Table 1.
New therapeutic perspectives.
| Drug and Study. | Posology | Indication | CT Phase | Design | Arms | n | Primary Endpoint | Control Group | PD Cutoff | Results |
|---|---|---|---|---|---|---|---|---|---|---|
| Atezolizumab IMvigor211 |
1200 mg every 3 weeks | Second line after Pt or first line in the ineligible patients | III | Open Label | 2 | 931 | OS | Chemotherapy (vinflunine or docetaxel or paclitaxel) | ≥5% ≥1% |
At 30 months 18.1 % Atezolizumab, 9.8% control |
| (A) Atezolizumab + Cisplatin IMvigor130 | 1200 mg every 3 weeks + chemotherapy | First line | III | Medley | 3 | 1213 | OS, PFS | (B) Atezolizumab alone, (C) Placebo + platinum based chemotherapy | ≥5% ≥1% |
PFS: A = 8.2 months, C = 6.3 months OS: A = 16 months, C = 13.4 months |
| Atezolizumab IMvigor210 cohort 1 |
1200 mg every 3 weeks | First line | II | - | 1 | 119 | ORR | - | ≥5% ≥1% |
At 17.2 months of follow up ORR in the 23% of patients |
| Atezolizumab IMvigor210 cohort 2 |
1200 mg every 3 weeks until progression | Second line after Pt | II | - | 1 | 310 | ORR and immune modified RECIST | Historical control ORR = 10% | ≥5% ≥1% |
At 21.1 months ORR = 28% in PD-L1 ≥ 5% and 19.3% in PD-L1 ≥ 1% |
| Avelumab B9991001 |
At a dosage of 10 mg/kg of body weight every 2 weeks | Maintenance of Platinum-based chemotherapy | III | Open Label | 2 | 700 | OS | BSC | PD-L1 positive | At 12 months OS Avelumab = 71.3%, OS BSC = 58.4% |
| Nivolumab CA209275 |
3 mg/kg | Progressive during or after platinum therapy | II | - | 1 | 270 | ORR | Historical control ORR = 10% | ≥5% ≥1% |
At a minimum follow-up of 6 months ORR: PD-L1 ≥ 5 28%, PD-L1 ≥ 1% 23.8%, PD-L1 < 1% 16% |
| Nivolumab CA209032 |
3 mg/kg every 2 weeks until progression | Second line | I/II | - | 1 | 78 | ORR | - | ≥1% | At a minimum follow-up of 9 months ORR in 19 patients out of 78 |
| Nivolumab CA209274 |
3 mg/kg | After surgical resection | III | Double Blind | 2 | 709 | DFS | Placebo | ≥1% | 20.8 months Nivolumab, 10.8 placebo |
| Pembrolizumab KEYNOTE-045 |
200 mg every 3 weeks or chemotherapy | Second line after Pt | III | Open Label | 2 | 542 | OS, PFS | Chemotherapy (vinflunine or docetaxel or paclitaxel) | ≥10% | OS in all population 10.3 months in Pembrolizumab, 7.4 months in control arm OS in PD-L1 ≥ 10% respectively 8 e 5.2 months. |
| Pembrolizumab KEYNOTE-052 |
200 mg every 3 weeks | First line | II | - | 1 | 374 | OR | - | ≥10% | 89 (24%, 95% CI 20–29) of 370 patients had a centrally assessed OR |
| (A) Pembrolizumab + chemotherapy KEYNOTE-361 |
200 mg every 3 weeks or 200 mg every 3 weeks+chemotherapy or chemotherapy alone | First line | III | Open Label | 3 | 1010 | OS, PFS | (B) Pembrolizumab alone, (C) Chemotherapy alone | PD-L1 CPS of at least 10 | There were no statistically significant differences |
| Enfortumab + chemotherapy EV-301 |
1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle | After previous treatments with platinum-containing chemotherapy and a PD-1 inhibitor/L1 | III | Open Label | 2 | 608 | OS, PFS | Chemotherapy alone | - | OS was longer in the EV group than in the chemotherapy group (12.88 vs. 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI], 0.56 to 0.89; p = 0.001). PFS was also longer in the EV group than in the chemotherapy group (5.55 vs. 3.71 months; hazard ratio for progression or death, 0.62; 95% CI, 0.51 to 0.75; p < 0.001) |
| Enfortumab EV-201 |
1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle | After previous treatments with platinum-containing chemotherapy and a PD-1 inhibitor/L1 | II | - | 1 | 125 | ORR | - | - | ORR: 52% (95% CI 41–62) |
| Sacituzumab TROPHY-U-01 |
10 mg/kg on days 1 and 8 of 21-day cycles | After previous treatments who had progressed after prior PLT and CPI | II | Open Label | 1 | 113 | ORR, OS, PFS | - | - | DOR: 7.2 months (95% CI, 4.7 to 8.6 months); PFS: 5.4 months (95% CI, 3.5 to 7.2 months); OS: 10.9 months (95% CI, 9.0 to 13.8 months) |