Maintenance treatment with cetuximab versus observation in RAS wildtype mCRC

Presented by

Dr Valérie Boige, Institut Gustave Roussy, France

Conference

ASCO GI 2021

Trial

Phase 2, PRODIGE 28-time UNICANCER

Cetuximab was studied as a maintenance therapy in metastatic colorectal cancer (mCRC) patients during chemotherapy-free intervals in the randomised phase 2 PRODIGE 28-time UNICANCER study. Compared with observation only, treatment with cetuximab did not lead to a significantly higher 6-month progression-free survival (PFS) rate. However, PFS time was clinically meaningful improved.

Although anti-EGFR agents are active as single-therapy in RAS wildtype mCRC, only few studies are available on their role in maintenance therapy during chemotherapy-free intervals. Compared to observation, maintenance therapy with fluoropyrimidine ± bevacizumab showed significant improvement in PFS but not in overall survival (OS) in patients with unresectable mCRC and disease control after first-line doublet chemotherapy ± bevacizumab [1]. The aim of the presented multicentre, non-comparative phase 2 trial study (NCT02404935) was to compare maintenance treatment with bi-weekly cetuximab alone (arm A) or observation only (arm B) until disease progression, unacceptable toxicity, or death [2].

A total of 214 RAS wildtype unresectable mCRC patients with controlled disease after FOLFIRI + cetuximab (8 cycles) were enrolled, of which 139 were randomised (n=67 arm A, n=72 arm B). Randomisation was stratified according to tumour response, centre, baseline Köhne Score, CEA, and platelet count. In case of tumour progression during the chemotherapy-free interval, FOLFIRI + cetuximab was reintroduced for 8 cycles, followed by a new chemotherapy-free interval. Tumour response was assessed per RECIST 1.1 every 8 weeks. The primary endpoint was 6-month PFS after initiation of maintenance therapy. Secondary endpoints were overall response rate (ORR), time to strategy failure, PFS, OS, safety, quality of life, circulating tumour cells and circulating tumour DNA detection, and dynamic changes during treatment. Of the secondary endpoints, only PFS was presented.

The median follow-up was 30 months. The 6-month PFS rate was 34.3% (95% CI 23.2-46.9) in arm A and 6.9% (95% CI 2.3-15.5) in arm B. Although showing a large difference in PFS, the study did not meet its primary endpoint according to the power calculation. Evaluation of PFS as a secondary endpoint showed a median PFS during the first chemotherapy-free interval of 5.3 months in arm A and 2 months in arm B without overlap of 95% CI (see Figure).

Figure: PFS after randomisation [2]

Dr Valérie Boige (Institut Gustave Roussy, France) concluded: “Based on the study hypothesis, the cetuximab maintenance arm did not meet the primary objective. However, the clinically meaningful difference in PFS without any overlap in the confidence intervals between both arms warrants further investigation.”

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