Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumors

被引:6
作者
De Rycke, Ophelie [1 ,2 ]
Walter, Thomas [3 ]
Perrier, Marine [4 ]
Hentic, Olivia [1 ]
Lombard-Bohas, Catherine [3 ]
Coriat, Romain [5 ]
Cadiot, Guillaume [4 ]
Couvelard, Anne [2 ,6 ]
Ruszniewski, Philippe [1 ,2 ]
Cros, Jerome [2 ,6 ]
de Mestier, Louis [1 ,2 ]
机构
[1] Beaujon Univ Hosp, ENETS Ctr Excellence, Dept Gastroenterol & Pancreatol, Clichy, France
[2] Univ Paris, Ctr Rech Inflammat, INSERM, Paris, France
[3] Edouard Herriot Univ Hosp, Hosp Civils Lyon, Dept Gastroenterol & Oncol, Lyon, France
[4] Robert Debre Univ Hosp, Dept Hepatogastroenterol & Digest Oncol, Reims, France
[5] Cochin Univ Hosp, Dept Gastroenterol, Paris, France
[6] Bichat Beaujon Univ Hosp, ENETS Ctr Excellence, Dept Pathol, Paris, France
关键词
rechallenge; alkylating agent; temozolomide; dacarbazine; neuroendocrine tumor; pancreas; Mgmt; MGMT PROMOTER METHYLATION; NEOPLASMS NEN; TEMOZOLOMIDE; CANCER; TRIAL; CAPECITABINE; GUIDELINES; THERAPY; NETS;
D O I
10.1530/ERC-21-0034
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A rechallenge is common after the initial efficacy of alkylating-based chemotherapy (ALK) in pancreatic neuroendocrine tumors (PanNET). High MGMT expression seems associated with a lower response to ALK. We aimed to evaluate the efficacy and toxicity of ALK rechallenge in PanNET, and to assess the evolution of MGMT expression under ALK. All consecutive patients with advanced PanNETs who received initial ALK (achieving tumor control) followed by a pause of > 3 months, then an ALK rechallenge (ALK2) upon progression were retrospectively studied (cohort A). The primary endpoint was progression-free survival under ALK2 (PFS2). The MGMT expression was retrospectively assessed by immunohistochemistry (H-score) in consecutive PanNET surgically resected following ALK (cohort B). We found that Cohort A included 62 patients (median Ki67 8%), for whom ALK1 followed by a pause achieved an objective re sponse rate of 55% and a PFS1 of 23.7 months (95% IC, 19.8-27.6). ALK2 achieved no objective response and stability in 62% of patients. The median PFS2 was 9.2 months (IC 95% 7.1-11.3). At multivariable analysis, a hormonal syndrome (P = 0.032) and a pause longer than 12 months (P = 0.041) were associated with a longer PFS2. In cohort B (17 patients), the median MGMT H-score increased from 45 (IQR 18-105) before ALK to 100 (IQR 56-180) after ALK (P = 0.003). We conclude that after the initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain the low efficacy of ALK rechallenge.
引用
收藏
页码:457 / 466
页数:10
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