Background
Generic name | Trade name | Target | Application |
---|---|---|---|
pembrolizumab | Keytruda | PD-1 | melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, microsatellite instability-high cancer, gastric cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, urothelial carcinoma |
nivolumab | Opdivo | PD-1 | metastatic small cell lung cancer, metastatic melanoma, metastatic urothelial carcinoma, metastatic colorectal cancer, hepatocellular carcinoma, metastatic nonsmall cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, metastatic squamous cell carcinoma of the head and neck |
ipilimumab | Yervoy | CTLA-4 | advanced renal cell carcinoma, adult and pediatric microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, cutaneous melanoma, unresectable or metastatic melanoma |
atezolizumab | Tecentriq | PD-L1 | urothelial carcinoma, non-small cell lung cancer, triple-negative breast cancer, small cell lung cancer |
avelumab | Bavencio | PD-L1 | metastatic Merkel cell carcinoma, locally advanced or metastatic urothelial carcinoma [10] |
Predictive biomarkers of the efficacy of PD-1 blockade therapy
PD-1/PD-L1 expression
Antigen recognition initiates the immune response
Functional status of immune cells is related to anti-tumor immunity
Infiltration of immune cells in the tumor microenvironment is a prerequisite for anti-tumor immunity
Intestinal microbial flora affects host immune function
Mechanism underlying resistance to PD-1/PD-L1 blockade
T cell dysfunction-mediated resistance
Antigen recognition disorders
T cell activation disorders
Decrease in T cell infiltration
T cell depletion leads to resistance to PD-1 blockade therapy
Resistance caused by changes in PD-L1 expression
Combination therapy to improve the efficacy of PD-1/PD-L1 blockade
Combination therapeutic strategies to enhance T cell activation
Combination therapeutic strategy to enhance T immune cell function and infiltration
Combination therapeutic strategy for combined chemoradiotherapy
Immunological checkpoint inhibitor | Combined drug | Application | Number of volunteers | OS (months) | Rate of OS (at 6 months) | ORR (%) | DOR (months) | PFS (months) |
---|---|---|---|---|---|---|---|---|
pembrolizumab | Epacadostat [168] | Unresectable or metastatic melanoma | 354 | – | 84.1 | 34.2 | – | 4.70 |
Pomalidomide+Dexamethasone [169] | Refractory or relapsed and refractory multiple myeloma | 126 | 21.0 (14.2-NA) | – | – | – | 5.7 | |
nivolumab | Previously untreated advanced melanoma | 313 | – | 0.86 | 57.6 | – | 11.50 | |
Previously untreated advanced or metastatic renal cell carcinoma | 550 | – | – | 38.7 | – | 12.42 | ||
ipilimumab | Sargramostim [172] | stage III or stage IV melanoma untreatable by surgery | 123 | 17.5 (14.9-NA) | – | – | – | 3.10 |
Dacarbazine [173] | untreated unresectable stage III or IV melanoma | 250 | 11.17 | – | – | 19.3 | 2.76 | |
Paclitaxel/ Carboplatin [174] | Lung cancer—non small cell squamous | 388 | 13.37 | – | – | – | 5.55 | |
Nab-Paclitaxel + Carboplatin [175] | Non-squamous non-Small cell lung cancer | 483 | 18.6 | – | – | – | 7.00 | |
atezolizumab | Carboplatin + Etoposide [176] | Untreated extensive-stage small cell lung cancer | 201 | 12.3 | – | – | – | 5.2 |
Cobimetinib [177] | Metastatic colorectal adenocarcinoma | 183 | 8.87 | – | – | 1.97 | 1.91 | |
Bevacizumab [178] | Renal cell carcinoma | 178 | – | – | – | – | 8.90 |