Signifor LAR (pasireotide long acting release)

Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.

Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).

Pasireotide-LAR allowed the normalization of insulin-like growth factor 1 (IGF1) values in all patients and reduced tumour residue volume where present. A good safety profile and long-term tolerability were also reported.

Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 μg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks...Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.

Tumor shrinkage was observed in 6 out of 7 evaluated responders, with no cases of size increase during the long-term follow-up. Pas-LAR is effective and safe and the early identification of responders is possible just after the first administration.

In real-life settings, PAS-LAR significantly decreases symptoms, IGF-1 levels, and the size of adenoma in patients with acromegaly resistant to SRLs. Beneficial effects may occur early after the first injection.

Depending on the route of administration in the parent study, pts received pasireotide long-acting release (LAR; n=303) or subcutaneous (sc; n=38) as monotherapy (n=36), or sc in combination with cabergoline (n=2). Hyperglycemia is an expected AE during pasireotide treatment, often occurring in the first 3 months of therapy. These data in pts with acromegaly, CD or other endocrine disorders support pasireotide as a well-tolerated long-term treatment and affirm that pts continue to receive long-term benefit, with a low discontinuation rate over 8 years.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins.

Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control.

Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.

This study aimed to assess whether clinical, biochemical, imaging and pathological characteristics can predict surgical remission and response to first-generation somatostatin receptor ligands (SRLs) and pasireotide-LAR in acromegaly...Fasting GH concentration <36.6 µg/L and DG tumor turned out to be independent predictors of good response to first-generation SRLs (OR=0.96, p=0.06 and OR=10.68, p=0.002, respectively). Younger age at diagnosis, male sex, lower GH, IGF-1 and PRL concentrations, smaller tumor size at diagnosis as well as positive α-SU staining, lower Ki-67 index and DG tumors predicted better treatment outcome in acromegaly patients.

The combination of everolimus and pasireotide-LAR showed promising efficacy over single agent. The delayed combination of everolimus and pasireotide-LAR following progression on single agent everolimus appeared intriguing as a combination strategy.

Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.

Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

Conclusion The immunohistochemical analysis of SSTR subtypes expression in pituitary adenoma patients especially with acromegaly and complicated clinical course might be helpful for decision making or prognostic significance. Our case reports point to the need of clinical trials for further investigation.

We propose SOM230 as an anti-metastatic therapy in PDA for its capacity to remodel the fibrotic and immunosuppressive myeloid stroma. This pharmacotherapy should benefit PDA patients treated with chemotherapies.

In agreement, inhibition of mutated RET in TT cells reduced SST2 expression. In conclusion, we demonstrated that octreotide and pasireotide inhibited cell proliferation and invasiveness in a subset of MTC, supporting their potential use in the control of tumor growth.

TAF-derived cytokines may increase PitNETs aggressiveness, alter angiogenesis and induce epithelial-to-mesenchymal transition changes. Pasireotide's inhibitory effect on TAF-derived cytokines suggest that this effect may play a role in its anti-tumour effects.