Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial.
Publication: Journal of Clinical Oncology
Abstract
LBA1
Background: PARADIGM is the first prospective trial to test the superiority of PAN vs. BEV in combination with standard doublet first-line chemotherapy for patients (pts) with RAS WT mCRC and left-sided primary tumors. Methods: This open-label, multicenter trial in Japan (NCT02394795) randomly selected pts with chemotherapy-naive RAS WT mCRC to PAN + mFOLFOX6 or BEV + mFOLFOX6. Overall survival (OS) as primary endpoint was hierarchically tested in patients with left-sided tumors, followed by those in the full-analysis set (FAS) population. Key secondary endpoints included progression-free survival (PFS), response rate (RR), and curative resection (R0) rate. Results: From May 2015 to June 2017, 823 pts were randomized; 12 did not receive protocol treatment and 9 were excluded due to major deviation of inclusion criteria. A total of 400 pts received PAN and 402 pts received BEV as FAS; 312 and 292 pts had left-sided primary tumors, respectively. OS was analyzed after 448 OS events in left-sided pts with a median follow-up of 61 months. PAN significantly improved OS vs. BEV in both populations: left-sided (HR, 0.82; 95.798% CI, 0.68-0.99, p = .031, which crossed the boundary of significance [0.042]), and FAS (HR, 0.84; 95% CI, 0.72-0.98; p = .030, with < 0.05 as the boundary). Although PFS was comparable between treatment groups, RR and R0 resection rates were higher with PAN compared with BEV (Table). HR for OS in the right-sided population was 1.09. No new safety signal was observed. Conclusions: PAN significantly improved OS vs. BEV in combination with mFOLFOX6 in pts with RAS WT and left-sided mCRC, establishing a standard first-line combination regimen for this population. Clinical trial information: NCT02394795.PARADIGM efficacy outcomes.
PAN + mFOLFOX6 | BEV + mFOLFOX6 | HR (CI)a | Pp value | |
---|---|---|---|---|
Left-sided tumor population | n=312 | n=292 | ||
Median OS, mo | 37.9 (34.1-42.6) | 34.3 (30.9-40.3) | 0.82 (0.68-0.99) | 0.031 |
Median PFS, mo | 13.7 (12.7-15.3) | 13.2 (11.4-14.5) | 0.98 (0.82-1.17) | |
RR, % | 80.2 (75.3-84.5) | 68.6 (62.9-74.0) | ||
R0 resection, % | 18.3 (14.1-23.0) | 11.6 (8.2-15.9) | ||
FAS population | n=400 | n=402 | ||
Median OS, mo | 36.2 (32.0-39.0) | 31.3 (29.3-34.1) | 0.84 (0.72-0.98) | 0.030 |
Median PFS, mo | 12.9 (11.3-13.6) | 12.0 (11.3-13.5) | 1.01 (0.87-1.18) | |
RR, % | 74.9 (70.3-79.1) | 67.3 (62.4-71.9) | ||
R0 resection, % | 16.5 (13.0-20.5) | 10.9 (8.1-14.4) |
aConfidence intervals: 95.798% CI for OS in left-sided pts; 95% CI for other brackets.
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© 2022 by American Society of Clinical Oncology.
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Published online: June 08, 2022
Published in print: June 10, 2022
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Japan Medical Affairs, Japan Oncology Business Unit, Takeda Pharmaceutical Company Ltd., Tokyo, Japan.
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Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial.. JCO 40, LBA1-LBA1(2022).
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Journal of Clinical Oncology 2022 40:17_suppl, LBA1-LBA1
Journal of Clinical Oncology 2022 40:17_suppl, LBA1-LBA1
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