Table 1.
Trials investigating re-challenge strategies either with or without ctDNA guidance.
| First author | Trial design | Patient sample | Outcome |
|---|---|---|---|
| A. non ctDNA guided | |||
| Schulz et al. ( 149) | Retrospective | 21pts1 anti-EGFR free therapy | Rechallenge mPFS: 3,68month (m) mOS: 52,4m |
| Parseghian et al. ( 150) | Retrospective cohort | 80pts 5,1month (m) anti-EGFR free interval |
ORR: 23% mPFS: 3,1m PFS and ORR higher depending on time interval |
| Santini et al. ( 151) | Retrospective single arm, multicentre | 39pts 6m anti-EGFR free interval |
ORR 53% PFS: 6,6m |
| Liu et al. ( 152) | Retrospective analysis of phase I/II trials | 89pts 4,5m anti-EGFR free interval |
mPFS: 4,9m; responders 1st line |
| Rossini et al. ( 153) | Retrospective real world, multicentre | 86pts. | ORR: 19,8% mPFS: 3,8m mOS: 10,2m efficacy outcome assoc. with anti-EGFR free interval and lines of therapy |
|
Tsuji,
JACCRO CC-09 trial (154) |
Prospective, multicentre phase II | 25pts | ORR: 8,3% Efficacy dependent of anti-EGFR free interval (EFI) long EFI (1y) vs short EFI mPFS: 4,4m vs 2,5m mOS: 15,8m vs. 7,3m |
| Tanioka et al. (155) | Retrospective | 14pts 13,1m interval |
ORR: 3% mPFS: 4,2m |
| Chong et al. (156) | Retrospective | 22pts 13,5m interval |
DCR: 45,4% mPFS: 4,1m mOS: 7,7m |
| Karani et al. (157) | Retrospective | 17pts 1-2 lines of intervening therapy |
ORR: 18% mPFS: 3,3m mOS: 8,4m |
|
Masuishi et al.
JACCRO CC-08 trial (158) |
Retrospective | 34pts | Efficacy dependent of anti-EGFR free interval (EFI) long EFI (1y) vs short EFI mPFS: 4,6m vs. 2,1m mOS: 14,6m vs. 6,3m |
| B. ctDNA guided | |||
|
Martinelli et al.-
CAVE trial (159) |
Prospective, phase II trial | Interval>4m, 48pts ctDNA-WT: RAS/BRAF/EGFR-S492R 19pts ctDNA-MT |
ctDNA-WT: mPFS: 4,1m; mOS: 17,3m ctDNA-MT: mPFS: 3m; mOS: 10,4m |
| Mariani et al. (160) | Multicentre, retrospective | 26pts ctDNA WT: RAS/BRAF before rechallenge |
ORR 25% mPFS: 3,5m mOS: 5m efficacy dependent on prev. response to EGFR inhibition, anti-EGFR free interval, previous lines of therapies. |
| Cremolini et al.- CRICKET trial (161) | Multicentre, phase II trial | 13pts RAS-WT ctDNA 12pts RAS-MT ctDNA ctDNA RAS/BRAF status before rechallenge 4m interval at least |
RAS ctDNA-WT vs ctDNA-MT ORR: 31% vs 0% mPFS: 4m vs 1,9m mOS: 12.5m vs 5,2m |
| Sunakawa et al. (162) | Retrospective | 10pts RAS-WT ctDNA 6pts RAS-MT ctDNA ctDNA guided analysis of JACCRO CC-08/-09 |
RAS ctDNA-WT vs RAS ctDNA-MT DCR: 80% vs 33,3% mPFS: 4,7m vs 2,3m mOS: 16m vs 3,8m |
| Sartori-Bianchi et al.- CHRONOS trial (163) | Prospective | 27pts, ctDNA-WT: RAS, BRAF, EGFR-ECD
median 11,5m interval |
ORR: 30% mPFS: 16weeks mOS: 55 weeks |