[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.204.176.125. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 795
Citations 0
Research Letter
April 23, 2020

Central Nervous System as Possible Site of Relapse in ERBB2-Positive Metastatic Colorectal Cancer: Long-term Results of Treatment With Trastuzumab and Lapatinib

Author Affiliations
  • 1Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
  • 2Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milan, Italy
  • 3Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
  • 4Istituto di Candiolo, Fondazione del Piemonte per l’Oncologia, IRCCS, Candiolo, Italy
  • 5Dipartimento di Oncologia, Università degli Studi di Torino, Turin, Italy
  • 6Università della Campania “L. Vanvitelli”, Naples, Italy
  • 7Precision Oncology, IFOM-FIRC Institute of Molecular Oncology, Milan, Italy
JAMA Oncol. Published online April 23, 2020. doi:10.1001/jamaoncol.2020.0571

In colorectal cancer, ERBB2 amplification occurs in 5% of RAS wild-type metastatic tumors.1 In the pivotal HERACLES-A trial, chemorefractory patients with ERBB2 (formerly HER2)-positive metastatic colorectal cancer (mCRC) were treated with the combination of trastuzumab and lapatinib,2 demonstrating the proof of concept that the dual ERBB2 blockade previously found actionable in preclinical models3 could be successfully translated to the clinic with remarkable clinical benefit. We also reported that ERBB2 copy number in plasma was associated with that detected in tumor tissue, identified a cutoff value associated with clinical response,4 and studied acquired resistance on therapeutic ERBB2 blockade by longitudinal monitoring of circulating tumor DNA. Along this line, we documented that the onset of resistance was associated with emerging KRAS variant clones, BRAF amplification, and other molecular alterations already known in breast cancer, such as those of ERBB2, EGFR, PIK3CA, and PTEN.5

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×