Mohammed Ibrahim

Background: Granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, are associated with bone pain, potentially impacting treatment adherence. This study hypothesized that a 5-day regimen of filgrastim would result in less bone pain than single-dose pegfilgrastim in patients receiving chemotherapy for early breast cancer. Methods: In this multicenter, open-label, randomized controlled trial, patients requiring prophylactic G-CSF during chemotherapy were randomly assigned 1:1 to receive either 5-day filgrastim or pegfilgrastim. The primary outcome was patient-reported bone pain, assessed as area under the curve of daily pain scores (0 = no pain to 10 = worst pain) over the first 5 days following G-CSF in cycle 1. Secondary outcomes included bone pain in cycles 2-4, febrile neutropenia, hospitalizations, chemotherapy delays, dose reductions, early discontinuations, chemotherapy-related deaths, health-related quality of life, and health-care resource utilization. Results: From June 2021 to March 2023, a total of 233 patients were randomly assigned, with 219 analyzed (110 filgrastim and 109 pegfilgrastim) after excluding those who withdrew before receiving treatment. Adjusting for stratification factors and prespecified baseline covariates using repeated measures linear regression, the mean area under the curve (0-40) for cycle 1 bone pain was 10.2 (11.2) for 5-day filgrastim and 10.2 (9.81) for pegfilgrastim, with an adjusted mean difference of 0.70 (95% confidence interval = 1.62 to 3.02; P = .556). Although no clinically significant differences were observed in most secondary outcomes, the 5-day filgrastim group exhibited a numerically higher incidence of febrile neutropenia (6.4% vs 0.9%, P = .065) and hospitalization (10.0% vs 3.7%, P = .106). Conclusion: There was no significant difference in bone pain between 5-day filgrastim and pegfilgrastim.

For early-stage hormone receptor (HR)-positive and HER2-negative breast cancer, tools to estimate treatment benefit include free and publicly available algorithms (e.g., PREDICT 2.1) and expensive molecular assays (e.g., Oncotype DX). There remains a need to identify patients who de-rive the most benefit from molecular assays and where this test may be of poor value. In this multicenter prospective cohort study, we evaluated whether use of PREDICT 2.1 would impact physician decision making. For the first 6 months of the study, data on physician use of both PREDICT 2.1 and Oncotype DX ordering were collected on all newly diagnosed patients eligible for molecular testing. After 6 months, an educational intervention was undertaken to see if providing physicians with PREDICT 2.1 results affects the frequency of Oncotype DX requests. A total of 602 patients across six cancer centers in Ontario, Canada were recruited between March 2020 and November 2021. Providing PREDICT 2.1 results and an educational intervention did not alter the ordering of an Oncotype DX. For patients with low clinical risk, either by clinico-pathologic features or by PREDICT 2.1, the probability of obtaining a high Oncotype DX recurrence score was substantially lower compared to patients with high-clinical-risk disease. The introduction of an educational intervention had no impact on molecular assay requests. However, routine ordering of molecular assays for patients with low-clinical-risk disease is of poor value.

Background: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. Methods: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. Secondary outcomes: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. Results: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were −4 (−10, −1) vs. −6.5 (−15, −2) for TC-H and P-H arms, respectively. Conclusions: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens.