2022 ENEA Breakthrough | the best solution for SRL monotherapy to manage patients with acromegaly throughout the process

2022 ENEA has released updated data from two real-world studies that included data from the US MarketScan^® claims database from January 1, 2010 to May 31, 2020, one of which evaluated the course of treatment of patients receiving medication, and the results showed that 94.
2% of patients (n=924) received first-line monotherapy at baseline and 51.
3% received first-generation SRL initially (n=381; lanreotide ATG [n=201] and/or octreotide LAR [n=195]), 80.
8% of patients did not change regimens throughout the study period1
.

Another further evaluation of drug dose and titration in patients with large limbs who received lanreotide ATG (n=155) or octreotide LAR (n=117) monotherapy showed that 69.
0% of patients treated with lanreotide ATG received a dose of 90 mg/month, and 70.
9% of patients receiving octreotide LAR received a dose of 20 mg/4 weeks (Table 1); The proportion of patients starting above the approved dose of lanreotide ATG (> 120 mg) was much lower than that of patients starting above the approved dose of octreotide LAR (> 30 mg) (1.
3 versus 12.
8 percent), and the proportion of patients receiving an increased dose of lanreotide ATG was also lower than that of patients increasing the dose of octreotide LAR (15.
5 versus 17.
1 percent) (Table 1), and the most common increased titration regimen for patients receiving lanreotide ATG was from 90 mg/4 weeks to 120 mg/4 weeks, from 20 mg/4 weeks to 30 mg/4 weeks for patients receiving octreotide LAR; The proportion of patients receiving lanreotide ATG extended dosing interval (EDI) regimen was higher than octreotide LAR EDI^* (7.
1% versus 4.
3%)²
.

Table 1.
Dose increases in patients with large limbs in the MarketScan^® database

These studies suggest the importance of determining the best treatment regimen at the beginning of treatment for the best long-term outcome, and that in the real world, first-generation SRLs are the most widely used drug regimen, in which the proportion and continuation of treatment with lanreotide ATG are higher than octreotide LAR¹, and the initial standard-dose lanreotide ATG monotherapy regimen can effectively manage patients with large limbs ²
。 So how can further treatment be developed for patients who cannot be controlled with SRL alone?

Increasing the dose / frequency of lanreotide ATG titration, IGF-I normalization can be achieved in 27.
6% of patients

Professor Maria Fleseriu of Oregon Health and Science University delivered a presentation
at the 2022 ENERA on the theme "Exploring Treatment Options for Acromegaly".
Professor Maria Fleseriu noted that increasing the dose or frequency of SRL is an important management regimen recommended by current guidelines for patients with uncontrolled limb augmentation ^{with monotherapy3}
.
A 24-week prospective, multicenter, randomized, open-label trial evaluated lanreotide ATG at a high dose (HD) (180 mg/4 weeks; n=15) and high frequency (HF) (120 mg/3 weeks; n=15) Dosing regimen^**, biochemical efficacy and safety in patients with active limb large who are partially in remission after standard-dose SRL treatment, results show (Figure 1)³:

➤ IGF-I levels decreased significantly after 24 weeks of treatment (P=0.
007), and the HD group (P=0.
03) decreased more than the HF group (P=0.
08)⁴;

➤ IGF-I levels normalized in 27.
6% of patients (P=0.
016 vs baseline), and there was no significant difference between HD and HF groups (P=0.
59);

➤ The safety profile was good, adverse events were mild to moderate and transient, and there was no difference
between HD and HF groups.

This study suggests that about one-third of patients with active limb augmentation who are not adequately controlled by long-term conventional SRLs can normalize
IGF-I levels with HD and HF lanreotide ATG regimens.

Figure 1.
HD and HF regimen treatment results

Lanreotide ATG EDI regimen can significantly reduce GH and IGF-1 levels, low cost, and improve treatment adherence

Professor Maria Fleseriu further pointed out that the European Congress of Endocrinology (2022 ECE) published a systematic literature review that provides an important reference
for the long-term management of patients with MPI by EDI regimens.
A total of nine studies of lanreotide ATG (≤ 1 time/4 weeks), 4 octreotide LAR (≤ 1 time/4 weeks), 3 pevisoman (once daily), 11 SRL (1 time/4 weeks) + pevisoman (≤ 1 time/day) combination therapy were included in this review, and the results showed (table 2):

➤ From baseline to the end of the study, IGF-1 levels generally decreased in all patients treated with EDI regimens;

➤ A generation of SSA drug EDI regimens can achieve significant GH reduction;

➤Lanreotide ATG EDI regimen can simultaneously achieve tumor shrinkage/no growth, health-related quality of life (HRQoL) improvement/maintenance, high treatment satisfaction, low treatment cost, and similar adverse event rates
to standard regimens.

This study suggests that both monotherapy and combined EDI regimens can significantly reduce IGF-1 levels, while lanreotide ATG monotherapy EDI regimens can significantly reduce GH levels, improve quality of life, improve treatment adherence, have good safety and reduce economic costs, and are the preferred EDI regimen
.

Table 2.
IGF-1 and GH results after EDI therapy

With a low-dose SRL+ weekly pevisoman regimen, IGF-I normalization can be achieved in 96% of patients at low cost

Professor Maria Fleseriu notes that SRL in combination with pevisoman is also a common regimen recommended by current guidelines for monotherapy in patients with uncontrolled limb ^megalopes3,5
。 A prospective, randomized, open-label study in a tertiary referral pituitary centre compared high-dose SRL (lanreotide ATG 120 mg / octreotide LAR 30 mg) + pevixoman (40-160 mg/week) once weekly (Group A; n=17), low-dose SRL (lanreotide ATG 60 mg/octreotide LAR 10 mg) + pevisoman once weekly (group B; n=23), low-dose SRL + pevisoman (15-60 mg/day) once daily (Group C; n=20) efficacy and cost-effectiveness of 3 regimens in patients with GPX with and without biochemical control, results ^showing3,5:

➤ IGF-I control was achieved with all three treatment options regardless of the response to SRL in patients with large limbs (Group A 93.
3%; Group B 95.
7%; Group C 100%);

➤ In terms of average monthly treatment costs, Group B ($9,837± $1,375) < Group A ($14,261± $1,645) and Group C ($22,543± $11,158).

This study suggests that the low-dose SRL+ weekly pevisoman regimen represents a new option for cost-effective optimal biochemical control
in uncontrolled limb patients requiring combination therapy.
In addition, Prof.
Maria Fleseriu made clear recommendations for increasing the dose of SRL titration and the application path of the combination regimen (Figure 2)³
.

Figure 2.
Increase the SRL titration dose and the choice path for the combination protocol

summary

In summary, determining the optimal treatment regimen at the beginning of treatment is important to improve long-term outcomes in patients with MP, where a standard-dose lenreotide ATG monotherapy regimen can be effective in managing patients
with MP in the real world 。 For patients with large limbs without biochemical control in SRL monotherapy, increasing the dose of SRL titration, selecting the appropriate EDI regimen and SRL combined with pevisoman regimen are all reference treatment options, among which the increased titration dose of lanreotide ATG, the efficacy, safety and cost-effectiveness of EDI and the combination pevisomone regimen have been verified by many times, which provides clinicians with effective, safe, personalized needs and high compliance treatment plans for patients with large limbs.
Provides important treatment ideas
.

*Octreotide LAR Chinese instructions do not approve the indication of extended dosing interval (EDI), only the interpretation of research data is used here
.

**Lanreotide ATG Chinese instructions do not approve the use and dosage of high dose (HD) (180 mg/4 weeks) and high frequency (HF) (120 mg/3 weeks), and only the research data is interpreted
here.

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References:

1.
 Thierry Brue, et al.
First-generation somatostatin receptor ligands in the treatment of acromegaly: real-world patient journey.
Presented at 2022 ENEA.
Poster P42

2.
 Maria Fleseriu, et al.
Patterns of somatostatin receptor ligand dosage and titration in patients with acromegaly: a real-world evidence study.
Presented at 2022 ENEA.
Poster P39.

3.
 Maria Fleseriu, et al.
Exploring treatment regimens in acromegaly.
Presented at 2022 ENEA.

4.
Giustina A, et al.
J Clin Endocrinol Metab.
2017 Jul 1; 102(7):2454-2464.

5.
Bonert V, et al.
J Clin Endocrinol Metab 2020; 105:dgaa444.

Approval number: SOM-CN-001426

Validity: October 19, 2023