mFOLFOXIRI/Cetuximab Combo Improves Depth of Response in RAS Wild-Type mCRC

Akihito Tsuji, MD, PhD

Cetuximab (Erbitux) added to mFOLFOXIRI induced superior depth of response (DpR) than mFOLFOXIRI plus bevacizumab (Avastin) in treatment-naïve patients with RAS wild-type metastatic colorectal cancer (mCRC), according to results presented during the 2021 ASCO Annual Meeting.¹

Investigators in the DEEPER trial (JACCRO CC-13; UMIN000018217) sought to show that cetuximab induced a median depth of response (DpR) more than 12.5% greater than bevacizumab, with a power of 85% at a significance level of 0.05. They found that DpR was 57.4% in the cetuximab arm versus 46.0% in the bevacizumab arm, meeting the primary endpoint (P = .001). Cetuximab induced superior median DpR in both left-sided (60.3% vs 46.1%; P = .0007) and right-sided (50.0% vs 41.2%; P = .466) tumors.

“We analyzed the data according to tumor location. In left-side tumors, the DpR was much better in the cetuximab arm,” said lead author Akihito Tsuji, MD, PhD, a professor of medicine at Japan’s Kagawa University. “On the other hand, in the right-sided tumors, there was no significant difference in DpR between the two arms.”

Tsuji and his colleagues compared mFOLFOXIRI (oxaliplatin, irinotecan, folinic acid, and 5-fluorouracil) plus cetuximab (n = 173) or bevacizumab (n = 175). A total of 158 patients in the cetuximab group and 162 in the bevacizumab group were evaluable for DpR. A total of 359 patients were enrolled between July 2015 and June 2019. Data cut off was January 2021.

Tsuji said there was no statistically significant difference for early tumor shrinkage (ETS) rate and overall response rate (ORR) between the treatment groups. The ETS rate was 77.8% in the cetuximab arm compared with 74.6% in the bevacizumab arm (P = 0.479). The ORR was 69.1% for cetuximab versus 71.7% for bevacizumab (P = .604). However, 6.3% of patients in the cetuximab arm had complete response compared with 2.3% for bevacizumab.

Survival data were immature, but progression-free survival was 12.7 months (95% CI, 11.5-14.0) in both arms and overall survival was 37.6 months (95% CI, 30.8-43.0) in both arms.

The most common grade 3 or higher adverse event (AE) in the cetuximab group was neutropenia (54.9%), followed by hypertension (16.6%) and diarrhea and rash (12.0%) each. With bevacizumab, the most common grade 3 or higher AE was neutropenia (54.5%), followed by hypertension (30.1%), and anorexia and febrile neutropenia (10.8% each).

In safety data previously reported at the 2021 ASCO Gastrointestinal Cancer Symposium, 25.7% in the bevacizumab arm, of patients experienced severe AEs compared with 25.4% in the cetuximab arm. However, there were 2 (1.2%) deaths in the cetuximab arm and none with bevacizumab.²

References

1. Tsuji A, Ohori H, Yamaguchi T, et al. The randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13). J Clin Oncol. 2021,39(suppl 15): abstr 3501. doi:10.1200/JCO.2021.39.15_suppl.3501
2. Watanabe T, Tsuji A, Shiozawa M, et al. Safety analysis of the randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13). J Clin Oncol. 2021,39(suppl 3): abstr 86. doi:10.1200/JCO.2021.39.3_suppl.86