{"id":2910,"date":"2023-10-26T21:24:27","date_gmt":"2023-10-26T21:24:27","guid":{"rendered":"http:\/\/drhimanshuyadav.com\/a-combination-that-beats-standard-treatments-for-metastatic-colorectal-cancer\/"},"modified":"2023-10-26T21:24:27","modified_gmt":"2023-10-26T21:24:27","slug":"a-combination-that-beats-standard-treatments-for-metastatic-colorectal-cancer","status":"publish","type":"post","link":"https:\/\/drhimanshuyadav.com\/blog\/a-combination-that-beats-standard-treatments-for-metastatic-colorectal-cancer\/","title":{"rendered":"A combination that beats standard treatments for metastatic colorectal cancer"},"content":{"rendered":"<div data-component=\"ArticleContent\">\n<div class=\"article__content--header\">\n<div class=\"article__posted-date\">\n<p>    October 23, 2023 <\/p>\n<p>    2 minute read <\/p>\n<\/p><\/div>\n<\/div>\n<div class=\"mobile-trust-box\">\n<div class=\"row\">\n<div class=\"col-12 col-md-5 d-xl-none\">\n<div class=\"trust-box\">\n<div class=\"trust-box-logo d-none d-md-block\">\n          <img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.healio.com\/~\/media\/h5\/feature\/news\/publogos\/hot.svg?h=24&amp;w=141&amp;la=en&amp;hash=2F86D471C8514C0E334E329AA799E8B4\" height=\"24\" width=\"141\" class=\"logo-img\" alt=\"Hemonk today's logo\"\/>\n        <\/div>\n<\/p><\/div>\n<\/p><\/div>\n<div class=\"col-12 col-md-6 offset-md-1 offset-xl-0 col-xl-12\">\n<div class=\"d-none\" data-component=\"EmailTopicAlert\" data-module=\"Subspecialty Email Topic Alerts Top\" data-manage-email-link=\"\/footer\/account-information\/my-account\/email-subscriptions-and-alerts#emailAlerts\">\n  <hidden data-setting-item=\"d265901d-6d37-49c7-a8f6-c7bf19a02509\"\/><br \/>\n  <hidden data-crm-source=\"Subspecialty Topic Alert\"\/><\/p>\n<div class=\"email-alert-button d-none\" data-topic-button=\"not-subscribed\">\n<p>&#13;<br \/>\n      <span data-module-track-action=\"Email Alerts TOP_Click_Healio News Article\" data-module-track-label=\"Email Alerts TOP_Healio News Article\">&#13;<br \/>\n        <i class=\"fas fa-plus-circle\"\/>Add topics to email alerts<br \/>\n      <\/span>&#13;\n    <\/p>\n<div class=\"email-alert-inner collapse u358a41b6e4864105874d7342ef44af1e\">\n<div class=\"email-alert-dialogue\">\n<p>Receive an email when a new article is posted <span data-content=\"topic-title\"\/>&#13;\n        <\/p>\n<div class=\"d-none\" data-sign-up-type=\"unknown\">\n<p>          Enter your email address to receive emails when new articles are posted. <span data-content=\"topic-title\"\/>.<\/p><\/div>\n<\/p><\/div>\n<p>      <button type=\"button\" class=\"btn btn-primary\" data-loading-text=\"Loading &lt;i class=\" fa=\"\" fa-spinner=\"\" fa-spin=\"\">&#8221; data-action=&#8221;subscribe&#8221;> Subscribe<br \/>\n      <\/button>\n    <\/div>\n<\/p><\/div>\n<div class=\"d-none\" data-topic-modal=\"failed\">    <strong>Your request could not be processed. Please try again later. If you continue to experience this issue, please contact us at customerservice@slackinc.com.<\/strong>  <\/p>\n<p><button data-dismiss=\"modal\" class=\"btn btn-primary btn-lg btn-block\">Return to Helio<\/button><\/p>\n<\/div>\n<\/div><\/div>\n<\/p><\/div>\n<\/p><\/div>\n<h4>Important points:<\/h4>\n<ul>\n<li>Sotorasib and panitumumab prolonged PFS compared to standard of care.<\/li>\n<li>Grade 3 or higher adverse events occurred less frequently with the combination.<\/li>\n<\/ul>\n<p>MADRID \u2014 Sotorasib and panitumumab prolonged PFS compared to standard treatment in chemotherapy-resistant patients <em>KRA<\/em><em>S<\/em> G12C mutations in metastatic colorectal cancer, study results presented at the ESMO conference showed.<\/p>\n<p>The combination also provided benefits in terms of response rate, duration of response, and disease control, according to study results published at the same time. <em>New England Medical Journal<\/em>.<\/p>\n<figure class=\"figure article__og-image\">&#13;\n    <picture>&#13;<source srcset=\"https:\/\/www.healio.comhttps:\/\/www.healio.comhttps:\/\/www.healio.com\/~\/media\/slack-news\/hemonc\/misc\/infographics\/hot-infographics\/2023\/10_october\/hot1023pietrantonio_esmo_graphic_01.webp?w=476\" media=\"(max-width: 768px)\">&#13;<source srcset=\"https:\/\/www.healio.com\/~\/media\/slack-news\/hemonc\/misc\/infographics\/hot-infographics\/2023\/10_october\/hot1023pietrantonio_esmo_graphic_01.webp?w=800\" media=\"(max-width: 992px)\">&#13;<source srcset=\"https:\/\/www.healio.com\/~\/media\/slack-news\/hemonc\/misc\/infographics\/hot-infographics\/2023\/10_october\/hot1023pietrantonio_esmo_graphic_01.webp?w=595\" media=\"(max-width: 1200px)\">&#13;<source srcset=\"https:\/\/www.healio.comhttps:\/\/www.healio.comhttps:\/\/www.healio.com\/~\/media\/slack-news\/hemonc\/misc\/infographics\/hot-infographics\/2023\/10_october\/hot1023pietrantonio_esmo_graphic_01.webp?w=476\" media=\"(min-width: 1200px)\">&#13;<source srcset=\"https:\/\/www.healio.comhttps:\/\/www.healio.comhttps:\/\/www.healio.com\/~\/media\/slack-news\/hemonc\/misc\/infographics\/hot-infographics\/2023\/10_october\/hot1023pietrantonio_esmo_graphic_01.webp?w=476\">&#13;<br \/>\n&#13;<br \/>\n      <img decoding=\"async\" src=\"https:\/\/www.healio.com\/~\/media\/slack-news\/hemonc\/misc\/infographics\/hot-infographics\/2023\/10_october\/hot1023pietrantonio_esmo_graphic_01.jpg?w=800\" alt=\"Diagram showing objective response rate\" class=\"figure-img img-fluid\" width=\"800\"\/>&#13;<br \/>\n    <\/source><\/source><\/source><\/source><\/source><\/picture>&#13;<figcaption class=\"figure-caption\">&#13;<br \/>\n      &#13;<br \/>\n    <\/figcaption>&#13;<br \/>\n  <\/figure>\n<p>KRAS G12C mutations are present in 3% to 4% of metastatic colorectal cancers. Based on the research background, monotherapy with KRAS G12C inhibitors has demonstrated only modest efficacy.<\/p>\n<p>      <strong>Dr. Filippo Pietrantonio,<\/strong> Gastrointestinal medical oncologists at the Fondazione IRCCS Istituto Nazionale dei Tumori in Italy conducted the randomized phase 3 CodeBreaK trial to evaluate the use of sotorasib (Lumakras, Amgen) in combination. <em>class<\/em> Panitumumab (Vectibix, Amgen), a G12C inhibitor and fully human monoclonal anti-EGFR antibody, may improve outcomes.<\/p>\n<p>The multicenter, open-label study included 160 patients with chemotherapy-resistant metastatic colorectal cancer who had not received prior drug therapy. <em>class<\/em> G12C inhibitor.<\/p>\n<p>Researchers randomly assigned 53 patients to receive sotorasib 960 mg\/day and panitumumab 6 mg\/kg intravenously.  53 patients received sotorasib 240 mg daily and panitumumab 6 mg\/kg IV.  Fifty-four patients received investigator&#8217;s choice of either trifluridine-tipiracil (Lonsurf; Taiho Oncology, Servier) or regorafenib (Stivarga, Bayer).<\/p>\n<p>PFS by blinded independent central review served as the primary endpoint. Key secondary endpoints include OS, objective response, and disease control rate.<\/p>\n<p>Median follow-up was 7.8 months (range, 0.1-13.9 months).<\/p>\n<p>The study met its primary endpoint, as the combination of both sotorasib and panitumumab resulted in significant PFS improvements compared to standard care (sotorasib 960 mg, HR = 0.49; 95% CI, 0.3-0.8; sotorasib 240 mg, HR = 0.58; 95% CI, 0.36-0.93).<\/p>\n<p>At the time of data cutoff, OS data remained immature.<\/p>\n<p>Researchers reported that median PFS was longer in both the sotorasib and panitumumab groups (sotorasib 960 mg, 5.6 months; sotorasib 240 mg, 3.9 months; standard care, 2.2 months).<\/p>\n<p>Results also showed higher ORR (sotorasib 960 mg, 26.4%; sotorasib 240 mg, 5.7%, standard of care, 0%) and higher disease control rates (sotorasib 960 mg, 71.7%; sotorasib 240 mg, 67.9%, standard treatment, 46.3%).<\/p>\n<p>Median duration of response was 4.4 months in the sotorasib 960 group but not reached in the sotorasib 240 mg group.<\/p>\n<p>Grade 3 or higher treatment-related adverse events occurred in 35.8% of patients in the sotorasib 960 mg group, 30.2% of patients in the sotorasib 240 mg group, and 43.1% of patients in the standard treatment group.<\/p>\n<p>Grade 3 or higher treatment-related events reported in patients in the sotorasib 960 mg group included dermatitis acneiformis (11.3%), hypomagnesemia (5.7%), and rash (5.7%). Ta. Grade 3 or higher treatment-related adverse events observed in the sotorasib 240 mg group included hypomagnesemia (7.5%) and diarrhea (5.7%).<\/p>\n<p>In the standard treatment arm, grade 3 or higher treatment-related adverse events included neutropenia (23.5%), anemia (5.9%), and hypertension (5.9%).<\/p>\n<p>No fatal treatment-related adverse events occurred.<\/p>\n<div class=\"publisher-logo\">\n    <span>Issuer:<\/span><br \/>\n    <img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.healio.com\/~\/media\/h5\/feature\/news\/publogos\/hot.svg?h=24&amp;w=141&amp;la=en&amp;hash=2F86D471C8514C0E334E329AA799E8B4\" class=\"logo-img\" width=\"141\" height=\"24\" alt=\"Hemonk today's logo\"\/>\n  <\/div>\n<div class=\"sources-disclosures\">\n  <a class=\"title\" data-toggle=\"collapse\" data-target=\".sources-disclosures-toggle\" aria-controls=\"sources-disclosures-content\">Information source\/disclosure information<i class=\"fas\"\/><\/p>\n<p class=\"collapse-label show\">collapse<\/p>\n<p>&#13;<br \/>\n  <\/a><\/p>\n<div id=\"sources-disclosures-content\" class=\"sources-disclosures-toggle collapse show\">\n<div class=\"sources\">\n        <strong>    sauce: <\/strong><\/p>\n<p class=\"citation\">Pietrantonio F et al. Abstract LBA10. Presented at the European Society of Clinical Oncology Congress.  October 20-24, 2023. Madrid.<\/p>\n<\/p><\/div>\n<p>&#13;<br \/>\n        <strong> Disclosure: <\/strong>Pietrantonio reports financial relationships with companies including Amgen, Astellas, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Eli Lilly &#038; Company, Incyte, Merck Serono, and Merck Sharp &#038; Dohme. See the study for all researchers&#8217; relevant financial disclosures.\n      <\/p>\n<\/p><\/div>\n<\/div>\n<div class=\"article__content--footer\">\n<div class=\"perspective\">\n<p>  <a id=\"B0D39B00BA4E478E8999208977BB2491\"\/><\/p>\n<p>  <a id=\"perspective\" name=\"perspective\"\/><\/p>\n<h2 class=\"title\">perspective<\/h2>\n<p>  <a class=\"back-to-top\" href=\"\/blog\/#top\">    Return to top <i class=\"far fa-arrow-up\"\/> <\/a><\/p>\n<div class=\"perspective-body\">\n<p class=\"name\">Miriam Koopman, MD<\/p>\n<p xmlns=\"http:\/\/www.w3.org\/1999\/xhtml\">CodeBreaK 300 is the first randomized phase 3 trial investigating the efficacy of combination therapy. <i>class<\/i> G12C inhibition and anti-<i>EGFR<\/i> Treatment of previously treated metastatic colorectal cancer. <\/p>\n<p xmlns=\"http:\/\/www.w3.org\/1999\/xhtml\">We saw encouraging results with high rates of tumor regression from baseline and a significant benefit in PFS in highly pretreated patients.<\/p>\n<p xmlns=\"http:\/\/www.w3.org\/1999\/xhtml\">Comparable results between the CodeBreaK 300 control arm and a previously published phase 3 study with trifluridine-tipiracil and regorafenib support the validity of the results.<\/p>\n<p xmlns=\"http:\/\/www.w3.org\/1999\/xhtml\">However, since trifluridine tipiracil and bevacizumab (Avastin, Genentech) are the current late-stage standard drugs, it is necessary to compare sotorasib plus panitumumab and trifluridine tipiracil plus bevacizumab for the following patients: <i>class<\/i> G12C mutant tumor.<\/p>\n<p xmlns=\"http:\/\/www.w3.org\/1999\/xhtml\">OS and quality of life results will determine whether sotorasib plus panitumumab is the final standard of care for patients who: <i>class<\/i> G12C mutation disease. If positive, this combination should only be used in patients who meet the CodeBreaK eligibility criteria, and as only 3% of patients overall have performance status 2, further data on this subset of patients is needed.<\/p>\n<p xmlns=\"http:\/\/www.w3.org\/1999\/xhtml\">Other first- and second-line studies combining RAS inhibitors and anti-anti-inflammatory drugs<i>EGFR<\/i> Chemotherapy is also continuing. Moving to an earlier line of treatment that combines chemotherapy may provide additional benefit to patients.<\/p>\n<div class=\"position\">\n<p>Miriam Koopman, MD<\/p>\n<p>Utrecht University Medical Center<\/p>\n<\/p><\/div>\n<p>&#13;<br \/>\n      <strong> Disclosure: <\/strong> Koopman reports financial or other relationships with Amgen, Bayer, Bristol-Myers Squibb, GSK, Merck Serono, Servier, Sanofi and other entities.\n    <\/p>\n<\/p><\/div>\n<\/div>\n<div class=\"d-none\" data-component=\"EmailTopicAlert\" data-module=\"Subspecialty Email Topic Alerts Top\" data-manage-email-link=\"\/footer\/account-information\/my-account\/email-subscriptions-and-alerts#emailAlerts\">\n  <hidden data-setting-item=\"d265901d-6d37-49c7-a8f6-c7bf19a02509\"\/><br \/>\n  <hidden data-crm-source=\"Subspecialty Topic Alert\"\/><\/p>\n<div class=\"email-alert-button d-none\" data-topic-button=\"not-subscribed\">\n<p>&#13;<br \/>\n      <span data-module-track-action=\"Email Alerts TOP_Click_Healio News Article\" data-module-track-label=\"Email Alerts TOP_Healio News Article\">&#13;<br \/>\n        <i class=\"fas fa-plus-circle\"\/>Add topics to email alerts<br \/>\n      <\/span>&#13;\n    <\/p>\n<div class=\"email-alert-inner collapse u358a41b6e4864105874d7342ef44af1e\">\n<div class=\"email-alert-dialogue\">\n<p>Receive an email when a new article is posted <span data-content=\"topic-title\"\/>&#13;\n        <\/p>\n<div class=\"d-none\" data-sign-up-type=\"unknown\">\n<p>          Enter your email address to receive emails when new articles are posted. <span data-content=\"topic-title\"\/>.<\/p><\/div>\n<\/p><\/div>\n<p>      <button type=\"button\" class=\"btn btn-primary\" data-loading-text=\"Loading &lt;i class=\" fa=\"\" fa-spinner=\"\" fa-spin=\"\">&#8221; data-action=&#8221;subscribe&#8221;> Subscribe<br \/>\n      <\/button>\n    <\/div>\n<\/p><\/div>\n<div class=\"d-none\" data-topic-modal=\"failed\">    <strong>Your request could not be processed. 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