Clinical efficacy of sequential treatments in KRASG12C -mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM)

ESMO Open

article

D. Ciardiello¹  C. Chiarazzo¹  V. Famiglietti²  A. Damato³  C. Pinto³  M.G. Zampino⁴  G. Castellano⁴  L. Gervaso⁴  A. Zaniboni⁵  E. Oneda⁵  S. Rapisardi⁶  R. Bordonaro⁶  C. Zichi⁷  F. De Vita⁷  M. Di Maio⁷  A. Parisi⁸  R. Giampieri⁹  R. Berardi⁹  D. Lavacchi^1,10  L. Antonuzzo^1,10  E. Tamburini^1,11  B.A. Maiorano¹  P. Parrella^1,13  T.P. Latiano¹  N. Normanno^1,14  A. De Stefano^1,15  A. Avallone^1,15  G. Martini²  S. Napolitano²  T. Troiani²  E. Martinelli²  F. Ciardiello²  F. De Vita²  E. Maiello¹ 

[1] Oncology Unit, IRCCS Foundation Casa Sollievo della Sofferenza;Medical Oncology Unit, Department of Precision Medicine, “Luigi Vanvitelli” University of Campania;Medical Oncology Unit, Comprhensive Cancer Center;Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico;Medical Oncology Unit, Poliambulanza Foundation;Medical Oncology Unit;Department of Oncology, University of Turin;Department of Life, Health and Environmental Sciences, University of L’Aquila;Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona;Clinical Oncology Unit, Department of Experimental and Clinical Medicine, University of Florence;Oncology Department and Palliative Care, Cardinale Panico, Tricase City Hospital;Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart;Oncology Laboratory, Foundation Casa Sollievo della Sofferenza IRCCS;Cellular Biology and Biotherapy, Istituto Nazionale Tumori;Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori

关键词: mCRC;    KRASG12C mutation;    chemotherapy;    first line treatment;    real-world data;   

DOI  :  10.1016/j.esmoop.2022.100567

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units.Patients and methods Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out.Results A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months).Conclusion Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

【 授权许可】

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