Early tumor shrinkage after cetuximab predicts survival in metastatic colorectal cancer

Early tumor shrinkage after treatment with chemotherapy plus cetuximab predicted improved survival in patients with KRAS wild-type,chemorefractory metastatic colorectal cancer, according to a study review.

Researchers evaluated data from 1,289 patients who participated in the Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) and Oxaliplatin and Cetuximab in First-Line Treatment of Metastatic Colorectal Cancer (OPUS) trials between 2004 and 2006.

Overall, among patients with KRAS wild-type metastatic colorectal cancer (mCRC), researchers reported increased time-dependent c-index values for PFS and OS (P<.001) in those assigned to chemotherapy plus cetuximab (Erbitux, Eli Lilly) compared with those assigned to chemotherapy alone.

In the CRYSTAL study, patients with KRAS wild-type mCRC who received chemotherapy plus cetuximab and experienced 20% or more early tumor shrinkage at 8 weeks experienced significantly longer median PFS (14.1 months vs. 7.3 months; HR=.32; P<.001) and median OS (30 months vs. 18.6 months; HR=0.53; P<.001) than those who did not reach that tumor shrinkage benchmark.

Researchers observed the same PFS advantage (11.9 months vs. 5.7 months; HR=.22; P<.001) and OS advantage (26 months vs. 15.7 months; HR=.43; P=.006) in the OPUS study.

Geoffrey R. Oxnard

In an accompanying editorial, Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute and Brigham and Women’s Hospital, and Lawrence H. Schwartz, MD, of Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, wrote that criteria used to assess disease response may be changing.

“We propose that, for biomarker discovery, a biology-based response threshold like the one proposed by Piessevaux et al may be preferable to RECIST for separating tumors into sensitive and insensitive population,” Oxnard and Schwartz wrote. “This work represents the beginning of a period in which, for those therapies without adequate predictive tissue biomarkers, response phenotype plays an increasing role in guiding our delivery of targeted therapies.”

For more information:

Disclosure: The researchers report research funding or honoraria from, employment or leadership positions with, consultant or advisory roles with, and stock ownership in IDDI, Merck KGaA and Merck Serono.