Efficacy of Regorafenib and Trifluridine/Tipiracil According to Extended RAS Evaluation in Advanced Metastatic Colorectal Cancer Patients: A Multicenter Retrospective Analysis.

Autor: Basso M; Comprehensive Cancer Center, Fondazione Policlinico Universitario 'A Gemelli' - IRCCS, Largo Agostino Gemelli n 8, 00168, Rome, Italy. michele.basso@policlinicogemelli.it., Signorelli C; Medical Oncology Unit, Belcolle Hospital, ASL Viterbo, Viterbo, Italy., Calegari MA; Comprehensive Cancer Center, Fondazione Policlinico Universitario 'A Gemelli' - IRCCS, Largo Agostino Gemelli n 8, 00168, Rome, Italy., Lucchetti J; Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy., Zurlo IV; Medical Oncology, 'Vito Fazzi' Hospital, Lecce, Italy., Dell'Aquila E; Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Arrivi G; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Oncology Unit, Sant' Andrea University Hospital, Rome, Italy., Zoratto F; Medical Oncology Unit, ASL Latina, Latina, Italy., Santamaria F; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.; Medical Oncology A, Department of Hematology, Oncology and Dermatology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy., Saltarelli R; UOC Oncology, San Giovanni Evangelista Hospital, ASL RM5, Tivoli, RM, Italy., Trovato G; Medical Oncology, Catholic University of Sacred Heart, Rome, Italy., Caira G; Medical Oncology, Catholic University of Sacred Heart, Rome, Italy., Angotti L; Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy., Schirripa M; Medical Oncology Unit, Belcolle Hospital, ASL Viterbo, Viterbo, Italy., Anghelone A; Medical Oncology, Catholic University of Sacred Heart, Rome, Italy., Schietroma F; Medical Oncology, Catholic University of Sacred Heart, Rome, Italy., Chilelli MG; Medical Oncology Unit, Belcolle Hospital, ASL Viterbo, Viterbo, Italy., Salvatore L; Comprehensive Cancer Center, Fondazione Policlinico Universitario 'A Gemelli' - IRCCS, Largo Agostino Gemelli n 8, 00168, Rome, Italy.; Medical Oncology, Catholic University of Sacred Heart, Rome, Italy., Pozzo C; Comprehensive Cancer Center, Fondazione Policlinico Universitario 'A Gemelli' - IRCCS, Largo Agostino Gemelli n 8, 00168, Rome, Italy., Tortora G; Comprehensive Cancer Center, Fondazione Policlinico Universitario 'A Gemelli' - IRCCS, Largo Agostino Gemelli n 8, 00168, Rome, Italy.; Medical Oncology, Catholic University of Sacred Heart, Rome, Italy.
Jazyk: angličtina
Zdroj: Targeted oncology [Target Oncol] 2024 May; Vol. 19 (3), pp. 371-382. Date of Electronic Publication: 2024 Apr 13.
DOI: 10.1007/s11523-024-01050-3
Abstrakt: Background: There are few molecular markers driving treatment selection in later lines of treatment for advanced colorectal cancer patients. The vast majority of patients who progress after first- and second-line therapy undergo chemotherapy regardless of molecular data.
Objective: We aimed to assess the prognostic and predictive effects of specific RAS mutations on overall survival of patients receiving regorafenib (rego), trifluridine/tipiracil (TFD/TPI), or both.
Patients and Methods: This was a retrospective observational study based on data from a previous study of our research network, involving nine Italian institutions over a 10-year timeframe (2012-2022). Extended RAS analysis, involving KRAS exon 2-4 and NRAS exon 2-4, and BRAF were the main criteria for inclusion in this retrospective evaluation. Patients with BRAF mutation were excluded. Patients were classified according to treatment (rego- or TFD/TPI-treated) and RAS mutational status (wild-type [WT], KRAS codon 12 mutations, KRAS codon 13 mutations, KRAS rare mutations and NRAS mutations, KRAS G12C mutation and KRAS G12D mutation).
Results: Overall, 582 patients were included in the present analysis. Overall survival did not significantly differ in rego-treated patients according to RAS extended analysis, although a trend toward a better median survival in patients carrying G12D mutation (12.0 months), Codon 13 mutation (8.0 months), and Codon 12 mutation (7.0 months) has been observed, when compared with WT patients (6.0 months). Overall survival did not significantly differ in TFD/TPI-treated patients according to RAS extended analysis, although a trend toward a better median survival in WT patients had been observed (9.0 months) in comparison with the entire population (7.0 months). Patients receiving both drugs displayed a longer survival when compared with the population of patients receiving rego alone (p = 0.005) as well as the population receiving TFD/TPI alone (p < 0.001), suggesting a group enriched for favorable prognostic factors. However, when each group was analyzed separately, the addition of TFD/TPI therapy to the rego-treated group improved survival only in all-RAS WT patients (p = 0.003). Differently, the addition of rego therapy to TFD/TPI-treated patients significantly improved OS in the Codon 12 group (p = 0.0004), G12D group (p = 0.003), and the rare mutations group (p = 0.02), in addition to all-RAS WT patients (p = 0.002). The rego-TFD/TPI sequence, compared with the reverse sequence, significantly improved OS only in the KRAS codon 12 group (p = 0.003).
Conclusions: Our data demonstrate that RAS mutations do not affect outcome in rego-treated patients as well as TFD/TPI-treated patients. Nevertheless, a trend toward a higher efficacy of rego in RAS-mutated (in particular codon 12, rare RAS mutations, and G12D) patients has been recorded. The rego-TFD/TPI sequence seems to be superior to the reverse sequence in patients carrying an RAS codon 12 mutation, although the impact of other factors as disease burden or performance status cannot be excluded.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: