Promising New Agents for Colorectal Cancer

Satya Das, Kristen K. Ciombor, Sigurdis Haraldsdottir, Richard M. Goldberg*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

37 Citations (Scopus)


Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient’s performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility. Metastasectomy may be an option for patients with a low burden of disease and accessible liver- or lung-limited metastases. In some unresectable cases, systemic therapy with a FOLFOX- or FOLFIRI-based regimen with or without a biologic agent can lead to sufficient disease reduction to make a patient eligible for resection of metastatic disease. Tumor sidedness and RAS mutational status guide which biologic we add to the initial chemotherapy backbone, with patients with left-sided, RAS wild-type (WT) tumors receiving anti-epidermal growth factor receptor (EGFR)-directed therapy and patients with right-sided tumors or those with RAS mutations receiving bevacizumab. In patients with tumors that manifest microsatellite instability or deficient mismatch repair, we typically administer checkpoint inhibitors such as pembrolizumab or nivolumab after progression on irinotecan- or oxaliplatin-based therapies. In patients with progressive disease, we routinely send tumor tissue for next generation sequencing (NGS) to assess for the presence of actionable genomic alterations such as HER2, BRAF, and TRK fusions and offer them the option of enrollment on clinical trials with agents targeting those or other identified alterations.

Original languageEnglish
Article number29
JournalCurrent Treatment Options in Oncology
Issue number6
Publication statusPublished - 1 Jun 2018

Bibliographical note

Funding Information:
Satya Das declares that he has no conflict of interest. Kristen K. Ciombor has received funding for clinical trials paid to her institution from Pfizer, Boston Biomedical, MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, and Array BioPharma, and has also received reimbursement for travel expenses from Array BioPharma. Sigurdis Haraldsdottir declares that she has no conflict of interest. Richard M. Goldberg has received research funding through a grant from Merck, and has received compensation from Merck, Merck KGA, and Taiho for service as a consultant.

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Other keywords

  • BRAF
  • HER2
  • Metastatic colorectal cancer
  • Microsatellite instability
  • RAS
  • Therapeutics


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