KEY TAKEAWAYS
- The phase II AVETRIC trial assessed the efficacy and safety of first-line mFOLFOXIRI plus cet and ave in RAS wt mCRC pts.
- The study’s primary endpoint was PFS.
- mFOLFOXIRI plus Cet and Ave showed promising results in terms of PFS and response rate in pMMR RAS and BRAF wt mCRC pts.
The modified schedule of FOLFOXIRI (mFOLFOXIRI) in combination with an anti-EGFR agent has shown promising results in managing the safety profile and activity in RAS wild-type (wt) metastatic colorectal cancer (mCRC). The AVETRIC study investigated the efficacy and safety of first-line mFOLFOXIRI in combination with cet and avelumab (ave) in RAS wt mCRC patients (pts).
The AVETRIC study is a phase II, multicenter, single-arm trial designed to explore the efficacy and safety of mFOLFOXIRI in combination with cetuximab and avelumab as first-line treatment for RAS wild-type mCRC pts.
The trial involved administering mFOLFOXIRI plus cetuximab and avelumab to unresectable and previously untreated RAS wt mCRC pts every 2 weeks for up to 12 cycles followed by maintenance treatment until disease progression. A safety run-in phase was conducted with the first 6 enrolled pts due to the occurrence of grade 3-4 diarrhea in 2 (33%) pts, which prompted a reduction in the irinotecan dose to 130 mg/sqm.
The primary endpoint was Progression Free Survival (PFS), with 58 pts needed to detect an increase in median PFS from 10.0 to 19.4 months (mos), setting one-sided α and β errors at 0.05 and 0.10, respectively.
Between June 2020 and December 2021, 62 pts were enrolled in 16 Italian centers for a study. The main characteristics of the pts were as follows: the median age of 56 years, ECOG PS 0 of 87%, synchronous metastases of 94%, liver-only disease of 42%, and left-sided primary tumor of 89%. All pts had BRAF wild-type and proficient MMR (pMMR) tumors. The primary endpoint was successfully met.
At a median follow-up of 16.0 months, 39 (63%) events were recorded, and the median progression-free survival (mPFS) was 14.1 months (90% CI 12.0-16.7, Brookmeyer-Crowley test p < 0.001). The response rate and disease control rate were 82% and 98%, respectively, and the R0 resection rate was 21% (27% in the liver-only subgroup).
Early tumor shrinkage was achieved in 74% of pts, and the median deepness of response was 56%. For pts treated after the study amendment (n=56), the main grade 3-4 adverse events were neutropenia (27%), diarrhea (27%), skin rash (14%), asthenia (14%), nausea (11%), stomatitis (7%), and febrile neutropenia (2%). Grade 3-4 immune-related adverse events were reported in 6% of pts. Overall survival results were immature.
The AVETRIC study was successful in meeting its primary endpoint. The combination of mFOLFOXIRI plus cet and ave has achieved promising results regarding PFS and the response rate for pts with pMMR RAS and BRAF wt mCRC. It’s good to know that translational analyses are being conducted to evaluate the impact of immune-related biomarkers.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00641-5/fulltext
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04513951
Conca, V., Antoniotti, C., Bergamo, F., Pietrantonio, F., Rossini, D., Scartozzi, M., Perissinotto, E., Leone, A., Pusceddu, V., Borelli, B., Cavanna, L., Latiano, T., Santini, D., Masi, G., Salvatore, L., Frassineti, G., Leone, F., Tamberi, S., Boni, L., Cremolini, C. SO-27 Modified FOLFOXIRI plus cetuximab and avelumab as initial therapy in RAS wild-type unresectable metastatic colorectal cancer: Results of the phase II AVETRIC trial by GONO. https://doi.org/10.1016/j.annonc.2023.04.499
