Guglielmo Vetere, Marco Maria Germani, Carlotta Antoniotti, Lisa Salvatore, Filippo Pietrantonio, Sara Lonardi, Maria Bensi, Filippo Ghelardi, Maria Alessandra Calegari, Rossana Intini, Alessandro Minelli, Francesco Giulio Sullo, Chiara Boccaccio, Ada Taravella, Alberto Puccini, Daniele Lavacchi, Laura Noto, Massimiliano Salati, Mario Scartozzi, Chiara Cremolini
{"title":"靶向治疗对BRAF V600E突变转移性结直肠癌患者反应深度和早期肿瘤缩小的影响","authors":"Guglielmo Vetere, Marco Maria Germani, Carlotta Antoniotti, Lisa Salvatore, Filippo Pietrantonio, Sara Lonardi, Maria Bensi, Filippo Ghelardi, Maria Alessandra Calegari, Rossana Intini, Alessandro Minelli, Francesco Giulio Sullo, Chiara Boccaccio, Ada Taravella, Alberto Puccini, Daniele Lavacchi, Laura Noto, Massimiliano Salati, Mario Scartozzi, Chiara Cremolini","doi":"10.1177/17588359241299975","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Encorafenib plus cetuximab (EC) is the standard of care for pre-treated <i>BRAF</i> <sup><i>V600E</i></sup> mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents.</p><p><strong>Objectives: </strong>We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics.</p><p><strong>Design: </strong>This is a retrospective real-world cohort study of <i>BRAF</i> <sup><i>V600E</i></sup> mutated mCRC patients treated with second-line EC ± B at 20 Italian centres.</p><p><strong>Methods: </strong>Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients.</p><p><strong>Results: </strong>A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases (<i>p</i> = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR (<i>p</i> = 0.005) and a lower rate of ETS (<i>p</i> = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR)<sub>DpR</sub> <sub>⩾</sub> <sub>30%</sub>: 0.52, 95% CI: 0.30-0.90, <i>p</i> = 0.02) and median cut-off values (HR<sub>DpR⩾15%</sub>: 0.55, 95% CI: 0.33-0.92, <i>p</i> = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78-0.98, <i>p</i> = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR (<i>p</i> <sub>DpR⩾30%</sub> = 0.04; <i>p</i> <sub>DpR⩾15%</sub> = 0.04; <i>p</i> <sub>cont.</sub> = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected.</p><p><strong>Conclusion: </strong>A DpR of at least 15% independently predicts PFS benefit in <i>BRAF</i> <sup><i>V600E</i></sup> mutated mCRC patients treated with second-line EC ± B.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359241299975"},"PeriodicalIF":4.3000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705328/pdf/","citationCount":"0","resultStr":"{\"title\":\"Prognostic impact of depth of response and early tumour shrinkage in patients with <i>BRAF</i> <sup><i>V600E</i></sup> -mutated metastatic colorectal cancer treated with targeted therapy.\",\"authors\":\"Guglielmo Vetere, Marco Maria Germani, Carlotta Antoniotti, Lisa Salvatore, Filippo Pietrantonio, Sara Lonardi, Maria Bensi, Filippo Ghelardi, Maria Alessandra Calegari, Rossana Intini, Alessandro Minelli, Francesco Giulio Sullo, Chiara Boccaccio, Ada Taravella, Alberto Puccini, Daniele Lavacchi, Laura Noto, Massimiliano Salati, Mario Scartozzi, Chiara Cremolini\",\"doi\":\"10.1177/17588359241299975\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Encorafenib plus cetuximab (EC) is the standard of care for pre-treated <i>BRAF</i> <sup><i>V600E</i></sup> mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents.</p><p><strong>Objectives: </strong>We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics.</p><p><strong>Design: </strong>This is a retrospective real-world cohort study of <i>BRAF</i> <sup><i>V600E</i></sup> mutated mCRC patients treated with second-line EC ± B at 20 Italian centres.</p><p><strong>Methods: </strong>Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients.</p><p><strong>Results: </strong>A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases (<i>p</i> = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR (<i>p</i> = 0.005) and a lower rate of ETS (<i>p</i> = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR)<sub>DpR</sub> <sub>⩾</sub> <sub>30%</sub>: 0.52, 95% CI: 0.30-0.90, <i>p</i> = 0.02) and median cut-off values (HR<sub>DpR⩾15%</sub>: 0.55, 95% CI: 0.33-0.92, <i>p</i> = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78-0.98, <i>p</i> = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR (<i>p</i> <sub>DpR⩾30%</sub> = 0.04; <i>p</i> <sub>DpR⩾15%</sub> = 0.04; <i>p</i> <sub>cont.</sub> = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected.</p><p><strong>Conclusion: </strong>A DpR of at least 15% independently predicts PFS benefit in <i>BRAF</i> <sup><i>V600E</i></sup> mutated mCRC patients treated with second-line EC ± B.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"17 \",\"pages\":\"17588359241299975\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-01-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705328/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241299975\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241299975","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Prognostic impact of depth of response and early tumour shrinkage in patients with BRAFV600E -mutated metastatic colorectal cancer treated with targeted therapy.
Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAFV600E mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents.
Objectives: We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics.
Design: This is a retrospective real-world cohort study of BRAFV600E mutated mCRC patients treated with second-line EC ± B at 20 Italian centres.
Methods: Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients.
Results: A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases (p = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR)DpR⩾30%: 0.52, 95% CI: 0.30-0.90, p = 0.02) and median cut-off values (HRDpR⩾15%: 0.55, 95% CI: 0.33-0.92, p = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78-0.98, p = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR (pDpR⩾30% = 0.04; pDpR⩾15% = 0.04; pcont. = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected.
Conclusion: A DpR of at least 15% independently predicts PFS benefit in BRAFV600E mutated mCRC patients treated with second-line EC ± B.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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