Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art.
Tiziana FeolaFrancesca CarbonaraMonica VerricoRosa Maria Di CrescenzoFrancesca GiannoClaudio ColonneseAntonietta ArcellaDario de AlcubierreSilverio TomaoVincenzo EspositoFelice GiangasperoGiuseppe MinnitiMarie-Lise Jaffrain-ReaPublished in: Cancers (2022)
Background : Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes. Material and &nbsp; Methods : The effects of ICIs on 12 aggressive/metastatic PitNETs from the literature were reviewed and analyzed according to tumor characteristics, with the additional description of a silent-Pit1 metastatic tumor responding to pembrolizumab. Results : Most cases were metastatic (10/13: 6 corticotroph, 3 lactotroph, 1 silent Pit1); 3 were aggressive (2 corticotroph, 1 lactotroph). ICIS was used either as monotherapy or in combination. At last follow-up on ICI, a complete response (CR) was present in 3 cases and a partial response (PR) in 2 cases (4/5 metastatic). One sustained stable disease (SD) was reported. Progressive disease (PD) was observed in 7 cases, 3 of them after initial SD ( n = 1) or PR ( n = 3), with 2 reported deaths. PDL1 expression was studied in 10 cases and was high (>95%) in 2 Pit1-derived metastatic PitNETs (1 CR and 1 remarkable PR) but absent/low (<1%) in the remaining cases (including 1 CP and 2 PR). Elevated tumor mutation burden could be informative in corticotroph PitNETs, especially in mismatch repair-deficient tumors. Conclusion : Significant benefits from ICIs were documented in about half of TMZ-resistant PitNETS. High PDL1 expression was associated with remarkable responses but may be dispensable. Based on their acceptable tolerance and awaiting recognized predictors of response, ICIs may be considered a valuable option for such patients.
Keyphrases
- squamous cell carcinoma
- small cell lung cancer
- newly diagnosed
- systematic review
- end stage renal disease
- multiple sclerosis
- neuroendocrine tumors
- randomized controlled trial
- prognostic factors
- chronic kidney disease
- skeletal muscle
- metabolic syndrome
- binding protein
- long non coding rna
- study protocol
- open label
- peritoneal dialysis
- weight loss
- combination therapy
- epidermal growth factor receptor