Natasha Woodward

This study aimed to investigate nutritional status, body composition, dietary protein intake, handgrip strength, 6 min or 4 m walk tests, self-reported physical activity, physical function, and quality of life (QoL-EORTC-QLQc30) at commencement of chemotherapy; to detect changes over time (from commencement of chemotherapy, and after 3, 6, 12, 26 and 52 weeks) in women with metastatic breast cancer (MBC); and to investigate the relationship between nutritional variables. ‘Sarcopenia’ was defined as low muscle mass and strength, ‘myosteatosis’ as muscle fat-infiltration (CT scan). Continuous variables were analysed using paired t-tests between baseline and follow-ups. Fifteen women (54y, 95% CI [46.3;61.2]) were recruited. At baseline, malnutrition was present in 3 (20%) participants, sarcopenia in 3 (20%) and myosteatosis in 7 (54%). Thirteen (87%) participants had low protein intake; low handgrip strength was observed in 0, and low walk test distance and physical activity in four (27%) participants. Physical function and QoL were low in 10 (67%) and 9 (60%), respectively. QoL between baseline and 52 weeks decreased by 11.7 (95% CI [2.4;20.9], p = 0.025). Other variables did not significantly change over time. In this small study sample, myosteatosis, low dietary protein intake, low exercise levels and impaired quality of life and physical function are common.

Purpose: Review of utilization and efficacy of eribulin in Australian metastatic breast cancer (MBC) patients.Methods: Retrospective review of consecutive MBC patients treated with eribulin in tertiary Australian BC centers. Key inclusion criteria included eribulin administration in nonclinical trial setting from October 2014 onwards, known duration of MBC systemic treatments administered and known follow‐up date after eribulin. Cox regression model was used to assess survival.Results: Study population comprised 266 patients from eight centers treated between October 2014 and May 2018. Median age at time of MBC diagnosis was 54 years with 18% of patients having de novo MBC. Seventy‐six percent had hormone receptor positive (HRp) disease, 19% triple negative (TN) and 5% HER2‐positive. CNS involvement was present in 36% of patients. Eribulin was most frequently given as third‐line chemotherapy (36%), with no prior anthracycline exposure in 14% of total population. Eribulin was given more frequently as ≤third‐line chemotherapy than > third‐line in patients with TN disease, ≥ two metastatic sites or CNS disease. Median overall survival (OS) from eribulin administration was 9.2 (95% CI [8.0, 10.3]) months.Conclusion: Similar efficacy was demonstrated for eribulin when given in the first‐line to beyond the fifth line of chemotherapy in all subtypes of MBC.

ABBV-176 is an antibody-drug conjugate composed of the humanized antibody h16f (PR-1594804) conjugated to a highly potent, cytotoxic cross-linking pyrrolobenzodiazepine dimer (PBD; SGD-1882) targeting the prolactin receptor (PRLR), which is overexpressed in several solid tumor types. This phase 1, dose-escalation study (NCT03145909) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-176 in patients with advanced solid tumors likely to exhibit elevated levels of PRLR. Patients received ABBV-176 once every 3 weeks. Dose escalation was by an exposure-adjusted, continual reassessment method. Dose-limiting toxicities (DLTs) were assessed from the first day of dosing until the next dose of ABBV-176 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Nineteen patients received ABBV-176 at doses from 2.7–109.35 μg/kg. Patients enrolled had colorectal cancer (n = 11), breast cancer (n = 6), or adrenocortical carcinoma (n = 2). DLTs occurred in 4 patients and included thrombocytopenia (n = 2; both at 99.9-μg/kg dose level), neutropenia (n = 2; 78.3-μg/kg and 99.9-μg/kg dose levels), and pancytopenia (n = 1; 109.35-μg/kg dose level). The most common treatment-emergent adverse events related to ABBV-176 were thrombocytopenia, neutropenia, increased aspartate aminotransferase, nausea, fatigue, and pleural effusions. Effusions and edema were common, and timing of onset suggested possible cumulative ABBV-176 toxicity. Tumor expression of PRLR varied among patients enrolled and analyzed. No patient had an objective response. MTD was not formally determined, as identification of a tolerable dose was confounded by late-onset toxicities. ABBV-176 was associated with significant toxicity in this phase 1, dose-escalation study. Although cytopenias were often dose limiting, effusions and edema were also common and had late onset that suggested cumulative toxicity. No responses were observed, although data were available from a small number of patients with variable tumor PRLR expression. This study was terminated after the dosing of 19 patients.

Background Survival for stage I to III, hormone receptor‐positive, breast cancer has substantially improved over time due to advances in screening, surgery and adjuvant therapy. However many adjuvant therapies have significant treatment‐related toxicities, which worsen quality of life for breast cancer survivors. Postmenopausal women with hormone receptor‐positive breast cancer are now prescribed aromatase inhibitors (AI) as standard, with longer durations of therapy, up to 10 years, being considered for certain women. AI treatment is associated with a high incidence of AI‐induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS reduces compliance with AI therapy in up to one half of women undergoing adjuvant AI therapy, potentially compromising breast cancer outcomes. Exercise has been investigated for the prevention and treatment of AIMSS but the effect of this intervention remains unclear. Objectives To assess the effects of exercise therapies on the prevention or management of aromatase inhibitor‐induced musculoskeletal symptoms (AIMSS) in women with stage I to III hormone receptor‐positive breast cancer. Search methods We searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases up to 13 December 2018. We also searched two conference proceedings portals and two clinical trials registries for ongoing studies or unpublished trials, or both, in August 2019. We also reviewed reference lists of the included studies. Selection criteria We included randomised controlled trials that compared exercise versus a comparator arm. We did not impose any restriction on the comparator arm, which could include an alternative type of exercise, no exercise or a waiting list control. Both published and non‐peer‐reviewed studies were eligible. Data collection and analysis Two review authors independently extracted data, assessed risk of bias and certainty of the evidence using the GRADE approach. The outcomes investigated were pain, joint stiffness, grip strength, health‐related quality of life, cancer‐specific quality of life, adherence to AI therapy, adverse events, incidence of AIMSS, breast cancer‐specific survival and overall survival. For continuous outcomes that were assessed with the same instrument, we used the mean difference (MD); for those outcomes that used different instruments, we used the standardised mean difference (SMD) for the analysis. For dichotomous outcomes, we reported outcomes as an odds ratio (OR). Main results We included seven studies with 400 randomised participants; one study assessed exercise for preventing AIMSS and six studies assessed treating AIMSS. For preventing AIMSS, the single study reported no difference in pain scores, grip strength or compliance to taking AI medication between groups. Data values were not provided in the study and no other outcomes were reported. For managing AIMSS, we found that the evidence for the effect of exercise therapies on overall change in worst pain scores was very uncertain (SMD −0.23, 95% confidence interval (CI) −0.78 to 0.32; 4 studies, 284 women; very low‐certainty evidence). The evidence suggested that exercise therapies result in little to no difference in overall change in stiffness scores (Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) stiffness score MD −0.76, 95% CI −1.67 to 0.15 and Visual Analogues Scale (VAS) stiffness score MD −0.42, 95% CI −2.10 to 1.26; 1 study, 53 women; low‐certainty evidence). The evidence was very uncertain for the outcomes of overall change in grip strength (MD 0.30, 95% CI −0.55 to 1.15; 1 study, 83 women; very low‐certainty evidence); overall change in health‐related quality of life (subscales of SF‐36 tool ranged from least benefit of MD 1.88, 95% CI −2.69 to 6.45 to most benefit of MD 9.70, 95% CI 1.67 to 17.73; 2 studies, 123 women, very low‐certainty evidence); overall change in cancer‐specific quality of life (MD 4.58, 95% CI −0.61 to 9.78; 2 studies, 136 women; very low‐certainty evidence); and adherence to aromatase inhibitors (OR 2.43, 95% CI 0.41 to 14.63; 2 studies, 224 women; very low‐certainty evidence). There were no adverse events identified across four studies in either arm (0 events reported; 4 studies; 331 participants; low‐certainty evidence). There were no data reported on incidence of AIMSS, breast cancer‐specific survival or overall survival. Authors' conclusions Given the wide‐ranging benefits of exercise for people affected by cancer, it was surprising that this review provided no clear evidence of benefit for exercise therapies in women with early breast cancer with AIMSS. This review only yielded seven eligible studies with 400 participants, which is likely to have underpowered the findings. The meta‐analysis was challenging due to the considerable heterogeneity amongst the trials, with a wide range of exercise regimens and follow‐up periods. Despite these inconclusive findings, exercise needs to be part of routine care for women with breast cancer due to its wide‐ranging benefits. Future research in this area would be enhanced with further understanding of the mechanism of AIMSS, a single clear definition of the condition, and phase III randomised controlled trials that are adequately powered to test targeted exercise interventions on the key clinical outcomes in this condition.

Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) with physician’s choice of chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) in locally advanced or metastatic breast cancer with a germline BRCA1/2 (gBRCA1/2) mutation. Prespecified patient subgroups were analyzed for progression-free survival, objective response, clinical benefit, duration of response, and safety. PROs were evaluated in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) or triple-negative breast cancer (TNBC) subgroups. Of 431 patients, 287 were randomly assigned to talazoparib and 144 to PCT. Prespecified subgroup analyses showed prolonged progression-free survival with talazoparib (HR+/HER2−: hazard ratio = 0.47, 95% confidence interval = 0.32 to 0.71; TNBC: hazard ratio = 0.60, 95% confidence interval = 0.41 to 0.87) and greater objective response rate (odds ratio = 1.97 to 11.89), clinical benefit rate (odds ratio = 2.05 to 7.77), and duration of response with talazoparib in all subgroups. PROs in HR+/HER2− and TNBC subgroups showed consistent overall improvement and delay in time to definitive clinically meaningful deterioration with talazoparib vs PCT. Across subgroups, common adverse events included anemia, fatigue, and nausea with talazoparib and neutropenia, fatigue, and nausea with PCT. Seven patients (2.4%) receiving talazoparib had grade II alopecia and 22.7% had grade I alopecia. Across all patient subgroups with gBRCA-mutated advanced breast cancer, talazoparib demonstrated clinically significant superiority in outcomes compared with PCT.

1071 Background: The PARP inhibitor TALA was approved in the US for treatment of g BRCA-mutated ABC based in part on the EMBRACA study. Understanding the outcomes of EMBRACA pts relative to prior CT is a current unmet need. Methods: EMBRACA was a randomized Phase 3 trial comparing TALA 1 mg daily vs PCT (capecitabine, eribulin, gemcitabine, vinorelbine) in g BRCA-mutated ABC. Clinical outcomes were assessed by line of prior CT for ABC in intent-to-treat (ITT), triple-negative breast cancer (TNBC), and hormone receptor-positive (HR+) breast cancer cohorts. Results: 431 pts were randomized (ITT; TALA 287; PCT: 144). TALA was generally more effective than PCT across efficacy endpoints regardless of line of CT (Table). For the ITT population, TALA improved progression-free survival (PFS) and objective response rate (ORR) vs PCT for each line of CT assessed. Other prespecified subgroups (TNBC and HR+) will be presented. Conclusions: In pts with g BRCA-mutated ABC, TALA demonstrated improvements in clinical outcomes compared with PCT regardless of prior lines of CT. Clinical trial information: NCT01945775. [Table: see text]