Second-line therapy with Nal-IRI/5-FU/FA after failure of gemcitabine/nab-paclitaxel in advanced pancreatic cancer (PC): Predictive role of 1st-line therapy (PREDICT) and impact of quality of life (QoL).
Authors: Karthaus Meinolf , Schwingel Jerome , Bauer Hans , Ansorge Nikolaus , Barmashenko Gleb , Burkart Christof , Ettrich Thomas Jens , Gerhardt Anke , Hoefling Sabine , Jacobasch Lutz , Koenigsmann Michael , Räth Sebastian , Schulte Markos , Schulte Nadine , Schwarzer Andreas , Siegler Gabriele Margareta , Waldschmidt Dirk , Lutz Manfred P. 
Published: January 2025

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Background:
Metastatic PC has the lowest survival rate of all malignant diseases and is the fourth most common cancer. QoL remains an unresolved issue in PC for patients (pts) after treatment failure of 1
st
-line CTx (TTF1). Nanoliposomal irinotecan (Nal-IRI) with 5-FU/folinic acid (FA) increased survival of PC pts from 4.2 months (mo) to 6.1 mo as compared to 5-FU/FA alone, with a rate of toxicities that may impact QoL. PREDICT is an open label, single arm, multicenter Phase IIIb trial (NCT03468335) and examined 2
nd
-line Nal/IRI/5-FU/FA for PC. Here we report on QoL during 2
nd
-line Nal-IRI after failure of 1
st
-line gemcitabine/nab-Paclitaxel (gem/nab-Pac).
Methods:
In this prospective trial, 151 patients with locally advanced or metastatic PC were treated with biweekly Nal-IRI/5-FU/FA (70 mg/m², 2400 mg/m², 400 mg/m²) after failure of gem/nab-pac (TTF1). Primary end point (EP) was the time to treatment failure of 2
nd
-line therapy (TTF2) and has been reported elsewhere. Secondary EP were QoL and Health related quality of life (HR-QoL) which were evaluated using questionnaires (EORTC QLQC30, QLQ-PAN26, EQ-5D-5L). Evaluation of time to definitive deterioration of QoL (TDD) during 2
nd
-line therapy, defined as the time from screening/baseline until loss of ≥10 points in the EORTC QLQ-C30 was compared to baseline.
Results:
QoL analyses were performed with all QoL evaluable subjects set (QAS). The QAS included 143 pts, of which 48 pts were included in TTF1 high (TTF of 1
st
-line ≥213 d) and 49 pts in the TTF1 low (TTF ≤119 d) cohort, with 79 (54.1%) female and 67 (45.9%) male pts. Mean age was 68.2±8.9 years. Overall, a low global health status / QoL mean score was observed at baseline for TTF1 high and low cohorts (about 48 points), which slightly improved during the study for TTF1 high (3.5±23.7) and slightly worsened for TTF1 low cohort (-0.7±22.5). Substantial improvements were observed for both cohorts in emotional functioning scale at certain study time points (TTF1 high: up to 9.1±25.7, TTF1 low: up to 6.6±17.0). A relatively high mean score was observed for cognitive function scale for both cohorts at baseline (TTF1 high: 70.1±30.2; TTF1 low: 72.5±21.4). Pts in the TTF1 low vs. high cohort showed more pronounced worsening of cognitive function. Median TDD was numerically longer (about one month) for TTF1 high (5,3 mo) compared to TTF1 low cohort (3,9 mo). The probability to maintain QoL after six months was similar between the two cohorts.
Conclusions:
QoL showed similar global and HR-QoL scores with only slight changes during the study. Median TDD was numerically longer for high TTF1 pts, but similar after six months between pts still on 2
nd
line Nal/IRI/5-FU regardless of duration of TTF in 1
st
-line.
Clinical trial information: NCT03468335
.