Feb 26, 2018
By Caroline Hopkins, ASCO Publishing
At the 2018 Gastrointestinal (GI) Cancers Symposium, Thierry Andre, MD, of Saint-Antoine Hospital, France, presented updated results from CheckMate-142, a phase II clinical trial investigating the effect of nivolumab plus ipilimumab in patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC). The results were simultaneously published online in the Journal of Clinical Oncology (JCO).
In the JCO article, lead author Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, reported that the addition of ipilimumab to nivolumab monotherapy resulted in high response rates, durable clinical benefits, manageable safety, and improved patient-reported outcomes (PROs). The combination, which demonstrated increased efficacy over anti–programmed death-1 (anti-PD1) monotherapy, may point to a new standard of care in treating patients with dMMR/MSI-H mCRC. Dr. Overman shared additional perspective on the study with ASCO Connection.
CheckMate-142 has the potential to affect standard of care for dMMR/MSI-H mCRC. Since publishing the results, have you seen clinicians make changes to treatment decisions?
MO: The recent U.S. Food and Drug Administration (FDA) approvals for both pembrolizumab and nivolumab for dMMR/MSI-H CRC have led to remarkable changes in practice as testing for dMMR has become a standard part of molecular testing for mCRC. In part, the great outcomes from anti-PD1 in dMMR/MSI-high mCRC have strongly supported the effort to find these rare patients through testing all CRC for dMMR.
How do you expect these latest results will impact treatment in this patient population going forward?
MO: The results presented at the GI Cancers Symposium demonstrate the durability of benefit from nivolumab monotherapy in dMMR/MSI-high mCRC, with nearly 50% of patients remaining progression-free after 2 years of therapy.
Were the results surprising? Did you expect nivolumab plus ipilimumab would yield the results it did?
MO: The expectation was for an improvement with combination therapy, but given the uncertainty regarding the resistance mechanisms at play for anti-PD1 therapy in dMMR/MSI-high CRC, the amount of improvement was unknown. In the end, this combination provides a novel treatment approach that is worth further study and demonstrates that further optimization beyond single-agent anti-PD1 therapy for this rare tumor subset can be successful and can lead to improved outcomes.
The updated CheckMate-142 results were presented at the 2018 GI Cancers Symposium in January. What is the added value of simultaneously publishing those results in a journal?
MO: Simultaneous publication improves research transparency. In addition to the results presented at the meeting, a peer-reviewed and more complete representation of the data is provided in the journal article. Thus, a more comprehensive presentation of the data is now available to the greater oncology community and the public rather than just to the symposium attendees.
With the practice-changing research presented at ASCO-sponsored and -cosponsored oncology conferences throughout the year, it has long been a hope among authors that their corresponding articles might be published online at the very moment they’re presented to meeting attendees.
JCO is pleased to now offer this opportunity for high-profile or practice-changing research. Interested authors should send a presubmission inquiry to firstname.lastname@example.org, along with a cover letter that describes the work in sufficient detail to determine suitability for simultaneous publication.