In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3508-3508
Abstract:
3508 Background: The PARADIGM trial (NCT02394795) showed longer median overall survival (OS) with first-line mFOLFOX6 plus panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with RAS wild type (WT) and left-sided metastatic colorectal cancer (mCRC; 37.9 vs 34.3 months, respectively; hazard ratio [HR], 0.82; P=0.031) and similar OS in right-sided pts (HR 1.09; Yoshino T, et al. ASCO 2022 LBA1). Based on current guideline recommendations regarding clinically relevant biomarkers, here we report clinical outcomes in left-sided mCRC pts with microsatellite stable or microsatellite instability low (MSS/MSI-L) and RAS (KRAS/NRAS)/ BRAF (V600E) WT from PARADIGM. Methods: Baseline plasma circulating tumor DNA (ctDNA; 〉 10 ng/mL and 〉 10 nM DNA) from pts enrolled in the biomarker study (NCT02394834) was assessed using a custom panel (PlasmaSELECT-R 91, PGDx). The efficacy (OS, progression-free survival [PFS], response rate [RR] , and curative resection rate [R0]) of PAN plus mFOLFOX6 compared with BEV plus mFOLFOX6 according to RAS, BRAF (V600E), and MSI status and primary tumor location was evaluated. Results: Among 802 pts in the full analysis set, 733 (91%) had evaluable pretreatment samples for ctDNA analysis. Of these pts, 53 (7.2%) and 78 (10.6%) pts had RAS and BRAF ( V600E) mutations, respectively, and 20 (2.7%) pts had MSI high (MSI-H) status. In left-sided mCRC pts with MSS/MSI-L and RAS/ BRAF WT, OS tended to be longer with PAN vs BEV (40.6 [95% CI, 36.3-44.4] vs 34.8 [95% CI, 31.3-41.2] months, respectively; HR, 0.79 [95% CI, 0.64–0.97] ). Although PFS was comparable between PAN (13.6 months [95% CI, 12.6–15.3]) and BEV (12.6 months [95% CI, 11.3–14.1] ; HR, 0.95 [95% CI, 0.77–1.17]), RR and R0 resection rates were higher with PAN (RR: 83.2% [95% CI, 78.0–87.6] ; R0: 18.8% [95% CI: 14.2–24.1]) compared with BEV (RR: 66.4% [95% CI, 60.0–72.3] ; R0: 10.0% [95% CI: 6.5–14.5]). OS was similar or inferior to PAN vs BEV regardless of the primary sidedness in pts with MSI-H or RAS/ BRAF mutations (Table). Conclusions: These results support PAN + mFOLFOX6 as a first-line therapy for left-sided pts with MSS/MSI-L and RAS/ BRAF WT. Clinical trial information: NCT02394795 . [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.16_suppl.3508
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
Permalink