Perioperative treatment and biomarker analysis of LP002, an anti-PD-L1 antibody, plus chemotherapy in resectable gastric and gastroesophageal junction cancer.

Autor: Tang JL; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhang B; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Xu JP; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Qi L; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Xin D; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Wang L; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Wang BZ; Department of Pathology and Resident Training Base, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Tian YT; Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Li Y; Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Huang J; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2023 Mar; Vol. 12 (5), pp. 5639-5648. Date of Electronic Publication: 2022 Nov 07.
DOI: 10.1002/cam4.5414
Abstrakt: Background: The addition of immune checkpoint inhibitors to perioperative chemotherapy in operable gastric or gastroesophageal junction (GEJ) cancer has become one of the research hotspots, while reliable biomarkers for efficacy are lacking. We conducted a phase 1 trial to assess the safety and efficacy of LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in patients with gastric or GEJ cancer.
Methods: We enrolled patients with resectable and PD-L1 positive gastric or GEJ cancers. Eligible patients received three preoperative and six postoperative cycles of intravenous LP002 with cisplatin and 5-fluorouracil, repeated every 2 weeks. The primary endpoint was safety. Secondary endpoints included rate of margin-free (R0) resection and pathological complete response (pCR). We also characterized changes in the tumor immune microenvironment using multiplex immunofluorescence (MIF) staining and next-generation sequencing (NGS) with pre- and post-treatment tumor samples.
Results: Thirty patients were enrolled, of whom 28 had GEJ cancer. With a median follow-up of 7.9 months, all patients completed preoperative treatment, and 27 patients underwent surgery. Twenty-four patients underwent R0 resection. Six patients (20.0%) had Mandard tumor regression grade (TRG) 1-3, including one achieving pCR. Twenty-seven patients had treatment-related adverse events (TRAEs), while grade 3-4 TRAEs were observed in 11 patients. No treatment-related deaths occurred. MIF staining revealed that TRG 1-3 group was associated with a higher density of PD-L1+/CD68+ cells in the pre-treatment tumor parenchyma than TRG 4-5 group (p = 0.048). NGS studies with paired pre- and post-treatment tumor samples revealed the disappearance of pre-existing mutations, the emergence of new mutations, and variations in the abundance of mutations after preoperative LP002 and chemotherapy. Meanwhile, tumor mutational burden decreased in patients with TRG 1-3 (p = 0.0313).
Conclusions: LP002 plus cisplatin and 5-fluorouracil are safe in patients with gastric or GEJ cancer, and patient selection via appropriate biomarkers is needed in the future.
(© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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