Abstract P5-16-01: Assessment of health-related quality of life by clinical response from the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC)
Authors: Loibl Sibylle , Tolaney Sara M. , Punie Kevin , Oliveira Mafalda , Rugo Hope S. , Bardia Aditya , Hurvitz Sara A. , Brufsky Adam , Kalinsky Kevin M , Cortes Javier , O’Shaughnessy Joyce , Carey Lisa A. , Gianni Luca , Diéras Véronique , Shi Ling , Gharaibeh Mahdi , Preger Luciana , Moore Lee , Phan See , Piccart Martine 
Published: March 2022

Abstract
Background: In ASCENT, patients with mTNBC refractory to or relapsing after ≥2 prior chemotherapies (at least one in the metastatic setting) were randomized 1:1 to receive sacituzumab govitecan (SG) or single-agent treatment of physician’s choice (TPC) (capecitabine, eribulin, vinorelbine, or gemcitabine). Primary endpoint was progression free survival. Secondary endpoints included overall survival, objective response rate, clinical benefit rate, and safety. Here we examined whether health-related quality of life (HRQoL) differed by clinical response. Methods: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30) version 3 was used to assess HRQoL at baseline and on day 1 of each treatment cycle. This analysis included intention-to-treat patients who had a completed at least one of the 15 domains/scales at baseline and at least one evaluable assessment at post-baseline visits based on EORTC QLQ-C30. Patients were classified as responders (partial or complete disease response) or non-responders (stable or progressive disease or not evaluable) based on best overall response (RECIST). A mixed-effect model for repeated measures (MMRM) was used to estimate leastsquare (LS) mean EORTC QLQC30 score changes from baseline using all HRQoL data assessed during Cycle 2 Day 1 (C2D1) to C6D1 (where n was ≥25 in both treatment arms) for responders and nonresponders within each treatment group. Results: Mean QLQ-C30 subscale scores at baseline were similar between treatment arms. The analysis included 236 patients in the SG arm of the full trial population, of whom 82 (35%) were clinical responders; and 183 in the TPC arm, of whom 11 (6%) were clinical responders. Due to the small number of TPC responders, inferential statistical testing to compare between-group difference was not performed.Irrespective of their clinical response status, patients treated with SG showed more favorable LS mean changes than patients who received TPC in all EORTC QLQ-C30 domains, except for nausea/vomiting and diarrhea (Table). Overall, LS mean changes in EORTC QLQ-C30 scores in SG nonresponders were less favorable than those in SG responders, but more favorable than those in TPC responders and TPC nonresponders for most EORTC QLQ-C30 domains. Conclusions: The analysis demonstrates that regardless of response status, SG responders and non-responders showed a better trend in HRQoL changes than TPC. Patients who achieved a tumor response to SG may benefit most in HRQoL. Although patients treated with SG reported higher rates of diarrhea, this did not generate a negative impact on their overall quality of life or functioning.
Table: Mixed effects model least-square mean EORTC QLQ-C30 score changes from baselineLeast-square mean change from baseline (95% confidence interval)SG responders(N=82)SG nonresponders(N=154)TPC responders(N=11)TPC non-responders(N=172)Global health status/QoL2.46 (-1.52, 6.43)-0.57 (-3.68, 2.54)-1.64 (-10.22, 6.95)-2.29 (-5.63, 1.05)FunctioningPhysical2.93 (-0.92, 6.79)0.22 (-2.71, 3.15)-3.47 (-11.93, 4.99)-3.75 (-6.87, -0.63)Role-0.35 (-5.74, 5.04)-3.23 (-7.45, 0.99)-8.40 (-19.93, 3.13)-7.33 (-11.88, -2.78)Emotional6.20 (2.23, 10.18)1.97 (-1.12, 5.06)4.87 (-3.70, 13.44)0.08 (-3.24, 3.40)Cognitive0.90 (-2.99, 4.79)-2.25 (-5.26, 0.76)-4.46 (-12.87, 3.95)-1.26 (-4.49, 1.98)Social2.06 (-3.50, 7.61)-3.35 (-7.65, 0.95)-5.79 (-18.29, 6.72)-4.36 (-8.99, 0.27)SymptomsFatigue0.90 (-3.49, 5.28)2.84 (-0.60, 6.29)4.15 (-5.34, 13.65)6.65 (2.93, 10.38)Nausea/vomiting4.68 (1.42, 7.95)4.03 (1.42, 6.64)1.38 (-5.53, 8.29)2.62 (-0.21, 5.45)Pain-11.40 (-16.43, -6.36)-8.57 (-12.48, -4.66)-11.99 (-22.85, -1.13)-0.24 (-4.47, 3.99)Dyspnea-7.88 (-13.09, -2.67)-1.90 (-5.93, 2.13)1.97 (-9.33, 13.27)3.86 (-0.47, 8.18)Insomnia-6.12 (-11.99, -0.26)-3.51 (-8.04, 1.02)4.83 (-7.85, 17.51)-0.98 (-5.86, 3.90)Appetite loss0.22 (-5.25, 5.70)5.45 (1.15, 9.75)8.67 (-3.05, 20.40)4.60 (-0.05, 9.26)Constipation0.93 (-4.57, 6.43)2.20 (-2.09, 6.49)3.87 (-7.96, 15.70)3.52 (-1.12, 8.16)Diarrhea16.03 (10.32, 21.74)13.65 (9.19, 18.11)2.46 (-9.88, 14.80)-1.53 (-6.34, 3.29)Financial difficulties-3.57 (-8.54, 1.39)-2.44 (-6.21, 1.34)-4.41 (-15.27, 6.46)0.61 (-3.42, 4.64)A higher score for a functional domain represents a higher or healthier level of functioning; a higher score for the global health status/QoL represents a higher overall HRQoL; but a higher score for a symptom domain represents a higher level of symptomatology or problems
Citation Format: Sibylle Loibl, Sara M. Tolaney, Kevin Punie, Mafalda Oliveira, Hope S. Rugo, Aditya Bardia, Sara A. Hurvitz, Adam Brufsky, Kevin M Kalinsky, Javier Cortes, Joyce O’Shaughnessy, Lisa A. Carey, Luca Gianni, Véronique Diéras, Ling Shi, Mahdi Gharaibeh, Luciana Preger, Lee Moore, See Phan, Martine Piccart. Assessment of health-related quality of life by clinical response from the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-01.