PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial

Juan Du, Changchang Lu, Liang Mao, Yahui Zhu, Weiwei Kong, Shanshan Shen, Min Tang, Shanhua Bao, Hao Cheng, Gang Li, Jun Chen, Qi Li, Jian He, Aimei Li, Xin Qiu, Qing Gu, Dongsheng Chen, Chuang Qi, Yunjie Song, Xiaoping Qian, Lei Wang, Yudong Qiu, Baorui Liu, Juan Du, Changchang Lu, Liang Mao, Yahui Zhu, Weiwei Kong, Shanshan Shen, Min Tang, Shanhua Bao, Hao Cheng, Gang Li, Jun Chen, Qi Li, Jian He, Aimei Li, Xin Qiu, Qing Gu, Dongsheng Chen, Chuang Qi, Yunjie Song, Xiaoping Qian, Lei Wang, Yudong Qiu, Baorui Liu

Abstract

This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC, respectively). Twenty-nine patients are enrolled in the study. The objective response rate (ORR) is 60%, and the R0 resection rate is 90% (9/10). The 12-month progression-free survival (PFS) rate and 12-month overall survival (OS) rate are 64% and 72%, respectively. Grade 3 or higher adverse events are anemia (8%), thrombocytopenia (8%), and jaundice (8%). Circulating tumor DNA analysis reveals that patients with a >50% decline in maximal somatic variant allelic frequency (maxVAF) between the first clinical evaluation and baseline have a longer survival outcome and a higher response rate and surgical rate than those who are not. PD-1 blockade plus chemoradiotherapy as preoperative therapy displays promising antitumor activity, and multiomics potential predictive biomarkers are identified and warrant further verification.

Keywords: PD-1 blockade; borderline resectable pancreatic cancer; circulating tumor DNA; locally advanced pancreatic cancer; preoperative therapy.

Conflict of interest statement

Declaration of interests D.C., Y.S., and C.Q. were employed by Jiangsu Simcere Diagnostics Co., Ltd.

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Study design (A) Flowchart of the enrolled patients. (B) Timeline of the treatment.
Figure 2
Figure 2
Treatment response and survival analysis (A) Best percentage change from baseline on the basis of radiologic response. (B) Duration of responses of patients in the ITT population. The length of each bar represents the duration of treatment of each patient. (C and D) The Kaplan-Meier curves of (C) PFS and (D) OS in all enrolled patients. (E and F) The Kaplan-Meier curves of (E) PFS and (F) OS stratified by tumor type. (G and H) The Kaplan-Meier curves of (G) PFS and (H) OS stratified by surgical margin. PR, partial response; SD, stable disease; PD, disease progression; EOT, end of treatment; OS, overall survival; PFS, progression-free survival; BRPC, borderline resectable pancreatic cancer; LAPC, locally advanced pancreatic cancer.
Figure 3
Figure 3
Association between peripheral blood biomarkers and treatment response (A and B) The Kaplan-Meier curves of (A) PFS and (B) OS of patients stratified by PBEC (declined vs. elevated). (C and D) The Kaplan-Meier curves of (C) PFS and (D) OS of patients stratified by CA19-9 change between baseline and after four treatment cycles (decline vs. elevated). (E and F) The Kaplan-Meier curves of (E) PFS and (F) OS of patients stratified by CA19-9 decline from baseline, two treatment cycles, and four treatment cycles (continuous decline vs. non-continuous decline). (G) Clinical response of patients stratified by CA19-9 decline from baseline, two treatment cycles, and four treatment cycles (continuous decline vs. non-continuous decline). (H) Surgery margin of the patients stratified by CA19-9 decline from baseline, two treatment cycles, and four treatment cycles (continuous decline vs. non-continuous decline).
Figure 4
Figure 4
ctDNA dynamics and correlation with treatment response (A and B) The Kaplan-Meier curves of (A) PFS and (B) OS of patients stratified by change of ctDNA (T1-T2 mVAF decline vs. non-decline). (C) Treatment response of patients stratified by change of ctDNA (T1-T2 mVAF decline vs. non-decline). (D and E) The Kaplan-Meier curves of (D) PFS and (E) OS of patients stratified by decline of ctDNA (T1-T2 mVAF > 50% vs.  50% vs.  50% vs. 

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