In the Journals

Colorectal cancer subtypes could help predict best initial treatment option

Heinz-Josef Lenz, MD
Heinz-Josef Lenz

Consensus molecular subtype classification demonstrated potential clinical utility as an independent prognostic factor for patients with metastatic colorectal cancer who receive first-line therapy, according to results of a prospective phase 3 trial published in Journal of Clinical Oncology.

Results showed consensus molecular subtype (CMS) may have predictive value to help guide selection of anti-vascular endothelial growth factor (VEGF) and anti-endothelial growth factor receptor (EGFR) therapy for this patient population.

“We were happy that we were able to confirm previous data that was done on stage 2 or stage 3 patients that showed a prognostic value in metastatic disease. This is the largest cohort to date we have seen confirming this,” Heinz-Josef Lenz, MD, professor of medicine in the division of oncology at Keck School of Medicine of University of Southern California, told HemOnc Today. “What was surprising to us is that this classification was not only prognostic for PFS and OS, but that it was predictive. This gave us insight into how certain drugs may work in certain patients with colon cancer.”

The phase 3 CALGB/SWOG 80405 trial compared the addition of bevacizumab (Avastin, Genentech) or cetuximab (Erbitux, Eli Lilly) to standard modified FOLFOX or FOLFIRI as first-line treatment of advanced colorectal cancer.

Among the 1,137 patients in the primary analysis cohort, Lenz and colleagues classified CMS for 581 (mean age, 59.5 years; 64.6% men) using a NanoString (NanoString Technologies) gene expression panel. The four distinct, biologically characterized CMS subgroups included CMS1 (microsatellite instability immune, n = 104), CMS2 (canonical, n = 242), CMS3 (metabolic, n = 68) and CMS4 (mesenchymal, n = 167).

Assessing the prognostic and predictive value of the CMS subgroups served as the study’s primary endpoint.

Results showed significant prognostic value of CMS classification for OS (P < .001) and PFS (P = .001). CMS classification also appeared to be a predictive marker for both cetuximab and bevacizumab in terms of OS (P for interaction < 001) and PFS (P for interaction = .0032).

Patients in the CMS1 group demonstrated significantly longer median OS with bevacizumab vs. cetuximab (22.5 months vs. 11.7 months; P < .001) as well as longer median PFS (8.7 months vs. 5.7 months; P < .001). However, in the CMS2 group, patients demonstrated significantly longer median OS with cetuximab vs. with bevacizumab (42 months vs. 36 months; P = .0046) and longer median PFS (14.1 months vs. 13.1 months), although the PFS difference did not reach statistical significance.

Patients in the study all had KRAS wild-type tumors, leading to a significant minority of CMS3 cancers, which served as the study’s primary limitation.

“This is a very helpful tool to better understand potential, novel and more effective treatments for patients with metastatic colon cancer,” Lenz said. “The next step is to see if we can extract different signatures within these subtypes that might better target and personalize care with drugs for patients.”  by John DeRosier

For more information:

Heinz-Josef Lenz, MD, can be reached at The University of Southern California Keck School of Medicine, 1975 Zonal Ave., Los Angeles, CA 90033; email: lenz@usc.edu

Disclosures: Lenz reports honoraria from, consultant/advisory roles with, and/or travel expenses from Bayer, Boehringer Ingelheim, Merck Serono, Pfizer and Roche. Please see the study for all other authors’ relevant financial disclosures.

Heinz-Josef Lenz, MD
Heinz-Josef Lenz

Consensus molecular subtype classification demonstrated potential clinical utility as an independent prognostic factor for patients with metastatic colorectal cancer who receive first-line therapy, according to results of a prospective phase 3 trial published in Journal of Clinical Oncology.

Results showed consensus molecular subtype (CMS) may have predictive value to help guide selection of anti-vascular endothelial growth factor (VEGF) and anti-endothelial growth factor receptor (EGFR) therapy for this patient population.

“We were happy that we were able to confirm previous data that was done on stage 2 or stage 3 patients that showed a prognostic value in metastatic disease. This is the largest cohort to date we have seen confirming this,” Heinz-Josef Lenz, MD, professor of medicine in the division of oncology at Keck School of Medicine of University of Southern California, told HemOnc Today. “What was surprising to us is that this classification was not only prognostic for PFS and OS, but that it was predictive. This gave us insight into how certain drugs may work in certain patients with colon cancer.”

The phase 3 CALGB/SWOG 80405 trial compared the addition of bevacizumab (Avastin, Genentech) or cetuximab (Erbitux, Eli Lilly) to standard modified FOLFOX or FOLFIRI as first-line treatment of advanced colorectal cancer.

Among the 1,137 patients in the primary analysis cohort, Lenz and colleagues classified CMS for 581 (mean age, 59.5 years; 64.6% men) using a NanoString (NanoString Technologies) gene expression panel. The four distinct, biologically characterized CMS subgroups included CMS1 (microsatellite instability immune, n = 104), CMS2 (canonical, n = 242), CMS3 (metabolic, n = 68) and CMS4 (mesenchymal, n = 167).

Assessing the prognostic and predictive value of the CMS subgroups served as the study’s primary endpoint.

Results showed significant prognostic value of CMS classification for OS (P < .001) and PFS (P = .001). CMS classification also appeared to be a predictive marker for both cetuximab and bevacizumab in terms of OS (P for interaction < 001) and PFS (P for interaction = .0032).

Patients in the CMS1 group demonstrated significantly longer median OS with bevacizumab vs. cetuximab (22.5 months vs. 11.7 months; P < .001) as well as longer median PFS (8.7 months vs. 5.7 months; P < .001). However, in the CMS2 group, patients demonstrated significantly longer median OS with cetuximab vs. with bevacizumab (42 months vs. 36 months; P = .0046) and longer median PFS (14.1 months vs. 13.1 months), although the PFS difference did not reach statistical significance.

Patients in the study all had KRAS wild-type tumors, leading to a significant minority of CMS3 cancers, which served as the study’s primary limitation.

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“This is a very helpful tool to better understand potential, novel and more effective treatments for patients with metastatic colon cancer,” Lenz said. “The next step is to see if we can extract different signatures within these subtypes that might better target and personalize care with drugs for patients.”  by John DeRosier

For more information:

Heinz-Josef Lenz, MD, can be reached at The University of Southern California Keck School of Medicine, 1975 Zonal Ave., Los Angeles, CA 90033; email: lenz@usc.edu

Disclosures: Lenz reports honoraria from, consultant/advisory roles with, and/or travel expenses from Bayer, Boehringer Ingelheim, Merck Serono, Pfizer and Roche. Please see the study for all other authors’ relevant financial disclosures.