Mayo Clinic, Rochester, MN
Frank A. Sinicrope , Lucas J. Huebner , Pierre Laurent-Puig , Thomas C. Smyrk , Josep Tabernero , Enrico Mini , Richard M. Goldberg , Gunnar Folprecht , Aziz Zaanan , Karine Le Malicot , Qian Shi , Steven R Alberts , Julien Taieb
Background: Duration of adjuvant FOLFOX or CAPOX for stage III CC is being guided by pt stratification into low (T1-3N1) and high (T4 or N2) risk groups based on the IDEA study. We determined the relative contributions of clinical and molecular features for prediction of time-to-recurrence (TTR) and survival after recurrence (SAR) within each risk group. Methods: Stage III CC (N=5,430) from 2 trials of adjuvant FOLFOX ± cetuximab with similar outcome by study arm [NCCTG N0147 (Alliance), PETACC-8] were used. Tumors were analyzed for mismatch repair (dMMR vs pMMR), mutations in KRAS (exon 2) and BRAFV600E. Median pt follow-up was 83.4 months. Relative contributions to predicting outcome were assessed using χ2 (Harrell’s rms) based on multivariable (MV) Cox models. Results: N (50.8%) and T (31.8%) stage were the top two contributors to prediction of TTR which supports risk grouping. High risk (n=2566) vs low risk (n=2774) pts had poorer TTR (HR 2.7, 95% CI, 2.4-3.0) and SAR [HR 1.6 (1.4-1.9)], both p<.0001. TTR: KRAS contributed the most to predicting TTR among high (58.6%) and low (51.1%) risk pts (Table). Contribution of MMR (16%) to predicting TTR was limited to low risk pts. Contribution of BRAFV600E to TTR was nearly 3-fold increased in high vs low risk pts. SAR: BRAFV600E contributed the most to predicting SAR, especially in high vs low risk pts (2-fold increase). Tumor sidedness and performance status (PS) were key contributors to SAR, but not TTR. MV associations: TTR: low risk, KRAS [HR 1.7 (1.4-2.3], MMR [HR 0.55 (.35-.87), gender (M/F) [HR 1.3 (1.0-1.5)], all p<.04]; high risk: BRAF [HR 1.3 (1.1-1.7)], sidedness (R vs L) [HR 1.14 (1.0-1.3)], KRAS [HR 1.4 (1.2-1.6)], all p<.04]. SAR: BRAF, sidedness, PS (all p<.05). Conclusions:KRAS mutation was the strongest predictor of shorter TTR in both risk groups whereas BRAFV600E was the primary driver of SAR, especially in high risk pts. Support: U10CA180821, U10CA180882, U24CA196171; BMS, Pfizer, Sanofi. NCT00079274.
Low Risk (T1-3N1) | High Risk (T4 or N2) | |||
---|---|---|---|---|
TTR | SAR | TTR | SAR | |
BRAF | 6.7% | 26.1% | 18.5% | 54.5% |
KRAS | 58.6 | 2.7 | 51.1 | 4.9 |
MMR | 15.8 | 2.0 | 1.6 | 0.2 |
Sidedness | .04 | 30.7 | 8.2 | 34.0 |
Gender | 11.7 | 0.2 | 0.9 | 1.1 |
Age | 0.2 | 8.2 | 4.1 | 0.4 |
PS | 7.0 | 30.1 | 15.5 | 7.0 |
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Abstract Disclosures
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First Author: Rona Yaeger
2024 ASCO Annual Meeting
First Author: Ingrid A. Franken
2015 ASCO Annual Meeting
First Author: Aziz Zaanan
2020 ASCO Virtual Scientific Program
First Author: Zehua Wu