Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events.

BACKGROUND: Naxitamab is a humanized GD2-binding monoclonal antibody that received accelerated approval from the U.S. Food and Drug Administration for refractory or relapsed high-risk neuroblastoma limited to bone or bone marrow. Trial 201 (NCT03363373) is an ongoing global clinical trial to evaluate the efficacy and safety of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in this population. AIMS: Here, we review the safety profile and adverse event (AE) management associated with naxitamab administration in a pediatric population, based on Trial 201 protocol guidelines and clinical trial experience. METHODS AND RESULTS: At least 50% of patients experienced pain, hypotension, bronchospasm, cough, vomiting, diarrhea, nausea, and tachycardia, with the following reported at grade ≥3 AEs for at least 10% of patients: pain, hypotension, urticaria, and bronchospasm. These AEs were generally manageable in the outpatient setting using premedications, supportive therapies, and appropriate monitoring post-infusion. Algorithms were established for infusion-related AEs, including hypotension and bronchospasm, to provide guidance to investigators for early recognition and timely intervention, including medication and infusion rate modification or interruption, or treatment discontinuation, based on AE severity. Educating patients and caregivers on what to expect regarding premedication at home, experience during the infusion cycle, and post-infusion monitoring helps optimize naxitamab treatment and supportive therapies and may reduce treatment burden. CONCLUSION: This article highlights the protocol-based recommendations for the management of acute AEs associated with outpatient naxitamab treatment in Trial 201. The authors recommend close monitoring and timely implementation of measures to ensure that patients can remain on treatment and obtain maximum clinical benefit from naxitamab therapy.

Integrating online community support into outpatient breast cancer care: Mayo Clinic Connect online platform.

INTRODUCTION: Mayo Clinic Connect is an online community of over 100,000 members who support each other through sharing lived experience when facing and managing new diagnoses. The community is moderated by Mayo Clinic staff and volunteer patient mentors. METHODS: Mayo Clinic breast clinic patients undergoing evaluation received a binder of support resources including a brochure about Mayo Clinic Connect at visits between January and May of 2019. Surveys were distributed at subsequent visits between May and December of 2019 to assess patient awareness about the online resource, participation frequency, purpose of use, and benefits for members, as well as reasons for not joining (non-members). The primary aim was to assess patient resilience, coping, and self-management after joining the online community. RESULTS: Nine hundred surveys were distributed, and 102 participants completed surveys between May and December 2019. Forty-five percent (n = 46) had heard about Mayo Clinic Connect; 34% (n = 15) through a brochure. The remainder heard about the community from a Mayo Clinic provider (43%; n = 19) or other resources (22%, n = 10; no response n = 2). Twenty percent (n = 20) of survey participants registered as Breast Cancer group members, and most of this subgroup (55%; n = 11) reported understanding diagnosis, treatment plans, and finding peer support as reasons for joining. Seventy-five percent of Mayo Clinic Connect participants (n = 15) reported the community met or exceeded expectations. CONCLUSION: This pilot study reveals the potential positive impact of introducing an online peer support group into clinical care plans for patients coping with a new and anxiety-provoking cancer diagnosis.

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer.

BACKGROUND: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. PATIENTS AND METHODS: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2- MBC previously treated with chemotherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. RESULTS: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence interval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. CONCLUSIONS: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy.

A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer.

PURPOSE: The primary objective was to evaluate intracranial objective response rate (iORR) in patients receiving abemaciclib with brain or leptomeningeal metastases (LM) secondary to hormone receptor-positive (HR+) metastatic breast cancer (MBC). Secondary objectives evaluated extracranial response, abemaciclib pharmacokinetics, brain metastases tissue exposure, and safety. PATIENTS AND METHODS: This nonrandomized, phase II study (NCT02308020) enrolled patients in tumor subtype-specific cohorts A-D: A (HR+, HER2- MBC), B (HR+, HER2+ MBC), C (HR+ MBC LM), and D (brain metastases surgical resection). Abemaciclib 200 mg was administered twice daily as monotherapy or with endocrine therapy, or 150 mg twice daily with trastuzumab. Cohorts A and B used a Simon two-stage design. RESULTS: In cohort A (n = 58), 3 patients were confirmed responders resulting in an iORR of 5.2% [95% confidence interval (CI), 0.0-10.9], and the intracranial clinical benefit rate (iCBR) was 24% (95% CI, 13.1-35.2). Median overall survival (OS) was 12.5 months (95% CI, 9.3-16.4). A volumetric decrease in target intracranial lesions was experienced by 38% of patients. In cohort B (n = 27), there were no confirmed intracranial responses. An iCBR of 11% (95% CI, 0.0-23.0) was observed. Median OS was 10.1 months (95% CI, 4.2-14.3). A volumetric decrease in target intracranial lesions was experienced by 22% of patients. In cohort C (n = 10), one confirmed complete parenchymal response was observed. In cohort D (n = 9), unbound brain metastases concentrations of total active abemaciclib analytes were 96- [cyclin-dependent kinase 4 (CDK4)] and 19-fold (CDK6) above in vitro IC50. Safety was consistent with prior studies. CONCLUSIONS: This study did not meet its primary endpoint. Abemaciclib was associated with an iCBR of 24% in patients with heavily pretreated HR+, HER2- MBC. Abemaciclib achieved therapeutic concentrations in brain metastases tissue, far exceeding those necessary for CDK4 and CDK6 inhibition. Further studies are warranted, including assessing novel abemaciclib-based combinations.