Confirmed clinical efficacy of nivolumab in a real-world population of advanced gastric cancer patients
The updated analysis of the DELIVER trial demonstrated that a treatment with nivolumab for patients with advanced gastric cancer in a real-world setting yields comparable clinical outcomes to what was seen in the pivotal ATTRACTION-2 trial. With nivolumab, a disease control rate of 39.2% and a response rate of 6.7% was obtained with survival times that will likely be comparable to those of the ATTRACTION-2 trial (data still immature). In addition, the DELIVER trial revealed the tumour behaviour of some patients who experienced rapid tumour growth after nivolumab treatment in clinical practice.
In the ATTRACTION-2 trial, nivolumab demonstrated a survival benefit and manageable safety profile in previously treated patients with advanced gastric cancer or gastroesophageal junction cancer. In this trial, an objective response rate (ORR) of 11.9% was reported, with a disease control rate (DCR) of 40.3%. However, there are few real-world data of nivolumab treatment for patients in clinical practice and no prospective data for patients with a performance status of 2, severe peritoneal dissemination or ascites. In addition, it has been demonstrated that some tumours grow rapidly after nivolumab treatment, but it is unclear how large this proportion of patients is. Therefore, the observational/translational DELIVER study was performed to evaluate the efficacy and safety of nivolumab for advanced gastric cancer in the real-world and to discover novel host-related immune-biomarkers, including gut microbiome.
In total, 501 patients with advanced gastric or gastroesophageal junction cancer and a performance status of 0-2 who were at least 20 years old were registered for the study. Before receiving nivolumab in any treatment line, faecal samples were collected to allow a gut microbiome analysis and blood samples were collected to perform gene expression, SNPs and metabolome analyses. At the time of disease progression or intolerance to nivolumab, a second blood and faecal sample was taken.
In total, 487 patients were included in the analysis of whom 282 had measurable lesions and 219 patients were eligible for hyper-progressive disease (HPD). The median age of study participants was 70 years and 71% of them was male. Half of the patients previously underwent a gastrectomy and almost 60% of the patients had received at least three prior chemotherapy regimens. In total, 42% had ascites and 47% suffered from peritoneal metastases.
The response rate to nivolumab among patients with measurable tumour lesions (N= 282) was 6.7% with a disease control rate of 39.2% among all patients. The tumour growth rate (TGR; i.e. the percentage increase in tumour volume during one month) in patients with evaluable data for HPD (N= 219) decreased in 56.6% of patients. However, 45 (20.5%) patients were identified as experiencing HPD, which was defined as a ≥ two-fold increase in the TGR before and after nivolumab treatment. A subgroup analysis by patient background demonstrated that the DCR was 41% for patients with an ECOG performance status (PS) of 0, 42% for patients with PS1 and only 24% for patients with PS2. In addition, the DCR was significantly lower in patients with ascites compared to those without ascites (28.6% vs. 47.0%, p= 0.005).
Compared to the ATTRACTION-2 trial, the response rate in DELIVER was slightly lower (11.2% vs. 6.7%) while the disease control rates were highly comparable (40.3% vs. 36.5%, respectively). Preliminary survival data after a median follow-up of 5.62 months indicate that both median progression-free survival and overall survival will likely be comparable to those reported in ATTRACTION-2 trial, but data are still immature. A safety analysis performed in the first 200 patients indicate that some common adverse events such as diarrhoea, fatigue, decreased appetite and nausea were observed more frequently as compared to the ATTRACTION-2 trial. This may reflect the clinical practice, including patients with poor performance status or conditions.
The real-world data of this large observational trial demonstrated comparable clinical outcomes to those of the ATTRACTION-2 clinical trial in patients with advanced gastric cancer treated with nivolumab. In addition, this trial revealed the tumour behaviour of patients who experienced rapid tumour growth after nivolumab treatment in clinical practice. Nevertheless, biomarkers for HPD and the definition thereof should still be established. Results of the microbiome biomarker study will be presented at a future meeting.
Sunakawa Y, Sakamoto Y, Inoue E, et al. Updated analysis of DELIVER trial (JACCRO GC-08): A large observational/translational study of nivolumab treatment in advanced gastric cancer. Presented at ESMO World GI 2020; Abstract LBA-4.