7856 In Pursuit of Solutions: Exploring Novel Therapeutic Strategies in the Treatment of a Rare, Aggressive Macroprolactinoma Post-Temozolomide: A Case Report
Authors: Latif Wafa A , Konindala Navya , Darapu Hima , Ruddiman Kathleen 
Published: October 2024

Abstract
Disclosure: N. Konindala: None. H. Darapu: None. K. Ruddiman: None.
Introduction: Prolactinomas comprise 40-60% of all pituitary tumors. Most prolactinomas respond well to dopamine agonist treatment. About 10% of these tumors are aggressive prolactinomas (APRL). Although rare, APRLs pose a significant challenge in clinical practice as treatment beyond dopamine agonists, surgery and radiotherapy is limited. A fourth-line therapy called temozolomide may be needed. After temozolomide failure, treatment options are minimal, as there are no evidence-based therapies available for such aggressive pituitary tumors. The efficacy of novel treatment agents remains to be explored. Notably, our case is one of the few where investigational agents, including Pembrolizumab and Pazopanib have been used. We present a case report that contributes to the evolving understanding of potential therapeutic options and highlights the ongoing challenges in refractory prolactinoma management. Case Presentation: A 77-year-old male was diagnosed with a macroprolactinoma in 2001 and was started on cabergoline with a good therapeutic response. In 2011, there was hormonal and imaging evidence of progression, and the patient underwent transsphenoidal hypophysectomy with gross resection followed by gamma knife radiation. The patient was found to have a recurrence of his tumor five years later and underwent repeat transsphenoidal resection. He continued to show evidence of recurrence and was recommended for chemoradiation and adjunct temozolomide (TMZ). After 12 cycles of TMZ, a repeat MRI was done, which showed radiographic recurrence. The patient had a third transsphenoidal surgery done in August 2022, followed by the initiation of a PARP-1 inhibitor, Olaparib. The development of adverse effects complicated this, and treatment was transitioned to capecitabine and TMZ in Jan 2023. The patient had persistent tumor burden symptoms, and a VEGF inhibitor Avastin was initiated. His symptoms initially improved, but unfortunately, his prolactin levels rose from 895 mg/dL to 1,547mg/dL, indicating evidence of disease progression. Immunotherapy with pembrolizumab was started on 6/2023, and he was given three doses before a follow-up MRI showed continued progression of the disease. He was recommended to start pazopanib, a kinase inhibitor. Discussion: Aggressive Prolactinomas present a rare and intricate management challenge, necessitating a multidisciplinary approach. Despite standard therapies, achieving remission can be elusive. While Pembrolizumab showed promise in reported cases, our patient remained refractory. Literature indicates favorable responses to Pazopanib in a small number of refractory cases. A reassessment in a few months will evaluate our patient's response to Pazopanib. This case emphasizes the need for further research to refine refractory prolactinoma management and develop response indicators for investigational agents.
Presentation: 6/3/2024