Survival analysis by tumor response from real-world data in advanced gastric cancer treated with nivolumab: The DELIVER trial (JACCRO GC-08).
Authors: Kito Yosuke , Inoue Eisuke , Akamaru Yusuke , Takahashi Masazumi , Matsuyama Jin , Yabusaki Hiroshi , Makiyama Akitaka , Suzuki Takahisa , Tsuda Masahiro , Yasui Hisateru , Hirabayashi Naoki , Takeno Atsushi , Kawakami Hisato , Okuda Hiroyuki , Yoshioka Takashi , Kawada Junji , Kodera Yasuhiro , Ichikawa Wataru , Fujii Masashi , Sunakawa Yu 
Published: June 2021

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Background: The phase III ATTRACTION-2 trial demonstrated survival benefit of nivolumab (Nivo) as third- or later-line treatment in previously treated advanced gastric or gastroesophageal junction (GEJ) cancer, with response rate (RR) of 11% (Kang YK, et al. Lancet 2017). It has been shown that some tumors grow rapidly after Nivo treatment, but the proportion and survival are still uncertain. We therefore prospectively investigated clinical outcomes from real-world data of Nivo treatment in advanced gastric cancer (GC). Methods: The DELIVER trial was a prospective, multicenter, observational study which assessed patients (pts) with advanced gastric or GEJ adenocarcinoma treated with Nivo alone and ECOG PS 0-2 (UMIN000030850). The aims were to evaluate the efficacy and safety of Nivo treatment in real world. Primary endpoint was overall survival (OS), secondary endpoints were RR, disease control rate (DCR), progression-free survival (PFS), tumor growth rate (TGR) at 1st evaluation, and safety. The sub-group analyses were performed for survival according to tumor response and clinical factors. The survival data was fixed at the timepoint of 1 year after the last enrollment. Results: In 501 pts enrolled from Mar 2018 to Aug 2019, 487 pts were evaluable (median age 70y, 71% male, ECOG PS0/1/2 42/44/14%, no. of prior regimen 1/2/≥3 2/39/59%, 21% HER2-pos, 42% pts with ascites). Median OS was 5.8 months (m) (95%CI 5.3-7.0) with 1y-survival rate of 30%, and median PFS was 1.8 m (95%CI 1.7-2.0), at 454 events for PFS and 389 events for OS. The DCR were 39.4%, and RR was 14.2% in 282 pts with measurable lesions. Median OS and PFS by tumor response (CR/PR/SD/PD) were Not Reached (NR)/NR/11.3/4.1m and NR/11.7/3.8/1.4m, respectively. A sub-group analysis of OS by clinical factors is the following: male/female; 6.5/5.0m ( p= 0.002), tub/por/sig; 8.1/5.4/4.1m ( p< 0.0001), albumin < 3.5/≥3.5; 4.2/8.9m ( p< 0.0001), w/peritoneal mets/w/o; 4.9/8.4m ( p< 0.0001), and w/ascites/w/o; 3.7/8.9m ( p< 0.0001). These findings were also observed in PFS. In 219 evaluable pts for TGR, 20.5% pts were identified as hyper-progressive disease (HPD). An exploratory approach by logistic regression analysis indicated that level of free-T3 in blood before Nivo treatment was higher in the HPD compared to the non-HPD group (2.5 vs. 2.2 pg/ml, p= 0.005). Survival time was comparable between the HPD group and PD without HPD group. Median period from 1st evaluation to death was 2.8 m for HPD, 5.7 m for non-HPD, and 2.4 m for PD at 1st evaluation without HPD. Conclusions: The real-world data of Nivo treatment in advanced GC indicated comparable survival to previous result in a clinical trial. Differences in survival time by tumor response or some clinical factors were observed in Nivo treatment. In addition, our study revealed the rate of HPD and the prognosis in advanced GC pts treated with Nivo. Clinical trial information: UMIN000030850.