Background

The ANNOUNCE trial evaluated the efficacy of the anti-PDGFR alpha antibody olaratumab + dox versus placebo + dox in adults with STS. CT was a secondary safety objective.

Methods

Treatment included dox 75mg/m² on Day 1 of a 21-day cycle for up to 8 cycles, with olaratumab/placebo on Days 1, 8 until progression. Use of the cardioprotectant dexrazoxane was allowed with any cycle and recommended with Cycle 5 and beyond. Pts were monitored for left ventricular ejection fraction (LVEF) decreases after 4, 6, 8 cycles and electrocardiogram (ECG) changes in cycles 1 to 9; both were then monitored every 3 months for 1 year, every 6 months for 1 year, then annually. Eligible pts had a LVEF of ≥ 50% at baseline, and were without QTc prolongation, active symptoms of cardiac arrhythmia/dysfunction, and prior anthracycline exposure or mediastinal/pericardial radiation.

Results

Median age was 57 years. Medical history included cardiac disorders (n = 33; 6.5%) and ECG abnormalities (n = 1; 0.2%). Of the 506 treated pts from both arms, 504 (99.6%) had at least 1 dox dose, of which, 64.0% received at least 1 dose of dexrazoxane, with 61.0% of these pts starting before Cycle 6. Median dox exposure was 6 cycles/450mg/m²; median duration of CT evaluation was 28 weeks. One pt died due to acute cardiac failure after a cumulative dox dose of 441mg/m². Adverse events (AEs) of cardiac dysfunction/decreased LVEF are summarized (Table). ECG abnormalities considered AEs occurred in 15 (3.0%) pts.Table:

1671O

Conclusions

The ANNOUNCE trial prospectively evaluated CT in a large cohort of dox-treated adults with STS, most of whom received dexrazoxane for cardioprotection. Although LVEF decreases were common with routine monitoring, symptomatic cardiac dysfunction was reported infrequently. Frequency of CT was similar in both arms. Longer safety follow-up may be warranted to determine the true rate of CT with higher cumulative doses of dox.

Clinical trial identification

NCT02451943.

Editorial acknowledgement

Karen Paulsrud, RPh, with Eli Lilly and Company, provided medical writing support.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

R.L. Jones: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Clinigen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Epizyme; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Deciphera; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Eli Lilly and Company; Advisory / Consultancy: Merck; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Tracon. A.J. Wagner: Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly and Company; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Five Prime; Advisory / Consultancy: Nanocarrier; Honoraria (self): Novartis; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Aadi Bioscience; Research grant / Funding (institution): Karyopharm. A. Kawai: Honoraria (self), Advisory / Consultancy: Eli Lilly and Company. A. Shahir: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. V. Soldatenkova: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. J. Wright: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. W.D. Tap: Shareholder / Stockholder / Stock options: Certis Oncology Solutions; Shareholder / Stockholder / Stock options: Atropos Therapeutics; Honoraria (self), Advisory / Consultancy: Eli Lilly and Company; Honoraria (self), Advisory / Consultancy: EMD Serono; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Immune Design; Honoraria (self), Advisory / Consultancy: Adaptimmune; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Blueprint; Honoraria (self), Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Agios Pharmaceuticals; Honoraria (self), Advisory / Consultancy: NannoCarrier; Advisory / Consultancy: Plexxikon Pharmaceuticals; Licensing / Royalties: Companion Diagnostic for CDK4 inhibitors; Officer / Board of Directors, Editor in Chief: Sarcoma Journal; Officer / Board of Directors, Treasurer: Connective Tissue Oncology Society.

Background

Clinical trials, focusing on selected pts, may have underestimated toxicities in cases with advanced age and co-morbidities, that are common in RW practice. Furthermore, clinical trials do not provide extended F/U. Thus, we assessed acute and long-term SCEs after adjuvant T in a large/unselected BC pt population.

Methods

Using healthcare administrative database, ie clinical discharge records and drug prescriptions of the Lombardy region (Italy), we selected pts newly diagnosed with early BC between 01/2008 and 12/2011 and monitored until 12/2016. Pts treated with T were 1:2 matched with pts treated with chemotherapy only for age, date of treatment, and cardiovascular risk factors. SCEs included heart failure and cardiomyopathy based on ICD9-CM codes. The cumulative risk of SCEs was estimated using the Kaplan-Meier method; independent predictors were assessed by the Cox regression model.

Results

Of a cohort of 34,218 pts with incident BC, 2,809 pts treated with T were matched to 5,618 pts treated with chemotherapy only. One SCE during F/U was experienced in 52 (1.8%) of T-users and 88 (0.26%) of non-T users. No cardiac death occurred. The 1-year cumulative risk of SCEs was 0.96%, with 1/4 of SCEs occurring within the first 6 months, in T-users, and 0.16% in non T-users. However, the T-user excess risk disappeared after 1 year of T. Thus, the hazard ratio [HR] was 9.96 (95%CI 3-78-26.2) during the first year, and 1.41 (95%CI 0.99-2.02) during the entire F/U period. HR was higher in the elderly, age>70 years, 8.77 (95%CI 5.25-14.64), and in pts with at least one pre-existing CRFs 2.32 (95%CI 1.68-3.22).

Conclusions

In RW practice, SCEs during/after T are infrequent, early and self-limiting. Based on the timeline of SCEs, it might be unnecessary to monitor cardiac toxicity beyond the period of T treatment. Besides, to reduce the excess of cardiac risk of the first year, strategies including shortening T exposure or increasing the number of check-ups in asymptomatic pts should be accompanied by the development of biomarker(s) able to identify pts at risk before/immediately after T initiation.

Legal entity responsible for the study

Serena Di Cosimo.

Funding

Associazione Italiana per la Ricerca sul Cancro (AIRC).

Disclosure

S. Di Cosimo: Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Teva; Advisory / Consultancy: EpiOnpharma; Advisory / Consultancy: Bayer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: GSK; Travel / Accommodation / Expenses: Celgene. All other authors have declared no conflicts of interest.

Background

The EPIPHANY decision tree is the first algorithm developed to predict serious complications in patients with cancer and pulmonary embolism (PE) (PMID: 28267709).

Methods

The objective is to evaluate the discriminatory ability of EPIPHANY in a prospective multicenter cohort. Patients with PE diagnosed by objective methods were recruited from October 2017 to April 2019. The association between the increase in prognostic category and in complications at 15 days was assessed using the linear by linear association test.

Results

The sample contains 463 patients with PE (39.7% suspected and 60.3% unsuspected). 68.3% (n = 316) showed clinical or haemodynamic instability, while 31.7% (n = 147) were normotensive PE with apparent clinical stability. The breakdown of initial risk criteria is: sudden or progressive dyspnea (58.7%), tachycardia >110 lpm (17.3%), hypotension <100 mmHg (9.9%), hypoxemia <90% (11%), elevated haemorrhagic risk (18.6%), tachypnea >30 rpm (3.2%), thrombopenia < 50000 (2.2%) and major bleeding (0.9%). Based on the entire decision tree, 21.8% were classified as low (n = 101), 22% as intermediate (n = 102), and 56.15% as high risk (n = 260). The serious complications rate at 15 days increased significantly throughout these prognostic categories: 3%, 5.9% and 26.5%, for low, intermediate and high-risk patients, respectively (p = 0.001). Serious complications occurred in 16.8% (n = 78) after a median of 5 days, being the most frequent: respiratory failure (56.4%), major bleeding (21.8%) and hypotension (20.5%). 28 patients died within the first 15 days post-PE, of which 2 belonged to the medium- and 26 to the high-risk group. The 3 main etiologies of exitus were: mixed origin (57.1%), complications of PE (32.1%) and progression of cancer (28.1%).

Conclusions

EPIPHANY is the only model available for the classification of patients with cancer and PE, based on their short-term risk of complications, with potential implications for decision making.

Legal entity responsible for the study

Asociación de Investigación de la Enfermedad Tromboembólica Venosa de la Región de Murcia.

Funding

Leo Academy.

Disclosure

M. Sanchez Canovas: Research grant / Funding (institution): Leo Pharma. All other authors have declared no conflicts of interest.

Background

The available options to manage cancer-associated anorexia-cachexia syndrome (CACS) are limited. At standard doses, the tetracyclic antidepressant mirtazapine causes appetite stimulation and weight gain. Based on limited evidence, it is used in cancer-associated anorexia. This trial was conducted to assess the efficacy and safety of mirtazapine in patients with CACS.

Methods

A double-blind randomized placebo-controlled trial. Included patients were adults with advanced solid tumors, weight loss ≥5%, appetite loss score ≥ 4 on 0 to 10 scale (10 = maximum appetite loss), and depression ≤3 on 0 to 6 scale (6 = extreme feelings of depression). Patients were randomized to receive mirtazapine 15 mg /day or placebo. The primary end-point was the change in appetite on a 0 to 10 appetite scale (where 10 is the best appetite possible) at week 4. Other assessed outcomes included changes in body weight, lean body mass, handgrip strength, depression (measured by the Hospital Anxiety and Depression Scale [HADS]), and quality of life (measured by Functional Assessment of Anorexia/Cachexia Therapy [FAACT] questionnaire).

Results

From 120 allocated patients, 100 completed 4 weeks treatment (48 in the mirtazapine arm and 52 in the placebo). After 4 weeks of treatment there was no significant difference between the two arms in the change from baseline in appetite or other outcome measures (Table 1). The change in the HADS depression score differed significantly in favour of mirtazapine. Sleepiness was significantly more prevalent in the mirtazapine arm (p = 0.01) and only one patient discontinued treatment due to excess sleepiness.Table: LBA86

Change in outcome measures from baseline to day 28

Conclusions

Compared to placebo, mirtazapine 15mg at night did not improve appetite, body weight, hand-grip strength or quality of life in advanced cancer patients with anorexia cachexia.

Clinical trial identification

NCT03254173.

Legal entity responsible for the study

The authors.

Funding

Cairo University.

Disclosure

All authors have declared no conflicts of interest.

Background

Adjuvant endocrine therapy (AET) is an oral medication prescribed to women with hormone-sensitive breast cancer (BC). AET is recommended daily for at least 5 years to reduce recurrence and mortality risks. Studies showed that a high proportion of women do not take daily or do not persist with AET for the recommended duration. The objectives of this study were to identify: 1) AET adherence trajectories for the 5 years following AET initiation among women diagnosed with non-metastatic BC and 2) factors associated with these trajectories.

Methods

We used data from the French Cohorte Cancer which includes data on hospitalizations, ambulatory care and medication claims for all cancer cases diagnosed in metropolitan France (SNDS database) . Women diagnosed with a first non-metastatic BC in 2011 and who had ≥1 AET claim in the 12 months after surgery were included in this study. For each woman, we estimated the proportion of days covered (PDC) by an AET for each month in the 5 years after AET initiation. Monthly PDCs were used to model AET adherence trajectories using Group-based trajectory modeling (GBTM). Statistical criteria were used to select the number of trajectories and evaluate the adequacy of the selected model. Factors associated with trajectories were identified using multinomial logistic regressions comparing.

Results

33 260 women were included. A 6-trajectory model wasselected: 1) 6.6% stopped the treatment by the end of the first year of treatment, 2) 5.7% declined adherence around half-term treatment 3) 6.3% after around 3 years, 4) and 8.3% after 4 years, 5) adherence varied between 50% and 60% without ever stopping for 4.3% of women and 6) 68.8% had an optimal adherence over the whole duration of treatment. Factors associated with trajectories included age, switch of molecule of AET during the treatment and the type of surgery.

Conclusions

To our knowledge, this is the first nationwide study to describe 5-year AET adherence trajectories. By identifying the timing of AET decline and/or cessation and factors associated with longitudinal adherence patterns, results could guide the development of interventions aimed at supporting women having an AET.

Legal entity responsible for the study

Institut National du Cancer (INCa).

Funding

INCa.

Disclosure

All authors have declared no conflicts of interest.