Satisfaction with injection experience of patients with neuroendocrine tumors enrolled on lanreotide autogel patient support programs: Results from the international HomeLAN survey

Lanreotide autogel/depot (LAN) is a somatostatin analog used in first‐line treatment for neuroendocrine tumors (NETs). The aim of HomeLAN was to evaluate the satisfaction with injection experience among patients with NETs receiving at‐home LAN injection via patient support programs (PSPs). This was an international, non‐interventional, cross‐sectional, online survey in adults with NETs enrolled in PSPs, receiving LAN injections at home, administered by a healthcare professional (HCP) or administered independently (self or caregiver administering injection). The primary endpoint was satisfaction with the most recent LAN injection. Secondary endpoints included the level of anxiety prior to injection, impact on daily life, and the extents to which participants felt in control of their life and agreed that home administration met their medical needs. In total, 111 participants from Belgium, Greece, the Netherlands, and Spain completed the survey (50.5% male; mean age, 63.6 years; most common primary tumor site was intestine [47.7%]). For 99 participants, their most recent injection was administered by an HCP. Overall, 95.5% of all participants were satisfied with their most recent injection experience (95% confidence interval: 89.89%–98.06%); 67% reported experiencing no anxiety prior to injection, 91.0% reported that home injection had a “great deal” or “quite a bit” of positive impact on their daily life, and 85.6% strongly agreed that the PSP met their medical needs. In the HCP injection subgroup, 71.7% reported that this mode of administration helped them to feel in control of their lives. In this patient survey, satisfaction levels were high among patients with NETs receiving LAN injections at home via a LAN PSP. Most patients did not experience anxiety prior to their most recent injection and acknowledged that thanks to their treatment they had a good quality of life despite their disease. Most strongly agreed that the PSP met their medical needs, which highlights the valuable service that LAN PSPs provide for patients with NETs.


| INTRODUCTION
Somatostatin analogs are the mainstay of first-line medical treatment for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). [1][2][3] Lanreotide autogel/depot (LAN) is licensed to treat grade 1 and grade 2 GEP NETs of midgut, pancreatic, or unknown origin with a Ki-67 score under 10%, based on its antiproliferative efficacy in enteropancreatic NETs demonstrated in the phase III CLARINET study. 4 LAN is presented as a prefilled, ready-to-use syringe, and is given as a once-monthly deep subcutaneous injection. The syringe was redesigned in collaboration with patients, caregivers, and healthcare professionals (HCPs) to generate a device that was more ergonomic and more user-friendly than the previous version. 5 The redesigned syringe has been approved in many countries and has largely replaced the former LAN syringe.
Because NETs require long-term treatment, 6 easy and efficient treatment delivery is important to optimize outcomes, as is adopting a patient-centered approach to management and empowering patients to engage in self-management, including by providing the option of home administration and, when approved, independent injection. 7 LAN is licensed in several countries for independent injection (i.e., administered by the patient or a caregiver). Independent injection is available for patients receiving a stable dose and is based on HCP decision and after appropriate training by an HCP. Therefore, as well as providing an at-home injection service by HCPs, LAN PSPs can include an injection training service. A randomized crossover study performed with the former LAN syringe in 25 patients with NETs showed that independent injection did not affect efficacy (symptoms and biochemical control) or safety of LAN when compared with administration by an HCP. Furthermore, most patients in the study preferred independent injection. 9 The aim of the current survey (HomeLAN) was to evaluate satisfaction with their most recent injection experience among patients enrolled in medically led LAN PSPs.

| Study design and participant population
HomeLAN was an international, non-interventional, cross-sectional, online survey, conducted between July and November 2021. Participants were enrolled from a number of European countries with medically led LAN PSPs, with more than 50 patients with NETs using the program. Five countries were intended to participate: Belgium, Germany, Greece, the Netherlands, and Spain, with the survey launched in four of them.
Participants were initially recruited electronically via an invitation (in the local language) sent by the PSP vendors. Patients were eligible for inclusion if they were aged 18 years or older, had diagnosed NETs, were enrolled in a medically led LAN PSP for 6 months or more, and were receiving treatment with LAN at home. The inclusion criteria did not stipulate a minimum treatment duration prior to enrolment in the PSP. All participants provided informed consent electronically before data collection.

| Endpoints
The primary endpoint was the percentage of participants who reported being satisfied with their most recent LAN injection. Secondary endpoints evaluated participants' injection experience (irrespective of who performed the injection) and their experience of injection administered by an HCP or independently (by the participant or caregiver) ( Table 1). Injection experience endpoints included the level of anxiety prior to the most recent injection, the extent to which LAN injection at home made participants feel that they were in control of their lives, how it positively impacts on daily life, whether the home administration program met their medical needs, and the impact of home injection on participants' quality of life. Injection by HCP endpoints included reasons for not choosing independent injection and willingness to change to independent injection. The survey was also intended to generate data on potential time and cost savings associated with treatment at home compared with previous clinic-based treatment. However, owing to the high proportion of participants who responded "Don't know" (as high as 70% for some questions) and the large proportion of missing data (as high as 45% for some questions), it was not possible to analyze these variables.

| Online survey
The survey was drafted by the sponsor based on the endpoints identified, and then reviewed by an expert in patient-reported outcomes and by the HomeLAN study steering committee. A cognitive debriefing of the English version of the survey was then performed by the Contract Research Organization conducting the survey with two patients with NETs who were native English speakers. The final version of the English-language survey was translated into the local languages of the participating countries. Respondents were asked to provide the name of their treating facility and the city in which it was located to confirm eligibility; quality control checks of this information were conducted on one-third of the completed surveys. The time taken to complete the survey and potential duplicates on key variables were also checked as part of the quality control step.
Participants who commenced the survey but did not complete it were not included in the analysis.

| Sample size and statistical analysis
Based on an initial target of five PSPs including 800 patients with NETs, it was estimated that 120 would respond to the survey (15% response rate). To prevent over-representation of specific countries, it was planned to close the survey in each country once 50 surveys had been completed.
For the primary endpoint, the proportion of participants who reported being satisfied with their most recent injection experience was summarized, overall and by mode of administration (HCP or independent injection). The corresponding 95% confidence intervals (CIs) were calculated. All secondary endpoints were analyzed descriptively.
Statistical analyses were performed using software R (version 4.1.0, or more recent).

| Participant demographics and clinical characteristics
Overall, 153 individuals from four countries were screened and 135 met the eligibility criteria. In total, 111 participants fully completed the survey with no quality control issues (Belgium, n = 30; Greece, n = 13; the Netherlands, n = 45; Spain, n = 23); 62.2% had been enrolled in PSPs for more than 2 years ( Table 2). The largest proportion of patients in each country had been enrolled on the PSP for over 2 years except for Spain, where the program was the most recently established. Overall, 50.5% of participants were male, the mean (± standard deviation) age was 63.6 (± 10.7) years and 65.8% were older than 60 years. Median (95% CI) time since diagnosis was 4.0 (3.02-4.98) years, and the primary tumor site was in the intestine in 47.7% of participants and the pancreas in 26.1% of participants (Table 2). In 99 participants (89.2%), the most recent LAN injection had been administered by an HCP; 12 participants (10.8%) had received their most recent LAN injection via independent injection, therefore, considering the small sample size in this subgroup, results should be interpreted cautiously.

| Primary endpoint (satisfaction with most recent injection experience)
Overall, 95.5% of all participants were satisfied with their most recent injection experience (95% CI: 89.89-98.06%) ( Figure 1). In those who received injection by HCP, 95 participants (96.0%) were satisfied, one was somewhat dissatisfied, and three were very dissatisfied. Of the participants who had injected independently, 11 out of 12 were satisfied, one was somewhat dissatisfied, and none were very dissatisfied with their most recent injection experience.

| Injection experience
Over two-thirds of all participants (67.6%) reported not feeling anxious prior to their most recent injection; this value was 70.7% in those injected by HCP ( Figure 2). No anxiety was reported by five of the 12 participants in the independent injection subgroup.
Overall, 71.7% of participants in the HCP injection subgroup reported that this mode of administration helped them to feel in control of their lives "A great deal" (n = 19) or "Quite a bit" (n = 52) ( Figure 3). In the independent injection subgroup, six participants reported feeling "A great deal" of control over their life, and two reported feeling "Quite a bit" of control over their life. value in the injection by HCP subgroup was 49.5% (Table S1). Eight participants in the independent injection subgroup reported that home injection had "A great deal" of positive impact.
For most participants (90%), thanks to their treatment, they reported a good quality of life despite their illness, and all agreed they felt comfortable talking to their HCP about their health problems (Table S2).
Over two-thirds (71.1%) of participants indicated that they either had "normal activity, and no symptoms" or "some symptoms, but they do not require that I rest during the day". In contrast, only seven participants felt their condition "requires me to rest for more than 50% of the day" and none reported being unable to get out of bed.

| Reasons for choosing HCP injection
The most common reasons selected for participants to choose HCP injection rather than independent injection are shown in Figure 4.
Overall, 94.9% of the participants stated that they would not be willing to change to independent injection. Of the five who would be willing, only one reported having received training on independent injection.

| Reasons for choosing independent injection
The most common responses selected as reasons for participants to choose independent injection rather than HCP injection were "Feels more independent" (n = 6), "Easier to do" (n = 5), and "Gives me flexibility" (n = 4). Seven participants had initiated independent injection before the COVID-19 pandemic and five during the pandemic. Of these five participants, only two reported that they would continue independent injections after the pandemic. All participants agreed that they had a clear idea about how to manage their injections.

| DISCUSSION
For patients requiring long-term treatment, it is important to consider their overall treatment experience to minimize any negative impact on their life and maximize treatment adherence. 7,8 Indeed, the importance of considering the needs of those who will be using medical products was specifically highlighted in a study by Adelman et al., which showed that the LAN syringe could be improved to meet the needs of patients, caregivers, and nurses, while ensuring that LAN was delivered properly and safely. 5 Providing a service that allows patients to receive treatment at home is one potential way to improve their healthcare experience; home-based services were particularly important during the COVID-19 pandemic because they reduced patients' risk of exposure to the virus. 10 It remains to be seen whether an increase in this type of service will be maintained in the post- injections from an HCP. The most common reasons for choosing HCP injection rather than independent injection were lack of confidence that the injection would be performed correctly, lack of training on self-injection, the positive impact of the interaction with the nurse performing the injection, and their physician's preference for injection to be performed by a nurse. Furthermore, 95% of participants in the HCP injection subgroup would not be willing to change to independent injection. At-home HCP injection provides a combination of convenience (albeit not to the same extent as independent injection) and the reassurance of HCP interaction. The latter is particularly important (given the seriousness of the diagnosis) in reassuring patients that their treatment is being administered correctly.
Some participants indicated that their choice of HCP administration was influenced by the fear (14.1%) or the anxiety (11.1%) that could occur with independent injection, though out of all participants, only three reported that they felt "Very anxious" or "Extremely nience associated with self/caregiver administration. 13

DATA AVAILABILITY STATEMENT
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vivli.org for assessment by an independent scientific review board. Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

ETHICS STATEMENT
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