If anti PD-L1 was not used as first line treatment, this study shows you can still use it as second line.
Are checkpoint inhibitors better than chemotherapy in the second-line setting for deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC)?
In this phase 2 randomized clinical trial including 122 patients, avelumab, an anti–programmed cell death ligand 1 antibody, was associated with significantly better progression-free survival and disease control duration than standard second-line treatment. In addition, avelumab had a favorable safety profile in the second-line setting of dMMR/MSI mCRC.
These findings suggest that for patients with dMMR/MSI mCRC not treated with pembrolizumab in the first-line setting, immune checkpoint inhibitors may be an option in the second-line setting, with better efficacy and tolerability than the current standard of care.
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.
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.
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.
Patients were randomized to receive standard second-line therapy or avelumab every 2 weeks until progression, unacceptable toxic effects, or patient refusal.
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).
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.
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.
ClinicalTrials.gov Identifier: NCT03186326
Overall survival (OS) improvement was not statistically significant in the study arm but is a non-chemotherapy option. Patients here had tumors with MSS.
Less maintenance is NOT NON-inferior, so it is inferior in patients with wild type BRAF metastatic colon cancer. So it is better to keep on the full regimen. Although, quality of life is better.
Colorectal cancer screening by peripheral blood testing? This cell-free DNA assay had an 83% sensitivity and 90% specificity for advanced neoplasia. However, the issue is that this does not detect precancerous lesions well. Colonoscopy has its obvious advantages as it can both diagnose colorectal cancer as well as eradicate precancerous lesions.
This is a nice, practical study showing that when considering liver directed therapy, options in metastatic CRC, CT’s alone are insufficient and contrasted MRI can be helpful. More than 30% of patients had care that was impacted using MRI prior to any therapeutic decisions.
Negative study for the use of HIPEC in the adjuvant setting of high-risk or locally advanced colorectal cancers, including those with perforation and peritoneal invasion. HIPEC doesn’t seem to reduce the risk of peritoneal recurrence after potentially curative resection.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
