Résumé
Background: Advances in screening and treatment have led to increase in breast cancer (BC) survival in recent years but prognoses for metastatic BC remain poor with poorer outcomes as health-related quality of life (HRQOL). Treatment as bevacizumab and paclitaxel for metastatic BC, although that can increase time to progression of disease, often carry toxicity and is not curative but rather palliative in intent with the goal to improve or maintain HRQOL. The aim of this work was to assess impact of clinical factors such as disease progression, toxicity on HRQOL. Methods: COMET study is a multicenter prospective single-arm cohort study in France whose main objective was to identify biological factor that could predict the clinical benefit of bevacizumab-paclitaxel combination therapy as first treatment in HER2 negative metastatic BC. HRQOL was assessed at baseline, at every cycle (every for 4 weeks) until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its BC specific module, the EORTC QLQ-BR23. In this ancillary study, we targeted 5 dimensions HRQOL for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). The primary endpoint was time until definitive deterioration (TUDD) in HRQOL scales that defined as time between inclusion and the first decrease HRQOL score ≥ 5 points compared to baseline score, with no further improvement of at least 5 points. Multivariable Cox model with time dependent covariate was performed to assess clinical factors associated with TUDD for each of the 5 target dimensions HRQOL. We performed 3 models for each dimension: model 1 including all covariate with p< 0.10 in univariable; model 2 including model 1 and adjusted on cancer subtype and model 3 included model 1 stratified by cancer subtype. P value < 0.01 were considered statistically significant. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. Median age at inclusion was 58 years (range: 29-83), and 24.4% of patients had triple negative tumor subtype. About 79 % of cancers were invasive ductal carcinoma and 43 % patients had least 3 metastasis sites at baseline. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. In multivariable analyses, Disease Progression was associated with TUDD of GHS (HR [99%CI] =2.4 [1.2-4.9] and TUDD of PF (2.1 [1.1-3.7]). After adjusted on cancer subtype, association persisted with TUDD of GHS (p=0.009). Performance Status was associated with TUDD of PF (1.6 [1.2-2.3]), and TUDD of Pain (1.6 [1.1-2.3]). Performance Status association with TUDD of PF continued after adjustment on cancer subtype (p=0.0003). Prior endocrine therapy was associated with TUDD of pain in patients with tumor with positive hormone receptor (HR+) (2.4 [1.2-4.7]). There was no factor associated with TUDD of EF and TUDD of FA. Conclusion: Results of this study have shown that among the 5 targeted dimensions HRQOL, Physical Functioning was deteriorated in the shortest time. Disease progression, base line performance status and prior endocrine therapy for HR+ subtype, are clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy.
Citation Format: Oumar Billa, Sandrine Dabakuyo, Marion Chevrier, Franck Bonnetain, Isabelle Desmoulins, William Jacot, Olivier Trédan, Marc Debled, Christelle Levy, Anthony Gonçalves, Jean-Marc Ferrero, Florence Dalenc, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Mireille Mousseau, Julien Grenier, Jean-Philippe Jacquin, Fatima-Zohra Toumi, Frédérique Berger, Jérôme Lemonnier, Jean-Yves Pierga. Health related quality of life of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2 negative metastatic breast cancer: impact of clinical factors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-54.