Efficacy profile of pembrolizumab for primary pulmonary NUT carcinoma: A systematic review and meta-analysis.

Abstract

8586 Background: Primary pulmonary NUT carcinoma is an exceedingly rare and aggressive malignancy characterized by chromosomal rearrangements involving the NUT gene. With limited therapeutic options and an extremely poor prognosis, treatment strategies have focused on identifying effective targeted and immunotherapeutic approaches. Pembrolizumab, an anti-PD-1 immune checkpoint inhibitor, has shown promise in various malignancies, particularly those with high tumor mutational burden or PD-L1 expression. However, despite its use, its efficacy in NUT carcinoma remains poorly understood due to the rarity of this disease and a paucity of robust clinical data. This systematic review and meta-analysis aim to explore the available evidence on the clinical data of pembrolizumab in treating primary pulmonary NUT carcinoma, focusing on progression-free survival (PFS), and overall survival (OS) by consolidating outcomes from case reports and case series. Methods: A systematic review and meta-analysis were conducted to evaluate the effectiveness of pembrolizumab in the treatment of primary pulmonary NUT carcinoma. A comprehensive search of PubMed, Embase, and Cochrane was performed for articles published between January 2014 and December 2024, using the keywords “pembrolizumab,” “Pulmonary NUT carcinoma,” and “NUT midline carcinoma.” Inclusion criteria included reports of patients treated with either pembrolizumab monotherapy or pembrolizumab in conjunction with other therapies for Primary Pulmonary NUT Carcinoma for any duration. Reports that did not mention PFS or OS were excluded. Results: A total of 39 reports involving 56 patients with primary pulmonary NUT carcinoma treated with pembrolizumab, either in conjunction with other therapies or monotherapy, were analyzed. The median overall survival (OS) was 7.3 months (95% CI: 5.2–8.8), and the median progression-free survival (PFS) was 4.6 months (95% CI: 3.1–5.7). Among three patients receiving pembrolizumab monotherapy as a second-line or later treatment, the median PFS was 2.9 months. Conclusions: Pembrolizumab has been explored as second-line or later therapy for primary pulmonary NUT carcinoma based on its success in treating NSCLC. Our analysis revealed a median progression-free survival of 4.6 months and a median overall survival of 7.3 months for patients with primary pulmonary NUT carcinoma receiving pembrolizumab, illustrating the continuing challenge of treating this rare malignancy. Importantly, there are no randomized controlled trials investigating pembrolizumab in this rare malignancy, highlighting a critical gap in evidence. Prospective clinical trials and further research into biomarkers predictive of treatment response are urgently needed to optimize therapeutic strategies and improve outcomes for patients with this aggressive disease.