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

• Published in: ESMO open Vol. 7; no. 5; p. 100567
• Main Authors: Ciardiello, D., Chiarazzo, C., Famiglietti, V., Damato, A., Pinto, C., Zampino, M.G., Castellano, G., Gervaso, L., Zaniboni, A., Oneda, E., Rapisardi, S., Bordonaro, R., Zichi, C., De Vita, F., Di Maio, M., Parisi, A., Giampieri, R., Berardi, R., Lavacchi, D., Antonuzzo, L., Tamburini, E., Maiorano, B.A., Parrella, P., Latiano, T.P., Normanno, N., De Stefano, A., Avallone, A., Martini, G., Napolitano, S., Troiani, T., Martinelli, E., Ciardiello, F., Maiello, E.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-10-2022; Elsevier
• Subjects: chemotherapy; first line treatment; KRASG12C mutation; mCRC; Original Research; real-world data; KRASG12C mutation; first line treatment; real-world data; mCRC; chemotherapy
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2022.100567

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 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.
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).
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.
•KRASG12C mutation is rare and occurs in 3.7% of the study population.•The presence of KRASG12C mutation is correlated with an aggressive disease, with reduced response to chemotherapy.•Only 62% and 36% of patients with KRASG12C-mutant mCRC are fit to receive second or third lines of treatment, respectively.•The use of chemotherapy triplets is associated with improved outcomes compared with chemotherapy doublets.