Table 1.
Characteristics and main outcomes of selected randomized clinical trials in patients with ALK-translocated lung cancer.
| Name of the trial | First author and year of publication | Treatment in the control arm: drug/dose (n of pts) | Treatment in the experimental arm: drug/dose (n of pts) | Median follow-up time in the control arm | Median follow-up time in the experimental arm | Primary endpoint | PFS control vs experimental arm | PFS: HR (95% CI) and p value (experimental vs control) | OS: HR (95% CI) and p value (experimental vs control) | |
|---|---|---|---|---|---|---|---|---|---|---|
| ALEX (19) | Peters et al., 2017 | crizotinib 250 mg BID (151) |
alectinib 600 mg BID (152) |
17.6 months | 18.6 months | PFS (IA) | 1y PFS rate; 48.7% (95% CI: 40.4-56.9%) |
1y PFS rate: 68.4% (95% CI: 61-75.9%) | 0.47 (95% CI: 0.34-0.65). p<0.001 | 0.76 (95% CI: 0.48-1.2). p=0.24 |
| J-ALEX (20) | Hida et al., 2017 | crizotinib 250 mg BID (104) |
alectinib 300 mg BID (103) |
12.2 months | 12 months | PFS (IRF) | Median: 10.2 months (range: 8.2-12.0) | Median: NE (range: 20.3 months-NE) | 0.34 (95% CI: 0.17-0.71). p<0.0001 | NA |
| ALTA-1L (21) | Camidge et al., 2020 | crizotinib 250 mg BID (137) |
brigatinib 180 mg QD (with 7-day lead-in at 90 mg QD) (136) |
NA | 24.9 months | PFS (BIRC) | Median: 11.0 months (range: 9.2-12.9) | Median: 24.0 months (range: 18.5-NR) | 0.49 (95% CI: 0.35-0.68). p=0.0001 | 0.92 (95% CI: 0.57-1.47). p=0.771 |
| ASCEND-4 (8) | Soria et al., 2017 | platinum-based CT: cisplatin 75 mg/m2 or carboplatin AUC 5-6 + pemetrexed 500 mg/m2 q3w for 4 cycles followed by pemetrexed maintenance (175) |
ceritinib 750 mg QD (189) |
NA | NA | PFS (BIRC) | Median: 8.1 months (range: 5.8-11.1) | Median: 16.6 months (range: 12.6-27.2) | 0.55 (95% CI: 0.42-0.73). p<0.00001 | 0.73 (95% CI: 0.5-1.08). p=0.056 |
| ALESIA (22) | Zhou et al., 2019 | crizotinib 250 mg BID (62) |
alectinib 600 mg BID (125) |
15 months | 16.2 months | PFS (IA) | Median: 11.1 months (range: 9.1-13.0) | Median: NE (range: 9,1 months-NE) | 0.22 (95% CI: 0.13-0.38). p<0.0001 | 0.28 (95% CI: 0.12-0.68). p=0.0027 |
| eXalt3 (23) | Horn et al., 2021 | crizotinib 250 mg BID (146) |
ensartinib 225 mg QD (143) |
20.2 months | 23.8 months | PFS (BIRC) | Median: 12.7 months (range: 0.03-38.6) | Median: 25.8 months (range: 0.03-44.0) | 0.51 (95% CI: 0.35-0.72). p<0.001 | 0.91 (95% CI: 0.54-1.54). p=0.73 |
| CROWN (24) | Shaw et al., 2020 | crizotinib 250 mg BID (142) |
lorlatinib 100 mg QD (149) |
14.8 months | 18.3 months | PFS (BIRC) | 1y PFS rate; 39% (95% CI: 30-48%) |
1y PFS rate: 78% (95% CI: 70-84%) | 0.28 (95% CI: 0.19-0.41). p<0.001 | 0.72 (95% CI: 0.41-1.25). p= NA |
BID, bis in die; BIRC, blinded independent review committee; CI, confidence interval; IA, investigator assessed; IRF, assessed by independent review facility; NA, not available; NE, not estimable; NR, not reached; OS, overall survival; PFS, progression free survival; QD, quaque die.