus 6\u2009mg\/kg, respectively). A total of 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65\u2009months).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 102 enrolled, 44 treated with irinotecan-cetuximab and 45 with modified ramucirumab were evaluable. Median PFS was 6.0 months vs 9.2\u2009months, respectively (hazard ratio = 0.75, P =\u2009.07; statistically significant by study design for P\u2009&amp;lt;\u2009.128). Response rate was 23% vs 36% (P =\u2009.27), and disease-control rate was 52% vs 73% (P\u2009=\u2009.05). Grade 3 or higher toxicity was equivalent. Overall survival was not significantly different at approximately 19\u2009months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Previous phase 3 trials without RAS genotyping rejected combining anti-epidermal growth factor receptor and anti-VEGF drugs. In this randomized multicenter phase 2 study for KRAS wild-type CRC (all previously bevacizumab treated), the addition of ramucirumab to irinotecan and cetuximab improved PFS and disease control rate, showing the combination is feasible and effective. Further, phase 3 trials with appropriate patient-selection are required. (NCT01079780)<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djae114","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T16:30:57Z","timestamp":1716395457000},"page":"1487-1494","source":"Crossref","is-referenced-by-count":9,"title":["Combining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with\/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208)"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9893-1529","authenticated-orcid":false,"given":"Howard S","family":"Hochster","sequence":"first","affiliation":[{"name":"Rutgers Cancer Institute , New Brunswick, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Catalano","sequence":"additional","affiliation":[{"name":"ECOG-ACRIN Biostatistics Center , Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Weitz","sequence":"additional","affiliation":[{"name":"ECOG-ACRIN Biostatistics Center , Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith P","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University Hospital , Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deirdre","family":"Cohen","sequence":"additional","affiliation":[{"name":"Mt Sinai Hospital , New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J","family":"O\u2019Dwyer","sequence":"additional","affiliation":[{"name":"University of Pennsylvania , Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan A","family":"Faller","sequence":"additional","affiliation":[{"name":"Missouri Baptist Medical Center Heartland NCORP , St Louis, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy S","family":"Kortmansky","sequence":"additional","affiliation":[{"name":"Yale Cancer Center , New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark H","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"University of Pennsylvania , Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheetal M","family":"Kricher","sequence":"additional","affiliation":[{"name":"Northwestern University , Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Lacy","sequence":"additional","affiliation":[{"name":"Yale Cancer Center , New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinz-Josef","family":"Lenz","sequence":"additional","affiliation":[{"name":"Norris Comprehensive Cancer Center , Los Angeles, CA, 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