In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 18_suppl ( 2012-06-20), p. LBA4000-LBA4000
Abstract:
LBA4000 Background: EGFR overexpression occurs in 27-50% of esophagogastric adenocarcinomas (OGA), and correlates with poor prognosis. The REAL3 trial evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. Methods: Patients with untreated, metastatic or locally advanced OGA were randomised to EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC+P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST after 4 and 8 cycles. Following IDMC review in October 2011 trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. Results: 553 patients were recruited (EOC 275, mEOC+P 278), with median follow-up 5.0 and 5.2 months respectively. Median OS was 11.3 months with EOC compared to 8.8 months with mEOC+P (HR 1.37: 95% CI 1.07-1.76, p=0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22: 95% CI 0.98-1.52, p=0.068), with RR being 42% compared to 46% (odds ratio 1.16: 95% CI 0.81-1.57, p=0.467). mEOC+P was associated with ↑ G3/4 diarrhoea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but ↓ haem toxicity ( 〉 G3 neutropenia 14% vs 31%). In the mEOC+P arm, OS was significantly improved in patients with G1-3 rash (77%, n=209) on treatment compared to those without (23%, n=63); median OS 10.2 vs 4.3 months (p 〈 0.001), with similar significant improvements seen in RR and PFS. Biomarker analysis in the first 200 patients has not identified other predictive markers associated with P therapy. Multivariate analysis for OS in these patients demonstrated a negatively prognostic role for KRAS mutation (HR 2.1: 95% CI 1.10-4.05, p=0.025) and PIK3CA mutation (HR 3.2: 95% CI 1.01-10.40, p=0.048). Conclusions: Addition of P to EOC chemotherapy was associated with worsening of OS in an unselected advanced OGA population. This may be in part due to lowered doses of O and C in the mEOC+P regimen. Outcomes in patients treated with P varied by grade of skin toxicity.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.18_suppl.lba4000
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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