Phase I/II study of nab-paclitaxel combined with S-1 as adjuvant chemotherapy in diffuse type of stage III gastric or gastroesophageal junction adenocarcinoma.

person Yuehong Cui Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China info_outline Yuehong Cui, Jia Wei, Yiyi Yu, Bei Xu, Jing Wu, Xiaojing Xu, Tianshu Liu

Authors person Yuehong Cui Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China info_outline Yuehong Cui, Jia Wei, Yiyi Yu, Bei Xu, Jing Wu, Xiaojing Xu, Tianshu Liu Organizations Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China, Department of Oncology, Cancer center, Zhongshan Hospital, Fudan University, Shanghai, China Abstract Disclosures Research Funding No funding received None. Background: Diffuse type (Lauren's classification) of gastric adenocarcinoma (GAC) or gastroesophageal junction adenocarcinoma (GEJ) has a poorer prognosis than intestinal type of GAC or GEJ. Studies have shown that nab-paclitaxel combined with S-1 has a synergistic anti-tumor effect on advanced gastric cancer. We designed this trial to evaluate the efficacy and safety of nab-paclitaxel plus S-1 as adjuvant chemotherapy in diffuse type of stage III GAC or GEJ. Methods: This study was a multi-center, open-label, phase I/II study. The results of the phase I dose escalation study have already been reported, and the recommended phase II dose (RP2D) of nab-paclitaxel is 260mg/m 2 . Patients with stage III diffuse type GAC or GEJ after D2 dissection and achieved R0 resection were included in this study. S-1 monotherapy was used as adjuvant therapy in the first cycle. If absence of grade3/4 treatment-related adverse events (AEs) of S-1 monotherapy, nab-paclitaxel (260mg/m 2 , d1, q3w) and S-1 [body surface area (BSA) <1.25 m 2 , 80mg/d; BSA 1.25–1.5 m 2 , 100mg/d; BSA >1.5 m 2 , 120mg/d; d1-14, q3w] were administered for 6 cycles. Then patients still received S-1 monotherapy for 8 cycles. In phase II study, the primary endpoint was 1-year disease free survival (DFS) rate, and the secondary endpoints were 3-year DFS rate and safety. Results: From January 2021 to February 2023, a total of 42 patients were enrolled in this analysis (3 patients in nab-paclitaxel 260mg/m 2 dose group in phase I and 39 patients in phase II). The median age (range) was 53 (29~69) years, 18 patients (42.86%) were stage IIIA, 10 patients (23.81%) were stage IIIB and 14 patients (33.33%) were stage IIIC. The median follow-up time was 13.26 months. As of January 2023, 12 patients experienced recurrence. The 1-year-DFS rate was 74.07%, median DFS and 3-year-DFS rate were not reached. The incidence of adverse effects (AEs) was 78.57% (33/42), and the rate of grade 3-4 AEs was 42.86% (18/42). The most common AEs were neutropenia and leukopenia. In addition, we performed next generation sequencing (NGS) for 5 relapsed patients, and 5 non-relapsed patients who were matched to the relapsed patients. The results showed that the mutant rates of tumor supressor gene CDH1, ARID1A, KMT2D, and TP53 in non-relapsed patients were higher than that in relapsed patients. The positive rate of ctDNA were 60% in relapsed patients, but no ctDNA was detected in non-relapsed patients. Conclusions: Adjuvant chemotherapy with nab-paclitaxel and S-1 followed by S-1 monotherapy exhibited promising clinical efficacy, with acceptable tolerability. This study deserves further investigation and follow up for diffuse type of GAC or GEJ. Clinical trial information: NCT03977220.

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