Table 1.
Selected trials for monotherapy checkpoint inhibitor and VEGF TKI in unresectable gastroesophageal cancer
| Trial | Interventions | Phases | Treatment setting | Results |
|---|---|---|---|---|
| NCT00548548 | Bevacizumab + CTx versus CTx | III | 1st line |
ORR: 46 versus 37% PFS: 6.7 versus 5.3 mo OS: 12.1 versus 10.1 mo Most common grade 3–4 AE: neutropenia (35%), anemia (10%), anorexia (8%) |
|
REGARD RAINBOW |
Ramucirumab versus BSC Ramucirumab + CTx versus CTx |
III | 2nd line |
OS: Ramucirumab versus BSC: 5.2 versus 3.8 mo Ramucirumab + CTx versus CTx: 9.6 versus 7.4 mo Grade 3–4 AEs: 57% versus 58% (REGARD) Grade 3–4 AEs: 47% versus 42% (RAINBOW) |
| INTEGRATE | Regorafenib versus placebo | II | 2 or fewer lines of Tx |
PFS: 2.6 versus 0.9 mo Grade 3–4 AE: 67% versus 52% |
| NCT00940225 | Cabozantinib | II | Advanced, recurrent, or metastatic |
ORR: 10% DCR: 33% Grade 3–4 AE: 74.5% |
| KEYNOTE-59 | Pembrolizumab | II |
3rd line PD-L1 + |
ORR: 15.5% mDOR: 16.3 mo Grade 3–5 AE: 17.8% |
| KEYNOTE-62 | Pembrolizumab or Pembrolizumab + CTx versus CTx | III | 1st line |
mOS: 10.6 versus 11.1 mo (CPS 1 or higher) PFS: 6.9 versus 6.4 mo (CPS 1 or higher) Grade 3–4 AE: 17% versus 73% versus 69% (Pembro versus Pembro + CTx versus CTx) |
| KEYNOTE-180 | Pembrolizumab | II | 3rd line |
Overall ORR: 9.9% mDOR: NR (1.9–14.4 mo) Grade 3–4 AE: 12.4% |
| KEYNOTE-61 | Pembrolizumab versus Paclitaxel | III | 2nd line |
mOS: 9.1 versus 8.3 mo mPFS: 1.5 versus 4.1 mo Grade 3–5 AE: 14% versus 35% |
| KEYNOTE-181 | Pembrolizumab versus CTx | III | 2nd line |
mOS: 9.3 versus 6.7 mo (CPS 10 or higher) Grade 3–5 AE: 18.2% versus 40.9% |
| KEYNOTE-590 | Pembrolizumab + CTx versus CTx | III | 1st line |
mOS: 12.4 versus 9.8 mo mDOR: 8.3 versus 6.0 mo Discontinuation rates due to AEs: 19% versus 12% |
| CheckMate-649 | Nivolumab + CTx versus CTx | III | 1st line |
mOS: 13.8 versus 11.6 mo (overall) mOS: 14.0 versus 11.3 mo (CPS 1 or higher) mOS: 14.4 versus 11.1 mo (CPS 5 or higher) Grade 3–4 AEs: 59% versus 44% |
| CheckMate-32 | Nivolumab w/wo ipilimumab | I/II | 2nd line |
ORR 12%, 24% 12-mo OS: 39%, 35% Grade 3–4 AEs: 17% versus 47% versus 27%* |
| ATTRACTION-2 | Nivolumab versus placebo | III | 2nd line |
mOS: 5.3 versus 4.1 mo 12-mo OS: 26.2 versus 10.9% Grade 3–4 AEs: 10% versus 4% |
| JAVELIN Gastric 300 | Avelumab versus CTx | III | 3rd line |
mOS: 4.6 versus 5.0 mo PFS: 1.4 versus 2.7 mo ORR: 2.2 versus 4.3% Grade 3–4 AEs: 9.2% versus 31.6% |
| NCT02340975 | Durvalumab w/wo ipilimumab | I/II | 2nd line |
ORR: 0%, 7.4% 12 mo OS: 4.6%, 37% Grade 3–4 AEs: 17% versus 4%, versus 42% versus 16%** |
*Nivolumab only versus Nivolumab 1 mg/kg + ipilimumab 3 mg/kg versus nivolumab 3 mg/kg + ipilimumab 1 mg/kg
**Durvalumab + tremelimumab in 2nd line setting versus durvalumab only versus trememlimumab only versus durvalumab + tremelimumab in 3rd line setting