In phase IIIb PROMID, oct l-a (30mg intramuscular/monthly) significantly extended time to tumor progression (HR = 0.34; 95% CI: 0.20, 0.59; p = 0.000072) compared with PBO in treatment-naïve pts with well-differentiated mmNETs. We report post-hoc analyses for HRQoL.
HRQoL was measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30), a 30-item self-report questionnaire with 5 functional, 1 global, and 9 symptom scales. Assessments were completed at baseline and every 12 wks until tumor progression. Time to definitive deterioration (TDD) was analyzed with the Kaplan-Meier method (using ≥10 points minimal important difference, range 0-100); distributions were compared using a stratified log-rank test adjusting for tumor functionality. Linear mixed models were fit to assess change from baseline in QLQ-C30 scores by treatment arm over time.
Of 85 pts enrolled between 2001 and 2008, 82 (96%) completed the QLQ-C30 at baseline (oct l-a: 40, PBO: 42). There were few events of definitive deterioration for most scales. Median TDD was not reached in 11/15 scales for oct l-a and 5/15 scales for PBO. Significantly longer TDD was reported for oct l-a vs. PBO for fatigue (median 6.8 months vs 18.5; p = 0.0006), pain (not reached (NR) vs 18.2; p = 0.0435), and insomnia (NR vs 16.4; p = 0.0046). Change from baseline to wk 24 fatigue scores were stable for oct l-a (least squares [LS] mean 0.78 (95% CI -6.3: 7.8) but worsened for PBO (LS mean 9.1; 95% CI 1.9: 16.4); with mean difference -8.4 (95% CI -18.5: 1.8). For diarrhea there were improvements for oct l-a (LS mean -8.0; 95% CI -19.6: 3.5) and worsening for PBO (LS mean 11.2; 95% CI -0.7: 23.1); with mean difference -19.3 (95% CI: -36.1; -2.5).
These post-hoc analyses showed significantly longer TDD for oct l-a vs. PBO in pts with mmNET for symptoms relevant in NET: fatigue, pain, and insomnia; alongside improved tumor control. Change from baseline showed that HRQoL was maintained in oct l-a pts whereas significant deterioration for some symptoms was observed in PBO pts, further supporting HRQoL benefits of oct l-a treatment.
Clinical trial identification
SMS995ADE05 / NCT00171873.
Legal entity responsible for the study
Novartis Pharmaceuticals Incorporated.
Novartis Pharmaceutical Corporation.
A. Rinke: Advisory boards: Novartis, Ipsen. M.P. Neary: Employee: Novartis Pharmaceuticals Corporation. J. Eriksson, M. Hunger: Employee: ICON plc. T. Doan, D. Karli: Employee: Novartis Ireland Ltd. All other authors have declared no conflicts of interest.