Abstract 1558P
Background
The Keystone-001 study was designed to prospectively evaluate the efficacy and safety of preoperative treatment with pembrolizumab plus paclitaxel and cisplatin followed by Da Vinci robotic radical surgery in patients with locally advanced (stage III) ESCC. The study also explored the potential mechanism of this treatment strategy (NCT 04389177, 5/15/2020).
Methods
The full study methods for this prospective, single-arm, single-center, open-label, phase-II study have been published previously. For further investigating the immune cell subpopulations that determine the efficacy, we performed single-cell sequencing on peripheral blood and tumor tissues after neoadjuvant therapy, and validated using flow cytometry.
Results
Of the 49 patients enrolled between July 8, 2020, and February 10, 2022, 47 received neoadjuvant therapy and were included in the ITT analysis. Among all patients who received neoadjuvant therapy, no grade ≥3 AEs were reported. Improvements from baseline nutritional status were observed with increases in patients’ median body weight and NRI. QoL evaluations showed improvements from baseline to post-adjuvant therapy in all functional scales and symptom scales of EORTC QLQ-C30 and in all items of the EORTC QLQ-OES18 questionnaire. Among all 45 patients in the efficacy analysis, the MPR rate was 73.3%, the pCR rate was 42.2%, the ORR was 95.6%, and the DCR was 100%. After a median follow-up of 23.3 months (95% CI 20.6, 24.9; maximum follow-up 34 months), the 1- and 2-year OS and DFS rates were 95.6 and 90.5% and 95.6 and 86.3%, respectively. The single-cell sequencing results showed that the main cell populations that affect the response of this treatment strategy were NKT and NK cell subpopulations in peripheral blood. Further analysis results showed that the TRGC2+NKT and FGFBP2+NK cell subpopulation in peripheral blood were more significantly increased in peripheral blood from patients with a good response.
Conclusions
The preliminary findings of this trial were safe and effective, and further phase III studies (Keystone-002) have begun to recruit participants.
Clinical trial identification
NCT 04389177.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Tianjin Science and Technology Bureau, Beijing Xisike Clinical Oncology Foundation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1521P - Addition of durvalumab to CROSS in oesophageal adenocarcinoma is feasible and safe
Presenter: Hans Schloesser
Session: Poster session 21
1523P - Phase II dose optimization results from MOUNTAINEER-02: A study of tucatinib, trastuzumab, ramucirumab, and paclitaxel for HER2+ gastroesophageal cancer (GEC)
Presenter: Mustapha Tehfe
Session: Poster session 21
1524P - First-line TST001 plus capecitabine and oxaliplatin (CAPOX) for advanced G/GEJ cancer with CLDN18.2 positive overall survival data from study transtar102-Cohort C
Presenter: Lin Shen
Session: Poster session 21
1526P - Phase Ib results of bemarituzumab (BEMA)+mfolfox6+nivolumab (NIVO) for advanced gastric/gastroesophageal junction cancer (G/GEJC): Fortitude-102 part 1
Presenter: Zev Wainberg
Session: Poster session 21
1527P - Efficacy and safety of infigratinib in locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients with FGFR2 gene amplification
Presenter: Jiajia Yuan
Session: Poster session 21
1528P - A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
Presenter: Daniel Olson
Session: Poster session 21
1529P - Tislelizumab plus chemotherapy sequential neo-chemoradiotherapy therapy as total neoadjuvant therapy in locally advanced esophageal squamous cell carcinoma (ETNT)
Presenter: Wenwu He
Session: Poster session 21
1530P - Health-related quality of life (hrqol) in patients with claudin-18 isoform 2-positive (CLDN18.2+) locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma: Results from SPOTLIGHT and GLOW
Presenter: Florian Lordick
Session: Poster session 21