Abstract 269P
Background
In EMBRACA, TALA vs PCT demonstrated significant improvement in progression-free survival, a manageable adverse event (AE) profile, and quality of life (QoL) improvement. AEs were managed with supportive care and dose modifications. This post hoc analysis evaluated PROs in TALA pts without/with dose reductions vs PCT.
Methods
431 pts were randomized 2:1 to TALA (1 mg/d; n=287) or PCT (n=144); 52% of pts in the TALA arm had dose reductions (0.75 mg, 0.5 mg, or 0.25 mg). PROs were assessed at baseline, Day 1 of each 3 wk cycle, and end of treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and BC module (BR23). Higher scores indicate better functioning or global health status (GHS)/QoL, or worse symptoms. PRO analyses included overall (longitudinal mixed effects model) mean change from baseline and time to definitive (TTD) clinically meaningful deterioration for TALA pts without/with dose reductions vs PCT. TTD was compared using a stratified log-rank test and Cox proportional hazards model.
Results
Between arm overall change from baseline significantly favored TALA without/with dose reduction vs PCT in GHS/QoL, functional (physical, role, emotional, social), and symptom (fatigue, pain, insomnia, appetite loss) scales (Table). A delay in TTD was observed in GHS/QoL with TALA vs PCT in pts without (not reached vs 6.3 mo; hazard ratio [HR]=0.42 [95% CI: 0.26, 0.66]; P=0.0001) and with (16.9 vs 6.3 mo; HR=0.35 [0.22, 0.54]; P<0.001) dose reductions. Additional PRO results from the BR23 module will be presented. Table: 269P
Model estimated between arm overall change from baseline (EORTC QLQ-C30)
| TALA without Dose reduction vs PCT | P-Value | TALA with Dose reduction vs PCT | P-Value | |
| GHS/QoL, & Function | ||||
| GHS/QoL | 9.4 | <0.001 | 7.5 | <0.001 |
| Physical | 10.5 | <0.001 | 9.1 | <0.001 |
| Role | 12.5 | <0.001 | 11.7 | <0.001 |
| Emotional | 8.3 | 0.001 | 5.9 | 0.028 |
| Cognitive | 2.8 | 0.247 | 6.9 | 0.006 |
| Social | 8.3 | 0.004 | 9.6 | 0.004 |
| Symptom | ||||
| Fatigue | -13.1 | <0.001 | -11.0 | <0.001 |
| Pain | -11.0 | <0.001 | -13.6 | <0.001 |
| Nausea/vomiting | -4.5 | 0.099 | -3.2 | 0.121 |
| Dyspnea | -6.4 | 0.015 | -2.5 | 0.398 |
| Insomnia | -8.4 | 0.006 | -7.6 | 0.005 |
| Appetite loss | -13.4 | <0.001 | -10.5 | <0.001 |
| Diarrhea | -2.9 | 0.037 | -2.1 | 0.192 |
| Constipation | -5.7 | 0.034 | -3.9 | 0.211 |
Conclusions
In these subgroup analyses evaluating PROs in pts without/with TALA dose reductions vs PCT, improvement in GHS/QoL, and several functional and symptom scales were observed regardless of dose reductions.
Clinical trial identification
NCT01945775.
Editorial acknowledgement
Editorial support was provided by Jill Shults, PhD, of ICON plc (North Wales, PA, USA), and was funded by Pfizer Inc.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer Inc; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Odonate; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Sermonix; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Polyphor; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Honoraria: PUMA; Financial Interests, Personal, Other, Honoraria: Samsung; Financial Interests, Personal, Other, Honoraria: Mylan; Financial Interests, Institutional, Research Grant: Immunomedics. A. Niyazov, H. Bhattacharyya, B. Arondekar: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. All other authors have declared no conflicts of interest.