The Khorana score was utilized to determine the baseline risk of venous thromboembolism (VTE) of patients in this safety analysis.2 The Khorana scoring system assigns one point (unless otherwise noted) for each of the following characteristics

• site of cancer 
  • high risk (1 point): lung, lymphoma, gynecologic, genitourinary (excluding prostate)
  • very high risk (2 points): stomach, pancreas
• platelet count of 350x10⁹/L or more
• hemoglobin <10g/dL and/or use of erythropoiesis-stimulating agents
• leukocyte count > 11x10⁹/L, and
• body mass index (BMI) >35 kg/m².3

Patients are divided into low risk (0 points), intermediate risk (1-2 points), and high risk (>3 points) based on the scoring system.3

In monarchE, the baseline Khorana risk score was well balanced across arms. Known risk factors (increased age and BMI) were also analyzed in patients experiencing VTE.2

The data and information presented in this document are from the primary outcome (PO) analysis, which includes 19.1 months of median follow up in both arms.4 At a later data cut with a median follow-up time of 27 months (Additional Follow-up 1 [AFU1] analysis), there were minimal increases in incidence of most frequently reported treatment-emergent adverse events, including VTE, in the abemaciclib + ET arm.5

At the primary outcome analysis, in patients treated with abemaciclib, most VTEs were grade >3 and primarily pulmonary embolism (PE) events, including 6 Grade 4 VTEs.6

Of the VTEs,

• 17 PEs had a serious outcome (e.g. hospitalization), and
• the remaining 9 PEs did not qualify as SAEs.6

The observed rate of VTEs was higher when tamoxifen, rather than AI, was administered as the initial ET.6

Risk factors for VTE were generally well-balanced across arms and around 94% patients who experienced VTEs received anti-coagulation therapy.6

Most VTEs (88.1%) were single occurrences. There were 8 patients that reported 2 episodes of VTE, including 5 patients with simultaneous VTE and PE. Only one patient had recurrent VTE after resuming abemaciclib.2

Most patients continued abemaciclib after a VTE,

• with 57% requiring a dose hold, and
• 19.4% discontinuing, mainly due to Grade >3 events.2

Approximately half of the VTE events occurred early on treatment in both arms, with a median time of onset of first VTE at approximately 6 months. In the abemaciclib arm, 47% experienced a VTE within the first 180 days, and 48% of PE events occurred within first 180 days.2

VTE events at the PO analysis are summarized in VTE Events in monarchE.

Other risk factors for patients reporting a VTE (abemaciclib vs. ET only, respectively) include

• central catheter use (22% vs. 50%)
• recent flight or recent period of immobility (25.4% vs. 18.8%), and
• 1 patient in the abemaciclib arm with a prior history of VTE.2

There was no correlation observed with incidence of VTE/PE and increasing age, but there was a trend for higher incidence of PE and Grade 3/4 VTE with increasing BMI, as seen in VTE Events by BMI in the Abemaciclib Arm (n=2791) of the monarchE trial.2

Overall, the majority of clinically significant VTE events occurred within the first 6 months; no cumulative effect or increased risk with longer treatment duration of abemaciclib was observed.2

VTE was managed per standard clinical practice and most patients experiencing VTE could continue abemaciclib treatment without further recurrence.2

For management of VTE events in monarchE, abemaciclib was held for 1-2 weeks and anticoagulation was started per local clinical practice. Patients taking tamoxifen were recommended to change ET therapy. Patients with a prior history of VTE were excluded.2

Dose reductions of abemaciclib were reported for 4 patients in the abemaciclib + ET arm and 38 patients had dose omissions in the abemaciclib + ET arm.5

Dose modification and management recommendations are summarized in Dose Modification and Management - VTEs.