Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy
Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E 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 a...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-01-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359241299975 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Guglielmo Vetere |
| collection | DOAJ |
| description | Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E 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 BRAF V600E 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 (HR DpR⩾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 ( p DpR⩾30% = 0.04; p DpR⩾15% = 0.04; p cont. = 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 BRAF V600E mutated mCRC patients treated with second-line EC ± B. |
| format | Article |
| id | doaj-art-1464f24551934831b4a4c68ed414b705 |
| institution | Kabale University |
| issn | 1758-8359 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj-art-1464f24551934831b4a4c68ed414b7052025-01-07T10:03:53ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592025-01-011710.1177/17588359241299975Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapyGuglielmo VetereMarco Maria GermaniCarlotta AntoniottiLisa SalvatoreFilippo PietrantonioSara LonardiMaria BensiFilippo GhelardiMaria Alessandra CalegariRossana IntiniAlessandro MinelliFrancesco Giulio SulloChiara BoccaccioAda TaravellaAlberto PucciniDaniele LavacchiLaura NotoMassimiliano SalatiMario ScartozziChiara CremoliniBackground: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E 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 BRAF V600E 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 (HR DpR⩾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 ( p DpR⩾30% = 0.04; p DpR⩾15% = 0.04; p cont. = 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 BRAF V600E mutated mCRC patients treated with second-line EC ± B.https://doi.org/10.1177/17588359241299975 |
| spellingShingle | 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 Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy Therapeutic Advances in Medical Oncology |
| title | Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy |
| title_full | Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy |
| title_fullStr | Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy |
| title_full_unstemmed | Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy |
| title_short | Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy |
| title_sort | prognostic impact of depth of response and early tumour shrinkage in patients with mutated metastatic colorectal cancer treated with targeted therapy |
| url | https://doi.org/10.1177/17588359241299975 |
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