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| © 2009 Elsevier Ltd. All rights reserved. |
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Joint ECCO 15 - 34TH ESMO
Multidisciplinary Congress
BERLIN, 20 - 24 SEPTEMBER 2009
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Abstract P-6083:
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| Final results from PRECEPT: efficacy and safety of second-line treatment with panitumumab and FOLFIRI in patients with metastatic colorectal cancer (mCRC) |
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Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 347
A. Cohn1, D.A. Smith2, M.A. Neubauer3, D. Richards4, D.L. Watkins5, K. Zhang6, M. Yassine7
1Rocky Mountain Cancer Center, Research, Denver CO, USA
2Northwest Cancer Specialists PC, Hematology/Oncology, Vancouver WA, USA
3Kansas City Cancer Center, Medical Oncology, Overland Park KS, USA
4Texas Oncology, Medical Oncology, Tyler TX, USA
5USO-Allison Cancer Center, Medical Oncology, Midland TX, USA
6Amgen Inc., Biostatistics, South San Francisco CA, USA
7Amgen Inc., Scientific Affairs, Mississauga ONT, Canada
Background: Panitumumab (pmab) is a fully human antibody against the epidermal growth factor receptor (EGFR), a therapeutic target in patients (pts) with mCRC. Response to anti-EGFR therapies can be predicted by mutation status of KRAS in tumors. This prospective analysis evaluated the effect of tumor KRAS status on efficacy of second-line pmab+FOLFIRI.
Methods: Pts with unresectable, measurable mCRC (ECOG status 0/1) were enrolled in this phase 2, open-label, single-arm study after failure of first-line treatment with oxaliplatin-based chemotherapy+bevacizumab (ClinicalTrials.gov ID: NCT00411450; sponsor: Amgen). Pts received pmab 6 mg/kg + FOLFIRI Q2W until disease progression or intolerability. Tumor assessments were performed at weeks 8, 16, 24, 32, and Q12W thereafter. KRAS status was determined by real-time PCR on DNA extracted from fixed tumor sections. Efficacy endpoints included objective response (per investigator), progression-free survival (PFS), and overall survival (OS). Safety endpoints included incidence of adverse events (AEs). Endpoints were evaluated by tumor KRAS status.
Results: 109 pts enrolled in the study and received ≥1 dose of pmab; 59% had tumors with wild-type (WT) KRAS, 41% had tumors with mutated (MT) KRAS. Efficacy outcomes (excluding 2 pts missing information at baseline) are shown (Table). Hazard ratios (95% CL) by KRAS status were 0.8 (0.5, 1.1) for PFS and 0.6 (0.4, 0.9) for OS. Pmab-related AEs were reported in 93% of pts; 94 pts (82%) had grade ≥3 AEs (related and unrelated). The most common AEs (WT/MT KRAS) were diarrhea (81%/62%), nausea (53%/58%), fatigue (55%/47%), rash (50%/56%), and acneiform dermatitis (41%/36%). The most common serious AEs were dehydration (10% of all pts), pyrexia (5%), and deep vein thrombosis (3%).
Conclusions: Numerical differences in PFS and OS in favor of pts with WT KRAS were observed. Pmab had a safety profile consistent with other pmab+FOLFIRI trials in pts of the same study population.
| Best Objective Responsea, n (%) | WT KRAS (N = 64) | MT KRAS (N = 43) |
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| Complete responseb | 2 (3) | 1 (2) |
| Partial responseb | 13 (20) | 6 (14) |
| Stable disease | 26 (41) | 18 (42) |
| Disease progression | 13 (20) | 11 (26) |
| Unable to evaluate/not done | 10 (16) | 7 (17) |
| Objective response rate, n responders | 15 | 7 |
| Response rate, % (95% CL) | 23 (13, 34) | 16 (5, 27) |
| PFS, n events | 54 | 43 |
| Median weeks (95% CL) | 26 (19, 33) | 19 (12, 25) |
| OS, n deaths | 34 | 36 |
| Median weeks (95% CL) | 50 (39, 76) | 31 (23, 47) |
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| aPrimary analysis set (N = 107); bConfirmed at next assessment. |
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