Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Year in Review
  • Published:

Colorectal cancer in 2023

New options for late-line treatment of metastatic colorectal cancer

Nature Reviews Gastroenterology & Hepatology volume 21, pages 76–77 (2024)Cite this article

Subjects

Metastatic colorectal cancer is a heterogeneous disease associated with poor patient outcomes. Although the past decade has seen few first-line treatment advances, key studies published in 2023 established new options for late-line therapy of the disease with and without oncogenic drivers, thus expanding the continuum of care in metastatic colorectal cancer.

Key advances

  • In the SUNLIGHT trial, the addition of bevacizumab to third-line trifluridine–tipiracil (FTD/TPI) resulted in longer overall survival independent from previous exposure to VEGF inhibitors in patients with metastatic colorectal cancer (mCRC)4.

  • The FRESCO-2 study established fruquintinib as a new option for late-line treatment in patients with mCRC after failure of standard therapies including FTD/TPI and/or regorafenib5.

  • In the CodeBreaK 300 trial, the KRAS-G12C inhibitor sotorasib combined with panitumumab was superior to either FTD/TPI or regorafenib in a population of patients with pretreated KRASG12C-mutated mCRC10.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Late-line treatment algorithm in metastatic colorectal cancer.

References

  1. Cervantes, A. et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 34, 10–32 (2023).

    Article  CAS  PubMed  Google Scholar 

  2. Grothey, A. et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381, 303–312 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Mayer, R. J. et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N. Engl. J. Med. 372, 1909–1919 (2015).

    Article  PubMed  Google Scholar 

  4. Prager, G. W. et al. Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N. Engl. J. Med. 388, 1657–1667 (2023).

    Article  CAS  PubMed  Google Scholar 

  5. Dasari, A. et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet 402, 41–53 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. Kopetz, S. et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N. Engl. J. Med. 381, 1632–1643 (2019).

    Article  CAS  PubMed  Google Scholar 

  7. Yaeger, R. et al. Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C. N. Engl. J. Med. 388, 44–54 (2023).

    Article  CAS  PubMed  Google Scholar 

  8. Strickler, J. H. et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 24, 496–508 (2023).

    Article  CAS  PubMed  Google Scholar 

  9. Sartore-Bianchi, A. et al. Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial. Nat. Med. 28, 1612–1618 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fakih, M. G. et al. Sotorasib plus panitumumab in refractory colorectal cancer with mutated KRAS G12C. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2308795 (2023).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Oncology Department, Veneto Institute of Oncology IOV–IRCCS, Padua, Italy

    Sara Lonardi

  2. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Filippo Pietrantonio

Authors
  1. Sara Lonardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Filippo Pietrantonio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sara Lonardi.

Ethics declarations

Competing interests

S.L. reports research funding (to institution) from Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daichii Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche and Servier; personal honoraria as an invited speaker from Amgen, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre-Fabre, Roche and Servier; and participation in advisory board for Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier and Takeda. F.P. reports research funding (to institution) from Lilly, BMS, AstraZeneca, Incyte, Amgen and Agenus; personal honoraria as an invited speaker from Amgen, Merck-Serono, BMS, Servier, Bayer, Pierre-Fabre, Takeda, Ipsen and Astellas; and participation in advisory board for Amgen, Merck-Serono, MSD, Bayer, Organon, Astellas, Takeda, Servier and GSK.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lonardi, S., Pietrantonio, F. New options for late-line treatment of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol 21, 76–77 (2024). https://doi.org/10.1038/s41575-023-00881-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-023-00881-1

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing