Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Oct;7(5):100567.
doi: 10.1016/j.esmoop.2022.100567. Epub 2022 Aug 19.

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

D Ciardiello  1 , C Chiarazzo  2 , V Famiglietti  3 , A Damato  4 , C Pinto  4 , M G Zampino  5 , G Castellano  5 , L Gervaso  5 , A Zaniboni  6 , E Oneda  6 , S Rapisardi  7 , R Bordonaro  7 , C Zichi  8 , F De Vita  8 , M Di Maio  8 , A Parisi  9 , R Giampieri  10 , R Berardi  10 , D Lavacchi  11 , L Antonuzzo  11 , E Tamburini  12 , B A Maiorano  13 , P Parrella  14 , T P Latiano  2 , N Normanno  15 , A De Stefano  16 , A Avallone  16 , G Martini  3 , S Napolitano  3 , T Troiani  3 , E Martinelli  3 , F Ciardiello  17 , F De Vita  3 , E Maiello  2
Affiliations
Multicenter Study

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

D Ciardiello et al. ESMO Open. 2022 Oct.

Abstract

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.

Keywords: KRASG12C mutation; chemotherapy; first line treatment; mCRC; real-world data.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Progression-free survival of (A) first-, (B) second- and (C) third-line therapies. CI, confidence interval; mPFS, median progression-free survival; PFS, progression-free survival.
Figure 2
Figure 2
Overall survival. CI, confidence interval; mOS: median overall survival; OS, overall survival.
Figure 3
Figure 3
(A) Median progression-free survival and (B) overall survival according to the type of first-line therapy. CI, confidence interval; CT, chemotherapy; mPFS, median progression-free survival, OS, overall survival.
See this image and copyright information in PMC

References

    1. Ciardiello F., Ciardiello D., Martini G., Napolitano S., Tabernero J., Cervantes A. Clinical management of metastatic colorectal cancer in the era of precision medicine. CA Cancer J Clin. 2022;72:372–401. - PubMed
    1. Martinelli E., Ciardiello D., Martini G., et al. Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives. Ann Oncol. 2020;31(1):30–40. - PubMed
    1. Tabernero J., Grothey A., Van Cutsem E., et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAFV600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol. 2021;39(4):273–284. - PMC - PubMed
    1. André T., Shiu K.K., Kim T.W., et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207–2218. - PubMed
    1. Lenz H.J., Van Cutsem E., Luisa Limon M., et al. First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study. J Clin Oncol. 2022;40(2):161–170. - PubMed

Publication types

MeSH terms