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.
Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer–related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer–related mortality.
We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.
The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).
In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.)
This PLK1-inhibitor seems extremely promising. This phase II trial studied pre-treated KRAS-mut patients with FOLFIRI + bev + study drug and the response rates and PFS were quite remarkable. Given the compelling results, they went from this study to a phase III 1L study.
Interesting study where intermittent FOLFIRI + pan was seemingly just as effective as continuous therapy. The ongoing Phase III IMPROVE-2 is the confirmatory trial and if positive could change standard practice. Of note, intermittent meant eight (8) cycles followed by a holiday until progression when it was reinitiated.
Combination beat monotherapy is another option for MSI patients. Is combo better then pembro?
Here is a large phase-III well done study confirming what we knew from earlier studies, that ipilimumab plus nivolumab (Ipi+Nivo) is highly active and effective in the microsatellite instability-high metastatic colorectal cancer (MSI-high met-CRC) population. This is most likely more effective than single agent IO therapy but with higher rates of toxicity. When all things are equal, I would consider this to be the standard of care (SOC) in this context.
This Japanese study showed no benefit with the addition of oxaliplatin to fluoropyrimidine plus bevacizumab (5FU+bev) in patients who were aged 70-74 but unfit, or >=75. Interestingly survival was actually shorter in the patients who received oxaliplatin at 21.3 vs 19.7 months.
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