Feola Tiziana, Carbonara Francesca, Verrico Monica, Di Crescenzo Rosa Maria, Gianno Francesca, Colonnese Claudio, Arcella Antonietta, de Alcubierre Dario, Tomao Silverio, Esposito Vincenzo, Giangaspero Felice, Minniti Giuseppe, Jaffrain-Rea Marie-Lise
Neuromed IRCCS, 86077 Pozzilli, Italy.
Department of Experimental Medicine, La Sapienza University of Rome, 00185 Rome, Italy.
Cancers (Basel). 2022 Aug 24;14(17):4093. doi: 10.3390/cancers14174093.
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.
侵袭性和转移性垂体神经内分泌肿瘤（PitNETs）是具有挑战性的病症。免疫检查点抑制剂（ICIs）目前被用于对替莫唑胺（TMZ）耐药的病例。然而，临床经验基本上仅限于病例报告，结果各不相同。材料与方法：根据肿瘤特征，对文献中12例侵袭性/转移性PitNETs接受ICIs治疗的效果进行回顾和分析，并额外描述了1例对帕博利珠单抗有反应的沉默型Pit1转移性肿瘤。结果：大多数病例为转移性（10/13：6例促肾上腺皮质激素细胞型、3例催乳素细胞型、1例沉默型Pit1）；3例为侵袭性（2例促肾上腺皮质激素细胞型、1例催乳素细胞型）。ICIs单独使用或联合使用。在最后一次对ICI的随访中，3例出现完全缓解（CR），2例出现部分缓解（PR）（转移性病例中4/5）。报告了1例疾病稳定（SD）。观察到7例疾病进展（PD），其中3例在初始SD（n = 1）或PR（n = 3）后出现，报告了2例死亡。对10例病例研究了程序性死亡配体1（PDL1）表达，2例Pit1来源的转移性PitNETs中其表达较高（>95%）（1例CR和1例显著PR），其余病例（包括1例CR和2例PR）中其表达缺失/较低（<1%）。肿瘤突变负荷升高在促肾上腺皮质激素细胞型PitNETs中可能具有参考价值，尤其是在错配修复缺陷的肿瘤中。结论：在约一半对TMZ耐药的PitNETs中记录到ICIs有显著益处。高PDL1表达与显著反应相关，但可能并非必需。基于其可接受的耐受性以及等待公认的反应预测指标，ICIs可被视为这类患者的一个有价值的选择。
