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 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.

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art / Feola, Tiziana; Carbonara, Francesca; Verrico, Monica; Maria Di Crescenzo, Rosa; Gianno, Francesca; Colonnese, Claudio; Arcella, Antonietta; DE ALCUBIERRE, Dario; Tomao, Silverio; Esposito, Vincenzo; Giangaspero, Felice; Minniti, Giuseppe; Jaffrain-Rea, Marie-Lise. - In: CANCERS. - ISSN 2072-6694. - 14:17(2022), p. 4093. [10.3390/cancers14174093]

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art

Tiziana Feola
Primo
;
Monica Verrico;Francesca Gianno;Claudio Colonnese;Antonietta Arcella;Dario de Alcubierre;Silverio Tomao;Vincenzo Esposito;Felice Giangaspero;Giuseppe Minniti
Writing – Original Draft Preparation
;
2022

Abstract

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 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.
2022
aggressive pituitary tumors; pituitary carcinoma; pituitary neuroendocrine tumors (PitNETs); temozolomide; radiotherapy; PDL1; immune checkpoint inhibitors; tumor mutational burden; mismatch repair; immune-related adverse effects; case report
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art / Feola, Tiziana; Carbonara, Francesca; Verrico, Monica; Maria Di Crescenzo, Rosa; Gianno, Francesca; Colonnese, Claudio; Arcella, Antonietta; DE ALCUBIERRE, Dario; Tomao, Silverio; Esposito, Vincenzo; Giangaspero, Felice; Minniti, Giuseppe; Jaffrain-Rea, Marie-Lise. - In: CANCERS. - ISSN 2072-6694. - 14:17(2022), p. 4093. [10.3390/cancers14174093]
File allegati a questo prodotto
File Dimensione Formato  
Feola et al_Immunotherapy for aggressive metastatic PitNETs-compresso.pdf

accesso aperto

Note: Feola_Immunotherapy_2022
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 547.18 kB
Formato Adobe PDF
547.18 kB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1652654
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 13
social impact