Abstract GS3-02: Patient-reported outcomes (PROs) from the Ph 3 IMpassion031 trial of neoadjuvant (NA) atezolizumab + chemo in early triple-negative breast cancer (eTNBC)
Authors: Mittendorf Elizabeth A. , Harbeck Nadia , Zhang Hong , Saji Shigehira , Jung Kyung Hae , Patel Sheetal , Patel Shilpen , Duc Anh Nguyen , Liste-Hermoso Mario , Chui Stephen Y. , Barrios Carlos H. 
Published: February 2021

Abstract
Background: In IMpassion031 (NCT03197935), patients (pts) (N = 333) with invasive stage II or III eTNBC who received NA treatment (tx) with atezolizumab (A) + nab-paclitaxel (nP) followed by doxorubicin + cyclophosphamide (AC; A-chemo) had significantly improved pathologic complete response (pCR, primary endpoint) regardless of PD-L1 status vs placebo (P) with nP and AC (P-chemo). Balancing efficacy and toxicity is key in this potentially curable eTNBC setting. PROs were collected to comprehensively assess tx burden from the pts’ perspective, inform clinical benefit and decision-making and address the lack of pt-reported data in this setting. Methods: Pts received double-blind A 840 mg or P every 2 weeks (q2w) with nP 125 mg/m2 once weekly for 12 wk followed by A 840 mg or P q2w with AC q2w for 4 doses. After surgery and pathological evaluation, pts in the A-chemo arm received open-label A 1200 mg every 3 weeks for 11 doses. The P-chemo arm was observed. To capture pts’ experience of tx-related symptoms, associated bother, and impact on day-to-day functioning and health-related quality of life (HRQoL), pts completed the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and single-item GP5 from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline (BL) and day (D)1 of each cycle (C) of NA and adjuvant (adj) tx, at end of tx and in follow-up every 3 mo (year 1), every 6 mo (years 2-3), then annually. Mean and mean change from BL scores (≥ 10-point change considered clinically meaningful) by C and between tx arms in the QLQ-C30 function (role and physical) and global health status/QoL scales were predefined secondary endpoints. Mean and mean change from BL scores in tx-related symptoms, as well as an assessment of tx side-effect bother, were exploratory endpoints. Results: QLQ-C30 completion rates (ITT) in both arms were 100% at BL and &gt; 90% in the NA phase and &gt; 89% in the adj phase through C16. GP5 completion rates in both arms were &gt; 98% at BL (C2D1) and &gt; 88% in the NA and adj phases. BL mean [95% CI] values were high for physical function (A-chemo, 91 [89-93]; P-chemo, 90 [88-92]), role function (A-chemo, 89 [86-93]; P-chemo, 89 [86-92]), and HRQoL (A-chemo, 79 [76-82]; P-chemo, 76 [73-79]). Physical and role function, and HRQoL mean values were similar between arms across on-tx assessments to C16 and through follow up. Mean change from BL values for physical and role function, and HRQoL were similar between arms and of the same magnitude. In both arms mean physical function had a clinically meaningful decline during the NA period from C3 to C5, rebounding in the adj period, and stabilizing starting C7. In both arms mean role function had a clinically meaningful decline in the NA period from C2 (A-chemo) or C3 (P-chemo) to C5, rebounding in the adj period, and stabilizing at C9 in the P-chemo arm only. In both arms mean HRQoL had a clinically meaningful decline in the NA period from C3 to C5, rebounding in the adj period and stabilizing from C6. Tx symptoms of fatigue, diarrhea, nausea, and vomiting in the NA period worsened through C5 in both arms with trends in mean and mean change from BL values similar to the functional and HRQoL data. In the adj period, mean symptom scores in both arms through C16 were similar to BL except for fatigue. 65% (A-chemo) and 66% (P-chemo) of pts reported their level of bother with tx side effects to be “somewhat” or “quite a bit” by C5. During the adj period, no added side-effect bother was experienced by pts receiving A compared with the P-chemo arm under observation, with a similar % of pts in each arm reporting being bothered “somewhat,” “quite a bit,” or “very much” by C16. Conclusions: Adding A to nP-AC improved pCR without added tx burden to pts. These results address the paucity of PRO data informing clinical benefit and decision-making in this potentially curable setting.
Citation Format: Elizabeth A. Mittendorf, Nadia Harbeck, Hong Zhang, Shigehira Saji, Kyung Hae Jung, Sheetal Patel, Shilpen Patel, Anh Nguyen Duc, Mario Liste-Hermoso, Stephen Y. Chui, Carlos H. Barrios. Patient-reported outcomes (PROs) from the Ph 3 IMpassion031 trial of neoadjuvant (NA) atezolizumab + chemo in early triple-negative breast cancer (eTNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-02.