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Published on: March 14, 2019
Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite
Julien Taïeb1,2,3, Olivier Bouche4, Thierry André5
1Institut du Cancer Paris Cancer Research for Personalized Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.
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.
Insights
Avelumab demonstrated superior progression-free survival (PFS) compared to standard chemotherapy in patients with deficient mismatch repair/microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC). This immune checkpoint inhibitor offers a favorable safety profile for second-line treatment.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Oncology
Background:
- Metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) or microsatellite instability (MSI) has limited treatment options.
- Immune checkpoint inhibitors (ICIs) have shown promise, but evidence in the second-line setting for dMMR/MSI mCRC is still evolving.
Purpose of the Study:
- To evaluate the efficacy of avelumab, an anti-programmed cell death ligand 1 antibody, versus standard chemotherapy in improving progression-free survival (PFS) for patients with dMMR/MSI mCRC.
- To assess the safety and tolerability of avelumab in this patient population.
Main Methods:
- The SAMCO-PRODIGE 54 trial was a national, open-label, phase 2 randomized clinical trial involving 122 patients with dMMR/MSI mCRC who progressed on first-line therapy.
- Patients were randomized to receive either avelumab or standard second-line chemotherapy.
- Progression-free survival (PFS) was the primary endpoint, assessed by RECIST v1.1.
Main Results:
- Avelumab showed a statistically significant improvement in PFS compared to chemotherapy (P=0.03).
- Disease control was maintained longer in the avelumab group (75.7% at 18 months vs. 19.1% in the control group).
- Avelumab exhibited a more favorable safety profile, with significantly fewer treatment-related adverse events of at least grade 3 (31.7% vs. 53.1%).
Conclusions:
- Avelumab is superior to standard second-line chemotherapy in patients with dMMR/MSI mCRC, offering improved PFS and disease control duration.
- Avelumab presents a favorable safety profile, making it a viable treatment option for this specific subgroup of colorectal cancer patients.
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