Retrospective Analysis of Clinical Outcomes Associated With the Use of Pegfilgrastim On-body Injector in Patients Receiving Chemotherapy Requiring Granulocyte Colony-Stimulating Factor Support

Abstract

Objectives: Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) used as primary prophylaxis in patients receiving myelosuppressive chemotherapy regimens that have greater than 20% risk of developing febrile neutropenia (FN). Historically, pegfilgrastim has been administered 24 to 72 hours after chemotherapy, necessitating a return to clinic to receive the provider-administered injection. An alternative option is the pegfilgrastim on-body injector (OBI). With the OBI device, patients have their pegfilgrastim administered 27 hours after receiving chemotherapy while remaining at home, avoiding an additional clinic appointment. Concerns with pegfilgrastim OBI include lack of experience with the device in both the patient and provider, device-related failures, and the success of delivery. This study evaluates pegfilgrastim OBI failure rates through associated patient outcomes among cancer patients receiving chemotherapy requiring G-CSF. Methods: A retrospective electronic chart review was conducted of adult patients with cancer who received chemotherapy and pegfilgrastim OBI from July 1, 2016, to July 31, 2018. The primary objective of this study was the incidence of FN in patients receiving pegfilgrastim OBI. Results: There were no reported cases of hospitalization due to FN in patients who received pegfilgrastim OBI. Dose delays and dosage modifications were not observed in our review. The OBI device failure rate was found to be low (1.92%). Conclusion: The low device failure rate from this study suggests that the OBI is a viable option for administration of pegfilgrastim in patients receiving chemotherapy requiring G-CSF.

Introduction

Febrile neutropenia (FN) is a serious and life-threatening complication of chemotherapy that can adversely affect treatment outcomes by leading to treatment delays, chemotherapy dose reductions, morbidity, and mortality. This is especially significant when the desired goal is cure.^1,2 FN is defined as having a fever greater than 101°F (38.3°C) or a temperature of greater than or equal to 100.4°F (38.0°C) sustained over 1 hour with an absolute neutrophil count less than or equal to 500 cells/mL, or less than or equal to 1000 cells/mL with a predicted nadir less than or equal to 500 cells/mL.¹ Granulocyte colony-stimulating factors (G-CSF), such as filgrastim and pegfilgrastim, are used as primary prophylaxis for FN in patients who have greater than or equal to 20% risk for developing FN based on the myelosuppressive chemotherapy regimen being administered.³ Patient-specific risk factors such as prior chemotherapy/radiation exposure, persistent neutropenia, bone marrow involvement by tumor, recent surgery/open wounds, liver/renal dysfunction, and age above 65 years receiving full dose intensity also influence whether G-CSF is used as primary prophylaxis for FN.³ Pegfilgrastim can be administered subcutaneously via a standard injection (INJ) or through a delayed-release on-body injector (OBI). Yang et al demonstrated comparable pharmacokinetic and safety profiles between OBI and INJ pegfilgrastim; either administration method may be considered for FN prophylaxis.⁴

Standard pegfilgrastim INJ is administered 24 to 72 hours after the completion of myelosuppressive chemotherapy.⁵ Same-day administration of pegfilgrastim INJ has the potential to increase the risk for neutropenia by increasing the sensitivity of the rapidly dividing myeloid cells to chemotherapy. The OBI has been thought to provide an advantage by eliminating the need to return to clinic the day after chemotherapy.⁴ Pegfilgrastim OBI is a battery-powered, disposable, single-use timed injector that is placed on the patient’s abdomen or on the back of the upper arm.⁶ The device is manually filled with pegfilgrastim, activated by a healthcare provider, and applied to the patient on the day of chemotherapy immediately after the completion of chemotherapy. Twenty-seven hours after the OBI is activated, a single subcutaneous dose of pegfilgrastim 6 mg is delivered to the patient over a 45-minute duration.

Reasonable concerns with the use of pegfilgrastim OBI include reported device failures, questionable successful delivery of the medication, and inexperience with setting up the device. A device failure with pegfilgrastim OBI is an instance in which the device does not function as originally intended. Examples of this include drug leakage from the device, the indicator light flashing red after administration, the device indicator reading full after drug administration, and the device falling off the body of the patient prior to the administration of pegfilgrastim. Pegfilgrastim OBI has shown low failure rates (2%-3%) when administered by clinicians who have experience with the device.^7,8 Clinicians may have concerns with the device since no one from the health care team is present to witness pegfilgrastim administration with use of the OBI. Device failures that go unrecognized could lead to FN and treatment delays. Hauber et al conducted a survey of patients and physicians to assess preference of administration options between OBI and INJ pegfilgrastim.⁹ The survey reported that patients preferred receiving pegfilgrastim via an administration modality for which they had familiarity and experience. Although physicians in this survey noted that returning to clinic the following day for pegfilgrastim administration can be burdensome, preference for using INJ or OBI changed depending on the clinical status of the patient. Physicians were more likely to prefer the OBI method of pegfilgrastim administration when patients had to travel greater distances or were more clinically compromised.

Mahler et al reported successful implementation of OBI at their institution.⁸ The results were attributed to proper education of the staff and patients on the device. The pegfilgrastim OBI was shown to be safe and effective, had high patient satisfaction, and improved oncology nursing unit workflow. Despite the positive attributes noted with OBI in this study, it was also noted that 3% of patients had a device failure and 7% experienced FN. The objective of our study was to observe pegfilgrastim OBI failure rates through patient outcomes.

Methods

A retrospective chart review was conducted at a single medical oncology practice within a multi-site cancer center at our health system. This study was reviewed and approved by the institutional review board. Patients who received pegfilgrastim OBI between July 1, 2016, and July 31, 2018, were identified through a computer-generated report via our electronic medical record. Primary inclusion criteria for the study were patients above the age of 18 years old, pegfilgrastim administration via the OBI, and a diagnosis of a solid tumor malignancy receiving chemotherapy requiring growth factor support. Data collection included patient age, sex, ethnicity, cancer diagnosis, cancer stage, chemotherapy treatment intent, and regimen administered. Prior to a patient receiving the OBI device, nursing staff were educated and trained on the proper administration of pegfilgrastim OBI by the manufacturer.

The primary outcome was the development of FN. The FN was defined as a fever greater than 101°F (38.3°C), or greater than or equal to 100.4°F (38.0°C) sustained over 1 hour with an absolute neutrophil count less than or equal to 500 cells/mL, or less than or equal to 1000 cells/mL with a predicted nadir less than or equal to 500 cells/mL.¹ Secondary outcomes included pegfilgrastim OBI device failure and treatment delays or dose modifications secondary to FN or neutropenia. A device failure was defined as the OBI device not functioning as it is intended to function. Patients were followed for up to 30 days following the last administration of chemotherapy for the occurrence of any study endpoints. Descriptive statistics were used to determine the frequency of the device failing to deliver pegfilgrastim and the occurrence of FN.

Results

Twenty-eight patients met the eligibility criteria. A total of 104 doses of pegfilgrastim OBI were administered during the study period. Baseline patient demographics are described in Table 1. The median age was 56 years old (range 23-78), and 27 patients were female (96%). Twenty patients (71%) were Caucasian, and 7 patients (25%) were African American. A total of 25 patients (89%) had a diagnosis of breast cancer. Including all cancer diagnoses, 7 (25%), 13 (46%), and 6 (21%) patients had stage I, II, and III disease, respectively. The most common chemotherapy regimens used included TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab; n = 10 [35%]), TC (docetaxel, cyclophosphamide; n = 7 [25%]), and dose-dense AC (doxorubicin, cyclophosphamide; n = 7 [25%]). All patients had received pegfilgrastim OBI as primary prophylaxis against FN.

Table 1.

Baseline Patient Demographics (N = 28).

Median age, y (range)	56 (23-78)
Female sex	27 (96.43%)
Ethnicity
Caucasian	20 (71.43%)
African American	7 (25.00%)
Asian	1 (3.57%)
Cancer diagnosis
Breast cancer	25 (89.29%)
Prostate cancer	1 (3.57%)
Endometrial cancer	1 (3.57%)
Lymphoma	1 (3.57%)
Stage of malignancy
I	7 (25.00%)
II	13 (46.43%)
III	6 (21.43%)
IV	2 (7.14%)
Treatment intent
Curative	26 (92.86%)
Palliative	2 (7.14%)
Chemotherapy regimen
Dose-dense AC	7 (25.00%)
TC	7 (25.00%)
TCHP	10 (35.71%)
Othera	4 (14.29%)

Note. AC = doxorubicin, cyclophosphamide; TC = docetaxel, cyclophosphamide; TCHP = docetaxel, carboplatin, trastuzumab, pertuzumab.

^aOther regimens included trastuzumab, pertuzumab, docetaxel (n = 1); carboplatin, paclitaxel (n = 1); cabazitaxel (n = 1); and doxorubicin, vincristine, cyclophosphamide, rituximab, prednisone (n = 1).

None of the patients in our study developed FN. There were also no treatment delays or chemotherapy dose modifications secondary to an FN event or neutropenia. Two device failures occurred (1.92%). One patient experienced a malfunction of the device indicator light, but after speaking to technical support it was believed the patient received the full dose. No complications suggestive of a missed dose occurred. The second patient experienced an injection malfunction. The pegfilgrastim dose was not delivered properly, and it was reported the pegfilgrastim leaked down the patient’s arm. The patient returned to clinic without any further complications reported and received pegfilgrastim INJ. It was unclear as to why this device failure occurred.

One instance of anaphylaxis was reported after receiving pegfilgrastim OBI. Within 15 minutes of receiving the injection, the patient experienced throat swelling, shortness of breath, and abdominal pain. The pegfilgrastim OBI was discontinued and the patient received filgrastim instead for the remainder of their treatment regimen without any complications.

Discussion

While previous studies have reported safety and efficacy of OBI, this study would be the first to look at the pegfilgrastim OBI failure rates through patient outcomes. The OBI has the potential to benefit both patients and the clinical staff. Pegfilgrastim OBI can decrease the number of trips to the infusion center and reduce travel time and cost associated with care for patients. Nursing time can be decreased by eliminating an additional clinic appointment the day following chemotherapy. With the pegfilgrastim INJ, there is an additional clinic visit appointment on top of a chemotherapy infusion appointment. Pegfilgrastim OBI does not require this additional time and clinic occupancy, thus relieving time from nursing.

Strengths to the present study include taking place in a real-world setting as well as documentation of OBI patient education. Education included signs that the device may be malfunctioning and when to contact the provider. Both verbal and written communication was provided to patients before receiving pegfilgrastim OBI. Well-trained and experienced staff are vital when using the OBI device. Our nursing staff had been educated and trained on the proper administration of pegfilgrastim OBI by the manufacturer prior to any patient receiving the medication. The education provided to both patients and staff may have played a role in promptly identifying the two device failures we noted in our study.

Limitations to our study include small sample size, retrospective study design, and lack of comparison in neutropenia-associated outcomes with pegfilgrastim INJ. With a retrospective design, OBI failures could have occurred without patients reporting it. Another limitation worth noting is our study patient population. Our patient population included mostly young women with breast cancer who had private insurance. Males, elderly patients, non–breast cancer malignancies, and those of a lower socioeconomic status were underrepresented in our study. Our limited patient population could have contributed to both the low device failure rate in our experience as well as our device failure rates being lower than in other studies.^7,8 Future studies with more diverse patient populations are needed. With our study being a single-center evaluation, it is possible that patients could have been hospitalized for an FN event at an outside facility, and this data may have not been captured. However, no documentation in any follow-up physician notes regarding any FN events that occurred outside of our facility were recognized in our chart review.

This study evaluated patient-reported outcomes. Patient and nurse satisfaction data were not collected. Patient and nursing perspectives would be useful to evaluate when assessing the benefit of using a new method of administration for a medication. Future research should include prospective studies, patient satisfaction surveys, nurse satisfaction surveys, and the impact on infusion clinic workflow. By gathering these data, it may further influence the clinical uses of the OBI.

Conclusions

This is one of the first studies to look at pegfilgrastim OBI in relation to patient outcomes. Approximately 98% of administrations of pegfilgrastim OBI were successful. There were no occurrences of FN or treatment delays. With the low failure rate observed in this study and, to the best of our knowledge, no obvious unreported failures, pegfilgrastim OBI continues to be a viable option that may enhance patient convenience for those receiving chemotherapy requiring G-CSF. Future studies are needed to evaluate patient, nurse, and physician satisfaction with the pegfilgrastim OBI. Large, multicenter studies are also needed to obtain more data regarding OBI failures and clinical outcomes. A cost–benefit analysis may also be needed in the future when comparing the price of the OBI to the standard injection when considering chair time, specialty pharmacy involvement, patient travel, and other potential variables.