Abstract 434P
Background
Chemotherapy combined with either VEGF or EGFR targeting mAbs improves survival of patients (pts) with mCRC. In clinical practice, the selection of antibody may take into account multiple factors, including RAS/BRAF mutation status and tumour sidedness.
Methods
IPD from 2 randomized first-line trials with head-to-head comparison of chemo+EGFRmAb v chemo+VEGFmAb in mCRC were pooled. Biomarker subpopulations (see table) were analysed. Overall survival (OS) and progression-free survival (PFS) were compared between groups by Cox model, stratified by studies and adjusted by age, gender and performance status. Treatment effects were estimated by adjusted hazard ratio (HRadj) and 95% confidence interval (CI). Within each biomarker subset, mAb efficacy was explored according to type of chemo, gender, sidedness and site of metastasis. Interaction tests were performed. P-values < 0.01 were considered statistically significant to account for multiple comparisons.
Results
1967 pts from 2 studies with data available for ≥ 1 biomarker were analysed. For the KRAS and NRAS MT groups, PFS favoured VEGF targeting (median 12.0 v 8.0 mos in KRAS MT, median 12.9 v 8.1 mos in NRAS MT), but OS did not differ significantly (see table). No difference in PFS or OS was observed in the BRAF MT or triple WT groups. Exploratory analyses of sidedness demonstrated inferior survival with EGFR mAbs (vs. VEGFmAb) in triple WT tumors on the right side of the colon (OS: HRadj 1.61, p=.056, pinteraction .099; PFS: HRadj 2.39, p=.0007, pinteraction .041). Table: 434P
| N of Trials (N of pts) | OS HRadj (95% CI) | p | PFS HRadj (95% CI) | p | |
| KRAS MT | 1 (314) | 1.08 (0.85-1.36) | 0.5396 | 1.38 (1.10-1.74) | 0.0061 |
| NRAS MT | 2 (109) | 0.76 (0.48-1.19) | 0.2340 | 1.61 (1.01-2.55) | 0.0419 |
| BRAF MT | 2 (138) | 1.01 (0.69-1.48) | 0.9488 | 1.19 (0.84-1.70) | 0.3324 |
| Triple WT | 2 (613) | 0.93 (0.78-1.11) | 0.4077 | 1.07 (0.91-1.27) | 0.3987 |
Conclusions
PFS, but not OS, was superior with VEGF mAb compared to EGFR mAbs for pts with RAS MT mCRC. In BRAF MT and triple WT tumors, both PFS and OS did not differ by mAb, but efficacy of EGFR mAbs in triple WT was influenced by sidedness.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Health and Medical Research Council (NHMRC), Australia Fondation A.R.CA.D.
Disclosure
C.S. Karapetis: Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy: MSD; Advisory/Consultancy: Astra Zeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck; Advisory/Consultancy: BMS. A. Grothey: Research grant/Funding (self): Roche/Genentech; Research grant/Funding (self): Array/Pfizer; Research grant/Funding (self): Merck; Research grant/Funding (self): Daichi-Sankyo; Research grant/Funding (self): OBI Pharmaceuticals; Research grant/Funding (self): Boston Biomedicals; Research grant/Funding (self): HalioDx; Research grant/Funding (self): Bayer; Research grant/Funding (self): Astra Zeneca. R.A. Adams: Speaker Bureau/Expert testimony: amgen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serono. A. Venook: Research grant/Funding (self): Genentech/Roche. H.J. Lenz: Advisory/Consultancy: Merck KG; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer. B. Chibaudel: Honoraria (self): sanofi; Honoraria (self): roche; Honoraria (self): bayer; Honoraria (self): beigine; Honoraria (self): lilly; Honoraria (self): servier; Honoraria (self): pfizer. M.E. Buyse: Shareholder/Stockholder/Stock options: IDDI; Full/Part-time employment: IDDI. All other authors have declared no conflicts of interest.