Table 2.
Results of most relevant clinical trials on immune checkpoint inhibitors for gastrointestinal cancers.
| Tumor type | Treatment | Phase | ClinicalTrials.gov identifier | Patient feature | Clinical outcome | Reference |
|---|---|---|---|---|---|---|
| Esophageal cancer | Pembrolizumab versus Paclitaxel, Docetaxel, or Irinotecan | III | KEYNOTE-181 (NCT02564263) |
628 patients with advanced EC that progressed after 1 line of
therapy 222 patients with PD-L1 CPS ⩾10 401 patients with ESCC |
[PD-L1 CPS ⩾10] mOS: 9.3 versus 6.7 months (HR = 0.69 [95% CI: 0.52–0.93]; p = 0.0074) [ESCC] mOS: 8.2 versus 7.1 m (HR = 0.78 [95% CI: 0.63–0.96]; p = 0.0095) |
Shah et al.36 |
| Nivolumab versus
Paclitaxel or Docetaxel |
III | ATTRACTION-3 (NCT02569242) |
Patients with EC who have been refractory or intolerant to one
previous fluoropyrimidine-based and platinum-based
chemotherapy Nivolumab: 210 patients Paclitaxel or Docetaxel: 209 patients |
mOS: 10.9 versus 8.4 month (HR = 0.77 [95% CI: 0.62–0.96; p = 0.019]) |
Kato et al.37 | |
| Gastric and Gastroesophageal junction cancer | Nivolumab versus placebo | III | ATTRACTION-2 (NCT02267343) |
493 patients with advanced GC/GEJc who had been treated with ⩾2 chemotherapy regimens | ORR: 11.2% versus 0% DCR: 40.3% versus 25% mPFS: 1.61 versus 1.45 month (HR = 0.60 [95% CI: 0.49–0.75]; p < 0.0001) mOS: 5.26 versus 4.14 month (HR = 0.63 [95% CI: 0.51–0.78]; p < 0.0001) |
Kang et al.38 |
| Nivolumab + SOX or Nivolumab + CapeOX | II/III | ATTRACTION-4 (NCT02746796) |
<phase II> Patients with previously untreated, unresectable, advanced, or recurrent HER2-negative GC/GEJc Nivolumab + SOX (NS): 21 patients Nivolumab + CapeOX (NC): 18 patients |
ORR: 57.1% (NS) 76.5% (NC) mPFS: 9.7 months (NS) 10.6 months (NC) |
Boku et al.39 | |
| Pembrolizumab | II | KEYNOTE-059 (NCT02335411) |
259 patients with advanced GC/GEJc with ⩾2 prior lines of treatment | ORR: 11.6% (6 CRs) DCR: 28% mDOR: 8.4 months mPFS: 2.0 months mOS: 5.6 months |
Fuchs et al.40 | |
| Pembrolizumab versus Paclitaxel | III | KEYNOTE-061 (NCT02370498) |
592 patients (395 PD-L1 CPS ⩾1) with advanced GC/GEJc that
progressed on first-line chemotherapy with a platinum and
fluoropyrimidine Pembrolizumab arm: 207 GC/89 GEJc (196 PD-L1 CPS ⩾1) Paclitaxel arm: 200 GC/96 GEJc (199 PD-L1 CPS ⩾1) |
Pembrolizumab versus Paclitaxel (PD-L1 CPS
⩾1) ORR: 16% versus 14% mDOR: 18.0 versus 5.2 month mPFS: 1.5 versus 4.1 month (HR = 1.27 [95% CI: 1.03–1.57]) mOS: 9.1 versus 8.3 month (HR = 0.82 [95% CI: 0.66–1.03]) |
Shitara et al.41 | |
| Pembrolizumab or Pembrolizumab + chemotherapy or placebo + chemotherapy | III | KEYNOTE-062 (NCT02494583) |
Randomized study of first-line pembrolizumab or
pembrolizumab + chemotherapy versus
placebo + chemotherapy in 763 patients with PD-L1 CPS ⩾1,
HER2-negative, advanced GC/GEJc (69% GC/30% GEJc) (281 patients [37%] PD-L1 CPS ⩾10) |
Pembrolizumab versus chemotherapy mOS: 10.6 versus 11.1 month (HR = 0.91 [95% CI: 0.69–1.18]) [PD-L1 CPS ⩾10 ]mOS: 17.4 versus 10.8 month (HR = 0.69 [95% CI: 0.49–0.97]) |
Tabernero et al.42 | |
| Colorectal cancer | Pembrolizumab | II | KEYNOTE-164 (NCT02460198) |
63 patients with MSI-H/dMMR mCRC with ⩾1 prior line of therapy | ORR: 58% (2 CRs and 18 PRs) |
Le et al.43 |
| Pembrolizumab | III | KEYNOTE-177 (NCT02563002) | 307 patients with MSI-H/dMMR mCRC were randomly assigned 1:1 to
first-line pembrolizumab or investigator’s choice of mFOLFOX6 or
FOLFIRI ± bevacizumab or cetuximab
(chemotherapy) Pembrolizumab: 153 patients Chemotherapy: 154 patients |
Pembrolizumab versus chemotherapy mPFS: 16.5 versus 8.2 month (HR = 0.60 [95% CI: 0.45–0.80]; p = 0.0002) 12-month PFS: 55.3% versus 37.3% 24-month PFS: 48.3% versus 18.6% ORR: 43.8% versus 33.1% |
Thierry et al. 44 | |
| Nivolumab + low-dose Ipilimumab | II | CheckMate-142 (NCT02060188) |
Preciously treated 119 patients with MSI-H/dMMR mCRC | ORR: 58% DCR: 81% |
Overman et al.45 | |
| Atezolizumab + cobimetinib (MEK1/2 inhibitor) and atezolizumab
monotherapy versus regorafenib |
III | IMblaze370 (NCT02788279) |
Previously treated 363 patients with unresectable mCRC were
randomized to 2:1:1 Atezolizumab + cobimetinib (A+C): 183 patients Atezolizumab monotherapy (A): 90 patients Regorafenib (R): 90 patients |
mOS: 8.9 months (A+C) 7.1 months (A) 8.5 months (R) |
Bendell et al.46 | |
| Hepatocellular carcinoma | Nivolumab | I/II | CheckMate-040 (NCT01658878) |
262 patients with advanced HCC | ORR: 18.2% | Crocenzi et al.47 |
| Nivolumab | III | CheckMate-459 (NCT02576509) |
Nivolumab versus sorafenib as a first-line treatment in 1009 patients with unresectable HCC | HR = 0.85 [95% CI: 0.72–1.02]; p = 0.0752 | Press Release on June 2448 | |
| Pembrolizumab | II | KEYNOTE-224 (NCT02702414) |
104 patients with HCC who had previously treated with sorafenib | ORR: 17% (1 CR and 17 PRs) |
Zhu et al.49 | |
| Pembrolizumab | III | KEYNOTE-240 (NCT02702401) |
Pembrolizumab versus BSC as a second-line
therapy (413 patients) (278 in pembrolizumab and 135 in placebo) |
Pembrolizumab improved OS (HR = 0.78) and PFS
(HR = 0.78) (Not reached the prespecified statistical criteria) ORR: 16.9% versus 2.2% |
Finn et al.50 | |
| Pembrolizumab +Lenvatinib | Ib | KEYNOTE-524 (NCT03006926) |
First-line treatment for advanced unresectable HCC | ORR: 46% (95% CI: 36.0–56.3) mOS: 22.0 months mPFS: 9.3 months (11 CRs and 35 PRs) |
ASCO2020 Virtual Scientific Program51 | |
| Nivolumab + pilimumab | I/II | CheckMate-040 (NCT01658878) |
148 patients with advanced HCC who were previously treated with
sorafenib (arm A) nivolumab/ipilimumab every 3 weeks (arm B) nivolumab/ipilimumab every 2 weeks (arm C) nivolumab/ipilimumab every 6 weeks |
In arm A, the mOS was 23 months and 4 of the 50 patients had a CR | Thomas et al.52 | |
| Atezolizumab + Bevacizumab |
III | IMbrave150 (NCT03434379) |
Randomized study of first-line atezolizumab + bevacizumab
versus sorafenib in 501 patients with
unresectable HCC Atezolizumab + bevacizumab: 336 patients Sorafenib: 165 patients |
Atezolizumab + bevacizumab significantly improved OS (HR = 0.58) and PFS (HR = 0.59) compared with sorafenib | Finn et al.53 | |
| Biliary tract cancers | Pembrolizumab | II | KEYNOTE-158 (NCT02628067) |
104 patients with advanced BTC and prior progression/intolerance on standard therapy | ORR: 6.6% (PD-L1 positive) 2.9% (PD-L1 negative) |
Ueno et al.33 |
| Nivolumab monotherapy or in combination with cisplatin + gemcitabine | I | JapicCTI-153098 | 60 patients with unresectable or recurrent BTC (30 in nivolumab monotherapy and 30 in nivolumab + cisplatin-gemcitabine) |
Nivolumab monotherpy versus
combination mOS: 5.2 versus 15.4 months mPFS: 1.4 versus 4.2 months ORR: 1/30 versus 11/30 |
Ueno et al.54 | |
| Durvalumab with or without tremelimumab | I | NCT01938612 | 107 patients with advanced BTC (42 in durvalumab monotherapy [D] and 65 in durvalumab + tremelimumab [D+T]) |
DCR at 12 weeks: 16.7% (D) 32.2% (D+T) |
Ioka et al.55 | |
| Pancreatic cancer | Ipilimumab | II | - | 27 patients with locally advanced or metastatic pancreas adenocarcinoma | ORR: 0% 1 delayed response |
Royal et al.56 |
| Durvalumab with or without tremelimumab | II | NCT02558894 | 65 patients with advanced pancreatic cancer (33 in durvalumab monotherapy [D] and 32 in durvalumab + tremelimumab [D+T]) |
ORR: 0% (D), 3.1% (D+T) DCR: 6.1% (D), 9.4% (D+T) |
O’Reilly et al. 57 |
BSC, best supportive care; BTC, biliary tract cancer; CapeOX, capecitabine plus oxaliplatin; CI, confidence interval; CPS, combined positive score; CR, complete response; DCR, disease control rate; dMMR, mismatch repair deficient; EC, esophageal cancer; ESCC, esophageal squamous cell carcinoma; FOLFIRI, leucovorin plus 5-fluorouracil plus irinotecan; GC, gastric cancer; GEJc, gastroesophageal junction cancer; HCC, hepatocellular carcinoma; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; mCRC, metastatic colorectal cancer; mDOR, median duration of response; mFOLFOX6, modified oxaliplatin plus leucovorin plus 5-fluorouracil; mOS, median overall survival; mPFS, median progression-free survival; MSI-H, microsatellite instability-high; ORR, objective response rate; PD-L1, programmed cell death ligand 1; PR, partial response; SOX, S-1 plus oxaliplatin.