Table 3.
Studies evaluating circulating tumor DNA as a screening tool to detect patients who could benefit from anti-EGFR re-challenge in metastatic colorectal cancer.
| Reference/ NCT |
Type of Study |
Status | Detection Technique | Mutations Analyzed | Primary Outcoume | Secondary Outcomes |
Number of Patients Evaluated | Mutational Status at Rechallenge - Number (%) |
Number of Previous Treatment Line(s) | PFS (Months) According to Mutational ctDNA Status | HR; p-Value |
||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Wt | Mutated | Wt | Mutated | ||||||||||
| Cremolini et al. [153] | Multicenter phase II single arm |
Achieved | ddPCR | RAS | ORR | PFS and OS |
25 | 13 (52%) | 12 (48%) | 2 | 4.0 | 1.9 | HR = 0.44; p = 0.03 |
| Sartore-Bianchi et al. [155] | Multicenter interventional phase II | Achieved | ddPCR | RAS, BRAF, EGFR | ORR | PFS and OS |
52 | 36 (69%) | 26 (31%) | 2–6 | 4.0 | Not treatead by anti-EGFR | NA |
| Nakamura et al. [154] | Multicenter phase II single arm | Achieved | dPCR |
KRAS, NRAS, BRAF,
PIK3CA, EGFR S492R |
RR | PFS, OS, aEFI |
33 | NA | NA | NA | 7.0 | 2,9 | NA |
| NCT-03259009 (RASINTRO) | Prospective observational cohort | Recruitment achieved | NGS | RAS | PFS | Tumor response and OS |
73 (estimated) |
- | - | - | - | - | - |
| NCT-04509635 | Single center Prospective interventional randomized | Not yet recruiting |
NA | RAS | DCR | ORR, PFS and OS |
50 (estimated) |
- | - | - | - | - | - |
| NCT-04775862 | Prospective phase II | Recruiting | NA | RAS | ORR, PFS |
Proportion of RAS wt patients after 2nd progression and prevalence of RAS G12C mutation | 60 (estimated) |
- | - | - | - | - | - |
aEFI: anti-EGFR antibody free interval; CI: Confidence interval; ctDNA: circulating tumor DNA; DCR: disease control rate; ddPCR: digital droplet PCR; HR: hazard ratio; NA: Not available; NGS: New Generation Sequencing; ORR: Objective response rate; OS: Overall survival; OS1: Overall survival after first line of treatment; PCR: polymerase chain reaction; PFS: Progression free survival; RR: response rate; wt: wild type.