Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability
Authors: Taïeb Julien , Bouche Olivier , André Thierry , Le Malicot Karine , Laurent-Puig Pierre , Bez Jérémie , Toullec Clémence , Borg Christophe , Randrian Violaine , Evesque Ludovic , Corbinais Stéphane , Perrier Hervé , Buecher Bruno , Di Fiore Frederic , Gallois Claire , Emile Jean Francois , Lepage Côme , Elhajbi Farid , Tougeron David ,   SAMCO-PRODIGE 54 Investigators, THIROT-BIDAULT Anne , MINEUR Laurent , AUDEMAR Franck , HOCINE Fayçal , KIM Stefano , FEIN Francine , ALMOTLAK Hamadi , DOS SANTOS Mélanie , HARTWIG Johannes , MELIS Adrien , BOLLIET Marion , ALDABBAGH Kaïs , CHEAIB Sonia , HANS Sophie , GHIRINGHELLI François , REBISCHUNG Christine , ROTH Gaël , GRANGER Victoire , CHIBAUDEL Benoist , CARNOT Aurélien , PANNIER Diane , MARTINAGE MAKHLOUFI Samira , WALTER Thomas , DE LA FOUCHARDIERE Christelle , BASTHISTE-PELE Christelle , DULUC Muriel , GUARDIOLA Emmanuel , LINOT Benjamin , CASTANIE Hélène , LAGASSE Jean-Paul , VAILLANT Jean-Nicolas , CORIAT Romain , COHEN Romain , LOPEZ Daniel , VAFLARD Pauline , APARICIO Thomas , THAURY Juliette , KHEMISSA  AKOUZ Faiza , SMITH Denis , CHAUVENET Marion , FERRU Aurélie , PILLET Armelle , DE SINGLY Anaïs , BIDEAU Karine , BOTSEN Damien , BRASSEUR Mathilde , LIEVRE Astrid , GOUTTEBEL Marie-Claude , SEFRIOUI David , MICHEL Pierre , GANGLOFF Alice , CHAMOIS Jérôme , GASNAULT Laurent , LIGEZA POISSON Catherine , PHELIP Jean-Marc , BEN ABDELGHANI Meher , GUILLET Pierre , SIBERTIN-BLANC Camille , CAULET Morgane , LOPEZ Anthony 
Published: August 2023

Importance

Only 1 randomized clinical trial has shown the superiority of immune checkpoint inhibitors in patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC) in the first-line setting.

Objectives

To determine whether avelumab (an anti–programmed cell death ligand 1 antibody) improves progression-free survival (PFS) compared with standard second-line chemotherapy in patients with dMMR/MSI mCRC.

Design, Setting, and Participants

The SAMCO-PRODIGE 54 trial is a national open-label phase 2 randomized clinical trial that was conducted from April 24, 2018, to April 29, 2021, at 49 French sites. Patients with dMMR/MSI mCRC who experienced progression while receiving standard first-line therapy were included in the analysis.

Interventions

Patients were randomized to receive standard second-line therapy or avelumab every 2 weeks until progression, unacceptable toxic effects, or patient refusal.

Main Outcome and Measures

The primary end point was PFS according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1, evaluated by investigators in patients with mCRC and confirmed dMMR and MSI status who received at least 1 dose of treatment (modified intention-to-treat [mITT] population).

Results

A total of 122 patients were enrolled in the mITT population. Median age was 66 (IQR, 56-76) years, 65 patients (53.3%) were women, 100 (82.0%) had a right-sided tumor, and 52 (42.6%) had BRAF V600E–mutated tumors. There was no difference in patients and tumor characteristics between treatment groups. No new safety concerns in either group were detected, with fewer treatment-related adverse events of at least grade 3 in the avelumab group than in the chemotherapy group (20 [31.7%] vs 34 [53.1%]; P = .02). After a median follow-up of 33.3 (95% CI, 28.3-34.8) months, avelumab was superior to chemotherapy with or without targeted agents with respect to PFS (15 [24.6%] vs 5 [8.2%] among patients without progression; P = .03). Rates of PFS rates at 12 months were 31.2% (95% CI, 20.1%-42.9%) and 19.4% (95% CI, 10.6%-30.2%) in the avelumab and control groups, respectively, and 27.4% (95% CI, 16.8%-39.0%) and 9.1% (95% CI, 3.2%-18.8%) at 18 months. Objective response rates were similar in both groups (18 [29.5%] vs 16 [26.2%]; P = .45). Among patients with disease control, 18 (75.7%) in the avelumab group compared with 9 (19.1%) in the control group had ongoing disease control at 18 months.

Conclusions

The SAMCO-PRODIGE 54 phase 2 randomized clinical trial showed, in patients with dMMR/MSI mCRC, better PFS and disease control duration with avelumab over standard second-line treatment, with a favorable safety profile.

Trial Registration

ClinicalTrials.gov Identifier: NCT03186326