Abstract P6-11-06: Correlation Comprehensive Geriatric Assessment (CGA) and Inflammation and Nutrition Parameters with Outcome Measures in the Phase III PELICAN Trial for Metastatic Breast Cancer (MBC)
Authors: de Wit M , Honecker F , Wedding U , Waldenmaier D , Dorn J , Warm M , Al-Batran S , Schmidt M , Kreienberg R , Jäger E , Saupe S , Müller L , Burkhard JO , Harbeck N 
Published: April 2011

Abstract
Background: PELICAN is a phase III trial of pegylated liposomal doxorubicin (PLD) vs capecitabine (CAP) as first-line therapy of patients (pts) with MBC. In the elderly pts, a CGA and analyses on biologic parameters on inflammation and nutrition, incorporated in the Prognostic Inflammatory and Nutritional Index (PINI) and Glasgow Prognostic Scale (GPS), were performed and results correlated to time to progression (TTP), overall survival (OS), time to treatment failure (TTF), and toxicity.
Methods: CGA comprised data on activities of daily living (ADL), instrumental activities of daily living (IADL), ECOG and Karnofsky performance score (KPS), comorbidity (CIRS-G), and comedication. According to CGA, pts were classified into groups 1-3, ranging from fit to frail (Balducci 2000). For biologic assessment, blood samples of 86 pts were collected and centrally analysed. PINI was defined as [(CRP (mg/L) x A1GP (mg/L)]/[albumin (g/L) x prealbumin (mg/L)]. For GPS: pts were allocated a score of 2 if CRP &gt;10mg/L and albumin &lt;35g/L; a score of 1 if one parameter abnormal; and score of 0 if no abnormal values.
Results: 210 pts (PLD:105; CAP:105) were randomized, stratified by age & prior anthracycline. Median age was 62y (22-85). Pts received a median of 5 cycles each of PLD and CAP. Median TTP was comparable in both arms (6.7mo PLD vs 7.1mo CAP, p=0.346). There was an insignificant trend for higher GPS and PINI in pts ≥65y. According to CGA, 102 pts were considered fit (group 1, 72%), 21 compromised (group 2, 15%), and 19 frail (group 3, 13%). CGA did not correlate with therapy efficacy. Pts with good KPS of ≥90% (n=46) had a significantly longer TTP vs pts with a worse KPS (n=44) (median KPS 100%: 8.7mo; 90%: 8.6mo; ≥90%: 3.8mo; p=0.0027). Pts with GPS of 0 or 1 had a significantly longer TTP and TTF vs pts with a GPS of 2 (median TTP score 0: 8.3mo, score 1: 9.2mo, score 2: 2.8mo, p=0.0002). Grouping of pts by PINI values (&lt;1; 1-10; &gt;10) showed no correlation with TTP or TTF, and a nonsignificant trend for shorter OS for pts with PINI &gt;10 (p=0.056). Among the analyzed laboratory parameters as single values, CRP showed a significant correlation with TTP (median TTP ≥5mg/L: 10.4mo, &gt; 5 mg/l: 6.2mo, p=0.031) as did serum amyloid A (SAA, median TTP ≥6.8mg/L: 10.4mo, &gt;6.8mg/L: 6.0mo, p=0.026) and serum albumin (median TTP ≥35g/L: 8.3mo, &lt;35g/L: 2.8mo, p=0.009). No significant differences were observed with regard to frequency of AEs or AE-related if stratified according to GPS or PINI. Neither PINI nor GPS correlated with occurrence of overall toxicity grade 3-5; GPS correlated significantly with occurrence of constitutional symptoms (p=0.019).
Conclusions: First-line chemotherapy of MBC pts using PLD or CAP showed similar efficacy with respect to TTP. Incorporation of CGA into a phase III trial is feasible and yields information that would otherwise have been missed. Prospective analyses of parameters of systemic inflammation and nutrition may have prognostic significance regarding TTP, TTF, and potentially OS in pts with breast cancer. Results of CGA, PINI and GPS need to be validated prospectively in treatment algorithms for this population.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-06.