Page 68 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Chapter 3
Chapter 3
66
62
Study /References
Target
Drug
Phase
Tumor Type
Number of enrolled patients
Clinical End Point
(NCT02340975) (MEDI4736) [1, 2]
CTLA-4
Tremelimumab
2
GC 2nd line
18
A partial response was observed in one patient while steady progression was observed in four patients. The adverse effect such as CEA.TR-TEAEs: ≥ 3 TR- TEAE, Fatigue, thrombocytopenia, and anemia were also observed. Autoimmune hepatitis and hepatic failure were observed in one treatment-related death patient. 8.87 months (IQR 6.57-12.37) was the follow-up median for surviving patients in the nivolumab group, 5.26 months with (95% CI 4.60-6.37) is the overall survival median in the nivolumab group. The overall survival rate of 26.2% was observed within the nivolumab group compare to 10.9% within the placebo group. There are grade 4 treatment-related adverse effect in 10% of the 330 patients from the nivolumab
NCT02267343[3]
CTLA-4
Ipilimumab
3
Gastric or Gastroesophage al Junction Cancer cohort
330
(NCT01848834) (NCT02370498) (NCT01848834) (NCT02335411) [4-11]
PD-1
Pembrolizumab
1b
PDL1+ GC Cohort
39
Central review: ORR 22% median response period of 40-weeks. Overall response rate: 11.4 months. Progression-free survival: 1.9 months.PD-L1 association and overall response rate by central and investigator review was 22% (95% CI 10-39) and 33% (95% CI 19-50) respectively. Eight weeks (range 7-16) was recorded as the median period of response. An overall survival of 69% over the period of 6-month was recorded with a PD-L1 expression level progressive survival rate (PFS) of 24% over a period of 6-month was associated with ORR (1-sided P = 0.10).
(NCT01772004 ) (MSB0010718C) [2,12]
PDL-1
Avelumab
1b
Japanese GC All comers 2 cohorts
75
( 20-second line
and 55- maintenance)
Central review: ORR. 15 % and 7.3 % progression-free survival over the period of 11.6 weeks and 14.1 weeks respectively. Progression-free survival was observed in 7 patients out of the 20-second line patients, and 43 out of the 55 maintenance patients with evaluation of PD-L1 expression level. In the second line group of 20 patients, a Progression-free survival median of 36.0 wks (95% CI: 6.0, 36.0) was observed for PD-L1+ expression level and 11.6 wks (2.1, 21.9) for PD-L1 expression level. Furthermore,inthemaintenancegroupof55patients,aProgression-freesurvival median of 17.6 wks (5.9, 18.0) was observed for PD-L1+ expression level and 11.6 wks (5.7, 17.7), for PD-L1 expression level.
(NCT01693562 ) (MEDI4736) [13, 14]
PDL-1
Durvalumab
1
Gastric Cancer cohort with none specified PD-L1 positive status
16 of 346
Central review: ORR of 25 % PD-L1 association and response.
MPDL3280A (MPDL3280A) [15-17]
PDL-1
Atezolizumab
1
GC cohort All comers
1 of 171
Partial response in one patient was observed with a PD-L1 association and PFS of 42% within 24 weeks. PD-L1 expression level status was evaluated in 94 patients who had a tumor. The PD-L2 EXPRESSION LEVEL evaluation was done in 81 patients with an expression twice higher than PD-L1 expression from positive tumor patients compared to the negative PD-L1 tumor patients. Thirteen out of the 33 patients had an ORR of 39% with positive PD-L1 expression level compare to the 13% (8/61) of patients who expressed negative PD-L1 in neg tumors.
Table 1: Main features of included clinical trials with immune checkpoint therapies in gastric cancer
Advanced
ORR; overall response rate, MOS; median overall survival, PFS; median progression-free survival, w; week, m; month