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Background: BEV has been shown to significantly improve the efficacy of both paclitaxel (PAC) and capecitabine (CAP) as first-line therapy for HER2-negative mBC. TURANDOT, a randomized phase III trial comparing BEV-PAC vs BEV-CAP, includes extensive QoL evaluation. Methods: Patients (pts) with HER2-negative mBC who had received no prior chemotherapy for mBC were randomized to receive either BEV-PAC (BEV 10 mg/kg d1 & 15 + PAC 90 mg/m² d1, 8, & 15 q4w) or BEV-CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m² bid d1-14 q3w) until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is overall survival (OS); QoL, assessed using the EORTC QLQ-C30, is a secondary endpoint. Pts were asked to complete QLQ-C30 at baseline, q12w during study therapy, at the end of treatment, and 28 days after discontinuing from the study. Results: On-treatment QoL questionnaires were available from all 561 of the treated pts at baseline, 394 at week 12, 266 at week 24, 186 at week 36, 129 at week 48, and <100 at subsequent assessments. For time points up to week 48, there were more questionnaires available from the BEV-PAC than the BEV-CAP arm; the pattern reversed thereafter. Mean global health score was similar in the two treatment arms with little change from baseline over time. In the BEV-PAC arm, mean baseline score was 58.0, remaining above the baseline score up to week 60; mean changes from baseline ranged from +8.3 at week 96 (n = 4) to -9.2 at week 60; mean changes for time points with data from >50 pts ranged from +1.5 to +2.6. In the BEV-CAP arm, mean baseline score was 56.0; the mean score remained above the baseline mean score until week 96. Mean change from baseline ranged from -3.9 at week 84 to +4.9 at week 96. Mean scores for most individual symptom scales were low (typically <20) at baseline and remained low until week 96, suggesting that symptoms evaluated in QLQ-C30 did not represent a major burden to pts. The highest mean baseline symptom scores in both treatment arms were for fatigue (34.1 with BEVPAC vs 38.8 with BEV-CAP), pain (30.4 vs 34.3, respectively), and insomnia (29.3 vs 32.4, respectively). Mean scores for these symptom scales showed no meaningful increase (representing a deterioration in QoL) over time. Mean scores for the appetite loss and dyspnea scales slightly favored the BEV-CAP arm from week 36 onwards. Scores for financial difficulties fluctuated over time. Physical, role, emotional, cognitive, and social functioning scales showed slight or no change over time and no difference between treatment regimens. Conclusion: Extensive QoL evaluation in the TURANDOT trial revealed no clear difference in global health score and little or no difference in functioning and symptom scales between the treatment regimens. Importantly, BEV-containing therapy was not associated with a deterioration in global health score in either arm. This has important implications when considering the potential benefit of a treatment, particularly in the first-line mBC setting, where clinically meaningful endpoints continue to be debated. [ABSTRACT FROM AUTHOR]

Background. We earlier reported patient-related factors influencing the delay in first medical advice for signs of BC in selected countries (J Clin Oncol 2012;30[15S]:578s). The present analysis, which includes additional countries, addresses the factors influencing time from first symptoms of BC to initiation of treatment (Total Delay Time; TDT). Methods. A total of 6,588 female BC patients from 11 countries were surveyed using a uniform questionnaire translated into local languages. TDT was determined using 8 individual scales, including one pertaining to patient delay and 7 related to subsequent steps in a typical diagnostic process. Regression models were constructed using 18 variables concerning diverse contextual and personal patient characteristics. Due to expected differences in the relevant sets of predictors, time between first symptoms and first medical visit (Patient Delay Time; PDT) and time between first medical visit and start of therapy (System Delay Time; SDT) were modeled separately, with multilevel regression. Results. Mean TDT varied in individual countries from 11.5 to 29.4 weeks (grand mean of 14.3 weeks; see table), with 43% of cases with a delay of >12 weeks. Multilevel regression equation indicated that factors significantly correlated with longer PDT were distrust in the medical system and ignoring disease. Patients with fear of the disease, stronger self-examination habits, at least secondary education, being employed, reporting more support from friends and family, and living in cities of >100,000 inhabitants had shorter PDT. Predictors of shorter SDT included being diagnosed by an oncologist vs. other physician, having at least secondary education, being older than 60 years, having a history of cancer in female relatives and having breast lump vs. other BC symptoms. Indicators of longer SDT were PDT >4 weeks, more than one BC symptom detected by patient, distrust in the medical system, disregard of BC signs, less support from friends and family, and having first medical examination in a public vs. private medical center. Individual countries differed significantly with regard to intercept of the multilevel models and slopes of regression coefficients for selected psychological and behavioral attributes. Conclusions. An extensive set of variables potentially impacting delay times, mainly related to psychological and behavioral patient attributes, was examined. Several of them strongly determined both PDT and SDT, but their strength differed between individual countries. Both models (for PDT and SDT), although statistically significant, accounted for approximately 20% of variance in time; therefore other variables, e.g. related to the differences in national healthcare systems (not addressed in this study) might have a stronger impact on delays in the initiation of BC therapy and warrant further analyses. [ABSTRACT FROM AUTHOR]

Purpose: Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy., Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model., Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms., Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted., (©2023 The Authors; Published by the American Association for Cancer Research.)