Table 1.
Efficacy of immune check-point inhibitors in EGFR-mutant NSCLC.
| Study | Subgroup | Treatment | Outcome |
|---|---|---|---|
| 1L immune strategy | |||
| 1L ICI monotherapy | |||
| KEYNOTE-010 phase I | EGFR+, TKI-naive (n = 4) EGFR+, TKI-pretreated (n = 26) |
Pembrolizumab Pembrolizumab |
ORR: 50%; mPFS: 157.5d; mOS: 559d; ORR: 4%; mPFS: 56d; mOS:120d |
| KEYNOTE-010 phase II | EGFR+, PD-L1+, TKI-naive (n = 10) | Pembrolizumab |
ORR: 0 |
| CheckMate 012 | EGFR+ (n = 7) EGFR– (n = 30) |
Nivolumab Nivolumab |
ORR: 14%; DCR: 29%; 24-wk PFS rate: 14%; mPFS: 1.8mo; mOS: 18.8mo; 18-mo OS: NC; ORR: 30%; DCR: 50%; 24-wk PFS rate: 51%; mPFS: 6.6mo; mOS: NR; 18-mo OS: 67% |
| 1L ICI+chemotherapy | |||
| CheckMate 012 | EGFR+ (n = 6) EGFR– (n = 30) |
Nivolumab+chemotherapy Nivolumab+chemotherapy |
ORR: 17%; DCR: 83%; mPFS: 4.8mo; 24-wk PFS rate: 40%; mOS: 20.5mo; 2-yr OS: 17%; ORR: 47%; DCR: 87%; mPFS: 7.5mo; 24-wk PFS rate: 60%; mOS: 24.5mo; 2-yr OS: 52% |
| 1L ICI+TKI | |||
| NCT02088112 | EGFR+, TKI-naive (n = 30) EGFR+, gefitinib-pretreated (n = 10) |
Durvalumab+gefitinib Durvalumab+gefitinib |
ORR: 63.3%; DoR:9.2mo; mPFS: 10.1mo; ORR: 70.0%; DoR:12.6mo; mPFS: 12.0mo |
| 1L ICI+ICI | |||
| CheckMate 012 | EGFR+ (n = 8) EGFR– (n = 54) |
Nivolumab+ipilimumab Nivolumab+ipilimumab |
ORR: 50%; ORR: 41% |
| 2+L immune strategy | |||
| 2+L ICI monotherapy | |||
| CheckMate 057 | EGFR+ (n = 82) EGFR– (n = 340) EGFR not report (n = 160) |
Nivolumab versus docetaxel Nivolumab versus docetaxel Nivolumab versus docetaxel |
HR 1.18 (favours docetaxel) HR 0.66 (favours nivolumab) HR 0.74 (favours nivolumab) |
| OAK | EGFR+ (n = 85) EGFR– (n = 628) |
Atezolizumab versus docetaxel Atezolizumab versus docetaxel |
HR 1.24 (favours docetaxel) HR 0.69 (favours atezolizumab) |
| KEYNOTE-010 | EGFR+, PD-L1 ⩾1% (n = 86) EGFR–, PD-L1 ⩾1% (n = 875) |
Pembrolizumab versus docetaxel Pembrolizumab versus docetaxel |
HR 0.88 (favours pembrolizumab) HR 0.66 (favours pembrolizumab) |
| ATLANTIC | EGFR+/ALK+, PD-L1 ⩾25% (n = 86) EGFR–/ALK–, PD-L1 ⩾25% (n = 875) |
Durvalumab Durvalumab |
ORR: 12%; TTR: 1.8mo; DOR: 7.4mo; mPFS: 1.9mo; mOS: 13.3mo; 1-yr OS: 54.8%; ORR: 16%; TTR: 1.9mo; DOR: 12.3mo; mPFS: 3.3mo; mOS: 10.9mo; 1-yr OS: 47.7% |
| 2+L ICI+chemotherapy | |||
| KEYNOTE-789 | EGFR+ EGFR+ |
Pembrolizumab+chemotherapy Placebo+chemotherapy |
Ongoing |
| CheckMate 722 | EGFR+ EGFR+ |
Nivolumab+chemotherapy Placebo+chemotherapy |
Ongoing |
| NCT03513666 | EGFR+, EGFR-TKI pretreated (n = 40) | Toripalimab+chemotherapy | ORR: 54.8%; DCR: 93.5%; mPFS: 7.6mo |
| 2+L ICI+ICI | |||
| KEYNOTE-021 cohorts D and H |
EGFR+, TKI-pretreated (n = 10) | Pembrolizumab+ ipilimumab | ORR: 10% |
| 2+L ICI+TKI | |||
| CheckMate 012 | EGFR+ (n = 21, 20 erlotinib-pretreated+1 TKI-naïve) | nivolumab+erlotinib | ORR: 19%; 24-wk PFS rate: 51% |
| TATTON | EGFR+, EGFR-TKI pretreated (n = 23) EGFR+, EGFR-TKI naive (n = 11) |
Osimertinib+durvalumab | ORR: 43% (9/21); incidence of interstitial lung disease:26% (6/23); ORR: 70% (7/10); incidence of interstitial lung disease:64% (7/11) |
| 2+L ICI+anti-angiogenetic agent+chemotherapy | |||
| IMpower150 | EGFR+, EGFR-TKI pretreated (n = 45) EGFR+, EGFR-TKI pretreated (n = 34) EGFR+, EGFR-TKI pretreated (n = 45) |
Atezolizumabb+Carboplatinc+Paclitaxeld Atezolizumabb+Carboplatinc+Paclitaxeld +Bevacizumab Carboplatinc+Paclitaxeld+Bevacizumab |
ORR: 36%; DOR: 5.6mo; mPFS: 6.9mo; mOS: 21.4mo; ORR: 71%; DOR: 11.1mo; mPFS: 10.2mo; mOS: NE; ORR: 42%; DOR: 4.7mo; mPFS: 6.9mo; mOS: 18.7mo |
ALK, anaplastic lymphoma kinase; d, day; DCR, disease control rate; DoR, duration of response; EGFR, epidermal growth factor receptor; HR, hazard ratio; ICI, immune checkpoint inhibitor; mo, month; mOS, median overall survival; mPFS, median progression-free survival; NC, not calculated; NE, not estimable; NR, not reached; ORR, overall response rate; PD-L1, programmed cell death ligand-1; TKI, tyrosine kinase inhibitor; TTR, time to response; wk, week; yr, year.