{"id":325853,"date":"2022-05-12T09:52:39","date_gmt":"2022-05-12T07:52:39","guid":{"rendered":"https:\/\/medizinonline.com\/the-first-targeted-therapy-for-kras-g12c-mutation-1\/"},"modified":"2022-05-12T09:52:39","modified_gmt":"2022-05-12T07:52:39","slug":"the-first-targeted-therapy-for-kras-g12c-mutation-1","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/the-first-targeted-therapy-for-kras-g12c-mutation-1\/","title":{"rendered":"The first targeted therapy for KRAS G12C mutation [1]."},"content":{"rendered":"

After decades of effort, it is now possible for the first time to provide patients with KRAS G12C-mutated non-small cell lung cancer with an effective targeted therapy [1,2]. In the pivotal trial, the highly selective KRAS G12C inhibitor resulted in a rapid and sustained response in heavily pretreated patients [2]. The 2-year long-term follow-up also showed promising results [3].<\/strong><\/p>\n

<\/p>\n

Activating (KRAS) mutations* are the most common oncogenic driver mutations in non-small cell lung cancer (NSCLC). The most common of these is the KRAS G12C mutation, which is detectable in approximately 13% of all adenocarcinomas [2]. With the highly selective KRAS G12C inhibitor Lumykras\u00ae (Sotorasib), adult patients with locally advanced or metastatic non-squamous NSCLC with KRAS G12C mutation who have experienced progression after prior treatment with platinum-based chemotherapy and\/or anti-PD-1\/-PD-L1 immunotherapy now have access to an effective targeted therapy for the first time after decades of research. It is well tolerated and patient-friendly thanks to once-daily oral administration [1].<\/p>\n

CodeBreaK 100: rapid and sustained response [2].<\/h2>\n

The open-label, single-arm, multicenter Phase II CodeBreaK 100 trial evaluated the efficacy and safety of Lumykras\u00ae in patients with locally advanced or metastatic KRAS G12C-mutated NSCLC whose disease had progressed on standard therapies. Patients with stable brain metastases were also included in the study. Patients received a once-daily oral dose of 960 mg Lumykras\u00ae until disease progression [2].<\/p>\n

The primary endpoint was objective response rate (ORR), which was evaluated by an independent central committee according to the Response Evaluation Criteria in Solid Tumors<\/em> (RECIST 1.1) criteria. The main secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and tolerability. With Lumykras\u00ae treatment, 37.1% of patients had an objective response (ORR; 95% CI: 28.6-46.2). Patients responded not only rapidly – within a median of 1.4 months – but also durably, with a median DOR of 11.1 months (95% CI: 6.9 – not evaluable). Lumykras\u00ae measured a decrease in tumor burden in 82.3% of patients (Figure);<\/strong> patients who responded to Lumykras\u00ae treatment showed an average tumor reduction of 60%. Treatment achieved a median (m)PFS of 6.8 months (95% CI, 5.1 – 8.2) [2].<\/p>\n

In the 2-year long-term follow-up of 174 patients from the above-mentioned phase II and from the phase I study, the ORR increased to 40.7% (95% CI: 33.3 – 48.4) with an mDOR of 12.3 months (95% CI: 7.1-15.0). A DCR of 83.7% (95% CI: 77.3-88.9) was achieved and the mOS was 12.5 months (95% CI: 10.0 – 17.8). The OS rate after the first year was 50.8% (95% CI: 42.8-58.2) and 32.5% (95% CI: 25.0-40.2) of patients were still alive after the second year [3].<\/p>\n

*KRAS=Kirstenrat sarcoma virus oncogene homologue<\/em> <\/p>\n

\"\"<\/p>\n

Figure<\/strong>: Treatment response in the CodeBreaK 100 trial measured as best percent change from baseline in tumor burden in 121 evaluable patients. NE=not evaluable, PD=progressive disease, SD=stable disease, PR=partial response, CR=complete response. Adapted from [2]<\/em><\/p>\n

 <\/p>\n

Favorable tolerability profile also from the patient’s point of view [2,4]<\/h2>\n

The overall safety profile of Lumykras\u00ae proved to be well manageable. Treatment-related adverse events (TRAEs) occurred in 69.8% of patients and were mainly mild (\u2264 grade 2). The most common TRAEs reported with Lumykras\u00ae were diarrhea (32%), nausea (19%), and elevated liver enzymes (15% ASAT, 15% ALT). Treatment-related treatment discontinuations occurred in 7% of participants [2]. No new safety signals were registered in long-term follow-up [3]. Also, the majority of study participants reported no distress from adverse effects of Lumykras\u00ae treatment in a health-related quality of life questionnaire [4].<\/p>\n

Conclusion<\/h2>\n

After more than 40 years of research, the approval of Lumykras\u00ae makes targeted therapy available for the first time to NSCLC patients with KRAS G12C mutation [1]. This shows promising clinical results in the CodeBreak100 trial and long-term follow-up compared with historical treatments in NSCLC [2, 3, 5]. The KRAS G12C inhibitor can achieve a rapid and sustained response even in heavily pretreated patients, while also having a favorable safety profile when used orally [1-3].  <\/p>\n

 <\/p>\n

Literature<\/strong><\/p>\n

 <\/p>\n

1.                   Lumykras\u00ae (Sotorasib) Current Product Information at www.swissmedicinfo.ch.<\/em><\/span><\/div>\n
2.              Skoulidis F et al. Sotorasib for lung cancers with KRAS p. G12C mutation.<\/em> New England Journal of Medicine, 2021. 384(25): p. 2371-2381.<\/span><\/div>\n
3.              Dy GK et al. Long-term Outcomes With Sotorasib in Pre-treated KRAS p.G12C Mutated NSCLC: 2-year Analysis of CodeBreaK 100 Presented at American Association for Cancer Research (AACR) Annual Meeting, April 8-13, 2022; New Orleans.<\/span><\/div>\n
4.              Spira AI et al. Patient-reported outcomes (PRO) from the phase 2 CodeBreaK 100 trial evaluating sotorasib in KRAS p. G12C mutated non-small cell lung cancer (NSCLC)<\/em>. 2021, Wolters Kluwer Health.<\/span><\/div>\n
5.              Horn L et al. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).<\/em> J Clin Oncol, 2017. 35(35): p. 3924-3933.<\/span><\/div>\n

 <\/p>\n

References can be requested through professionals at medinfo-ch@amgen.com.<\/p>\n

CH-510-0322-00007<\/p>\n

Brief technical information Lumykras\u00ae <\/span><\/span><\/a><\/p>\n

Contribution online since 12.05.2022<\/p>\n","protected":false},"excerpt":{"rendered":"

After decades of effort, it is now possible for the first time to provide patients with KRAS G12C-mutated non-small cell lung cancer with an effective targeted therapy [1,2]. In the…<\/p>\n","protected":false},"author":14,"featured_media":120366,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Non-small cell lung cancer","footnotes":""},"category":[11500,11370,11455,11548,11503],"tags":[],"powerkit_post_featured":[],"class_list":["post-325853","post","type-post","status-publish","format-standard","has-post-thumbnail","category-news-en","category-oncology","category-pneumology","category-rx-en","category-studies","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-03 04:30:50","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":325860,"slug":"la-premiere-therapie-ciblee-pour-la-mutation-g12c-du-gene-kras-1","post_title":"La premi\u00e8re th\u00e9rapie cibl\u00e9e pour la mutation G12C du g\u00e8ne KRAS [1]","href":"https:\/\/medizinonline.com\/fr\/la-premiere-therapie-ciblee-pour-la-mutation-g12c-du-gene-kras-1\/"},"it_IT":{"locale":"it_IT","id":325867,"slug":"la-prima-terapia-mirata-per-la-mutazione-kras-g12c-1","post_title":"La prima terapia mirata per la mutazione KRAS G12C [1].","href":"https:\/\/medizinonline.com\/it\/la-prima-terapia-mirata-per-la-mutazione-kras-g12c-1\/"},"pt_PT":{"locale":"pt_PT","id":325874,"slug":"a-primeira-terapia-direccionada-para-a-mutacao-kras-g12c-1","post_title":"A primeira terapia direccionada para a muta\u00e7\u00e3o KRAS G12C [1].","href":"https:\/\/medizinonline.com\/pt-pt\/a-primeira-terapia-direccionada-para-a-mutacao-kras-g12c-1\/"},"es_ES":{"locale":"es_ES","id":325882,"slug":"la-primera-terapia-dirigida-contra-la-mutacion-g12c-de-kras-1","post_title":"La primera terapia dirigida contra la mutaci\u00f3n G12C de KRAS [1].","href":"https:\/\/medizinonline.com\/es\/la-primera-terapia-dirigida-contra-la-mutacion-g12c-de-kras-1\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/325853","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/14"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=325853"}],"version-history":[{"count":0,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/325853\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/120366"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=325853"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=325853"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=325853"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=325853"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}