Efficacy and predictive factors of response to immunotherapy in pituitary carcinomas and aggressive pituitary tumors: a French cohort study

MD. Ilie*^a (Dr), C. Villa^b (Dr), T. Cuny^c (Dr), G. Assie^d (Prof), B. Baussart^e (Dr), M. Cancel^f (Dr), P. Chanson^g (Prof), C. Cortet^h (Dr), B. Decoudierⁱ (Dr), E. Deluche^j (Dr), AL. Di Stefano^k (Dr), D. Drui^l (Dr), S. Gaillard^e (Dr), B. Goichot^m (Prof), O. Huillardⁿ (Dr), A. Joncour^o (Dr), D. Larrieu-Ciron^p (Dr), R. Libe^d (Dr), G. Nars^m (Mr), A. Vasiljevic^q (Dr), G. Raverot^r (Prof)

^a Cancer Research Center of Lyon, Inserm U1052, CNRS UMR5286, Claude Bernard Lyon 1 University, Lyon, FRANCE ; ^b Neuropathology Department, Pitié-Salpêtrière University Hospital, AP-HP, Sorbonne University, Paris, FRANCE ; ^c Endocrinology Department, Conception University Hospital, AP-HM, Marseille, FRANCE ; ^d Endocrinology Department, Cochin University Hospital, AP-HP, Paris, FRANCE ; ^e Neurosurgery Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris, FRANCE ; ^f Oncology Department, Tours University Hospital, Tours, FRANCE ; ^g Department of Endocrinology and Reproduction Disorders, Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, FRANCE ; ^h Endocrinology Department, Lille University Hospital, Lille, FRANCE ; ⁱ Endocrinology Department, Reims University Hospital, Reims, FRANCE ; ^j Oncology Department, Limoges University Hospital, Limoges, FRANCE ; ^k Neurology Department, Foch Hospital, Suresnes, FRANCE ; ^l Endocrinology Department, Nantes University Hospital, Nantes, FRANCE ; ^m Department of Internal Medicine and Endocrinology, Strasbourg University Hospital, Strasbourg, FRANCE ; ⁿ Oncology Department, Cochin University Hospital, AP-HP, Paris, FRANCE ; ^o Oncology Department, Poitiers University Hospital, Poitiers, FRANCE ; ^p Oncology Department, IUCT-Oncopole, Toulouse, FRANCE ; ^q Pathology Department, “Groupement Hospitalier Est” Hospices Civils de Lyon, Bron, FRANCE ; ^r Endocrinology Department, “Groupement Hospitalier Est” Hospices Civils de Lyon, Bron, FRANCE

* mireladiana.ilie@gmail.com

Introduction: Immune-checkpoint inhibitors (ICIs) have raised hope for the treatment of pituitary carcinomas and aggressive pituitary tumors with the publication of the first successful case in 2018. So far, only 11 cases have been published, with variable response. Predictive factors of response to ICIs in pituitary carcinomas and aggressive pituitary tumors are lacking.

Material and methods: Multicentric, retrospective, observational cohort study of pituitary carcinomas and aggressive pituitary tumors treated with ICIs in France between 2019 and 2022.

Results: The study included six pituitary carcinomas (four corticotroph and two lactotroph) and nine aggressive pituitary tumors (five corticotroph and four lactotroph). Three corticotroph tumors (33.3%) showed partial tumor response that was maintained for at least 3 months and 10 months, respectively. One corticotroph tumor (11.1%) showed stable disease, maintained for at least 15 months. The other five corticotroph tumors (55.6%) progressed. One lactotroph tumor (16.7%) showed partial tumor response that was maintained for at least 18 months. One lactotroph tumor (16.7%) showed stable disease, maintained for 10 months. The other four lactotroph tumors (66.7%) progressed. Out of the four cases that showed partial tumor response, two demonstrated complete metabolic response, accompanied by complete biochemical response, while the other two showed a dissociated radiological response between the different lesions. Interestingly, all four cases that showed partial tumor response were carcinomas (no aggressive pituitary tumor showed partial response). Programmed death-ligand 1 (PD-L1) immunohistochemistry and CD8+ T cell infiltration were also investigated.

Discussion: Carcinomas are more responsive to ICIs than aggressive pituitary tumors. Corticotroph tumors appear to respond slightly better to ICIs compared to lactotroph tumors. In the case of a dissociated response, continuation of immunotherapy combined with local treatment appears to be a good option.

The author has declared no conflict of interest.