Tumor response and growth rate of nivolumab treatment in advanced gastric cancer: Real-world data from a large observational/translational study, JACCRO GC-08 (deliver trial).

4527 Background: Nivolumab (Nivo) demonstrated survival benefit in previously treated gastric cancer (GC) patients (pts), with a response rate (RR) of 11% and a disease control rate (DCR) of 40% (Kang YK, et al. Lancet 2017). There are few real-world data of Nivo and its predictive markers are needed in GC. It has been demonstrated that some tumors grow rapidly after Nivo treatment, but the proportion is uncertain. Methods: DELIVER trial was a prospective, multicenter, observational/translational study which assessed pts with advanced GC treated with Nivo alone and ECOG Performance Status (PS) 0-2 (UMIN000030850). The aims were to evaluate the efficacy and safety of Nivo in real world, and to discover novel host-related immune-biomarkers (gut microbiome, genetic polymorphism, gene expression, and metabolome) using fecal and blood samples which were collected before and after Nivo treatment. The RR, DCR, progression-free survival, overall survival, and tumor growth rate (TGR) were estimated as the efficacy. The response was evaluated by first imaging based on RECIST version 1.1. The TGR was calculated as a percentage increase in tumor volume during 1 month (Champiat et al. Clin Cancer Res 2017). Results: A total of 501 pts was enrolled in this study from Mar 2018 to Aug 2019, and 487 pts were evaluable for analysis (median age 70-y, 71% male, ECOG PS0/1/2 42%/44%/14%, tub/por/sig 45%/41%/5%, 21% HER2-pos, 42% pts with ascites). The DCR was 39.2% (95%CI 34.9-43.7) in evaluable pts. In 282 pts with measurable lesions, the RR was 6.7% (95%CI 4.1-10.3) and DCR was 36.5%. Sub-analysis by patient background indicated that DCR was 41% for PS0, 42% for PS1, and 24% for PS2. In addition, the DCR was lower in pts with ascites compared to those without ascites (28.6% vs. 47.0%, p= 0.005). The TGR decreased after introduction of Nivo in 124 (56.6%) of 219 evaluable pts for TGR; however, 20.5% pts were identified as experiencing hyper-progressive disease (HPD) which was defined as a ≥2-fold increase of the TGR before and after Nivo. When defining HPD as a ≥2-fold increase of tumor growth kinetics ratio and 50% increase of tumor burden, 9.6% pts experienced it. Conclusions: The real-word data of the large observational trial showed a comparable DCR to that of clinical trial in advanced GC treated with Nivo. This trial revealed the tumor behavior and some pts who experienced rapid tumor growth after Nivo treatment in clinical practice; biomarkers for HPD and the definition should be established. Clinical trial information: UMIN000030850 .

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The rate of tumor growth, g, as a biomarker for overall survival (OS) in prostate cancer (PC) in clinical trials as well as in real-world data from the Veterans Administration Medical Centers (VAMCs).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5074 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5074-5074

Author(s):

Harshraj Leuva ◽

Mengxi Zhou ◽

Julia Wilkerson ◽

Keith Sigel ◽

Ta-Chueh Hsu ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Clinical Trials ◽

Tumor Growth ◽

Real World ◽

Clinical Trial Data ◽

Trial Data ◽

Real World Data ◽

World Data

5074 Background: Novel assessments of efficacy are needed to improve determination of treatment outcomes in clinical trials and in real-world settings. Methods: Cancer treatments usually lead to concurrent regression and growth of the drug-sensitive and drug-resistant fractions of a tumor, respectively. We have exploited novel methods of analysis that assess these two simultaneous processes and have estimated rates of tumor growth ( g) and regression ( d) in over 30,000 patients (pts) with diverse tumors. Results: In prostate cancer (PC) we have analyzed both clinical trial and real-world data from Veterans. Using clinical trial data from 6819 pts enrolled in 15 treatment arms we have established separately and by combining all the data that g correlates highly (p<0.0001) with overall survival (OS) – slower g associated with better OS. In PC, abiraterone (ABI) and docetaxel (DOC) are superior to placebo, prednisone and mitoxantrone. ABI (median g =0.0017) is superior to DOC ( g=0.0021) in first line (p=0.0013); and ABI in 2nd line ( g=0.0034) is inferior to ABI in 1st line ( g=0.0017; p<0.0001). Finally, using combined clinical trial data as a benchmark we could assess the efficacy of novel therapies in as few as 30-40 patients. Amongst 7457 Veterans, the median g on a taxane ( g=0.0022) was similar to that from clinical trials ( g=0.0012). Although only 258 Veterans received cabazitaxel (CAB), g values for CAB ( g=0.0018) and DOC ( g=0.0023) were indistinguishable (p=0.3) consistent with their identical mechanism of action. Finally, outcomes with DOC in African American (AA) ( g=0.00212) and Caucasian ( g=0.00205) Veterans were indistinguishable (p=0.9) and comparable across all VAMCs. Conclusions: The rate of tumor growth, g, is an excellent biomarker for OS both in clinical trials and in real-world settings. g allows comparisons between trials and for large trial data sets to be used as benchmarks of efficacy. Real-world outcomes in the VAMCs are similar to those in clinical trials. In the egalitarian VAMCs DOC efficacy in PC is comparable in AA and Caucasian Veterans -- indicating inferior outcomes reported in AAs are likely due to differential health care access, not differences in biology.

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Survival analysis by tumor response from real-world data in advanced gastric cancer treated with nivolumab: The DELIVER trial (JACCRO GC-08).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4044 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4044-4044

Author(s):

Yosuke Kito ◽

Eisuke Inoue ◽

Yusuke Akamaru ◽

Masazumi Takahashi ◽

Jin Matsuyama ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Survival Time ◽

Advanced Gastric Cancer ◽

Real World ◽

Tumor Response ◽

Phase Iii ◽

Clinical Factors ◽

Real World Data ◽

World Data

4044 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.

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Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data

BMC Cancer ◽

10.1186/s12885-021-08058-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tae-Hwan Kim ◽

Hun Do Cho ◽

Yong Won Choi ◽

Hyun Woo Lee ◽

Seok Yun Kang ◽

...

Keyword(s):

Gastric Cancer ◽

Real World ◽

Group Performance ◽

Eastern Cooperative Oncology Group ◽

Conversion Surgery ◽

Single Center ◽

Her2 Positive ◽

Real World Data ◽

World Data ◽

The Real

Abstract Background Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. Methods This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. Results With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. Conclusions Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.

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