Table 1. Study characteristics of included randomized controlled trials.
| Author, yr, page (study name; NCT no.) (companion publications) | Population | Groups (no. randomized) | Duration of treatment, median (IQR), months | Cross-over between treatment groups allowed? | Reported outcomes of interest to this review | Funding source |
|---|---|---|---|---|---|---|
| Chemotherapy-controlled | ||||||
| Wu 2018, p. 1549 (PROFILE 1029; NCT01639001)[28, 30] | 18–70 years, ALK-positive NSCLC, with ECOG score of 0–2, with no prior systemic treatment | Crizotinib 250 mg BID (104) Chemotherapy (103) |
NR | Not reported | TR death; OS; PFS (independent review)*; | Pharma |
| Shaw 2013, p. 2385 (PROFILE 1007; NCT00932893)[16, 31] (Blackhall 2014[32]) | ≥ 18 yr, ALK-positive NSCLC, with ECOG score of 0–2, with progressive disease after one prior platinum-based chemotherapy regimen | Crizotinib, 250 mg BID (173) Chemotherapy (174) |
NR | Not during study period; participants from the chemotherapy arm could enroll in NCT00932451 | TR death; OS; PFS (independent radiologic review*) | Pharma |
| Solomon 2014, p. 2167[25] (PROFILE 1014; NCT01154140) (Thorne-Nuzzo 2017,[33] Solomon 2016[34], Solomon 2018[35]) | ≥ 18 yr, ALK-positive NSCLC, with ECOG score of 0–2, with no prior systemic treatment | Crizotinib 250 mg BID (172) Chemotherapy (171) |
10.9 (range 0.4 to 34.3) 4.1 (range 0.7 to 6.2) |
Yes; participants in the chemotherapy arm with disease progression could cross to the crizotinib arm provided safety criteria were met | TR death; OS; PFS (independent review)* | Pharma |
| Zhao 2015, p. 616[18] | ≥ 18 yr, ALK-positive NSCLC, Karnofsky performance status (KPS) score ≥ 70, following first- or second-line chemotherapy | Crizotinib, 250 mg BID (14) Chemotherapy (14) |
NR | Not reported | TR death; SAEs | Non-pharma |
| Novello 2018, p. 1409 (ALUR; NCT02604342) [26] | ALK-positive NSCLC, with ECOG score of 0–2; two prior lines of systemic therapy including one line of chemotherapy and one of crizotinib | Alectinib 600 mg BID (72) Chemotherapy (35) |
20.1 wk (range 0.4–62.1) 6.0 wk (range 1.9–47.1) |
Yes; cross-over from chemotherapy to alectinib was permitted following progression | OS; PFS (investigator-assessed)* | Pharma |
| Soria 2017, p. 917[24, 36] (ASCEND-4; NCT01828099) | ≥ 18 yr, ALK-positive NSCLC, ECOG score of 0–2, previously untreated | Ceritinib 750 mg QD (189) Chemotherapy (187) |
66.4 (30.8 to 83.7) 29.9 (13.0 to 62.3) |
Yes, participants in the chemotherapy arm could crossover to ceritinib after disease progression | TR death; OS; PFS (independent review)*; SAEs | Pharma |
| Shaw 2017, p. 874 (ASCEND-5, NCT01828112)[23, 37] (Kiura 2018[38]) | ≥ 18 yr, ALK-positive NSCLC, with WHO performance status of 0–2, one or two previous chemotherapy regimens and previous crizotinib for at least 21 d | Ceritinib 750 mg QD (115) Chemotherapy (116) |
30.3 (13.3 to 54.1) 6.3 (6.0 to 15.1) |
Yes, participants in the chemotherapy arm could cross over to the ceritinib group after disease progression | TR death; OS; PFS (independent review)* | Pharma |
| Head-to-head comparisons of ALK inhibitors | ||||||
| Zhou 2019, p. 437 (ALESIA; NCT02838420)[29] | ≥ 18 yr, ALK-positive NSCLC, ECOG score of 0–2, life expectancy of >12wk, no prior systemic therapy | Crizotinib 250 mg BID (62) Alectinib 600 mg BID (125) |
12.6 14.7 |
No | TR death; OS; PFS (investigator assessed)*; SAEs | Pharma |
| Camidge 2018, p. 1 (ALTA-1L; NCT02737501)[25] | ≥ 18 yr, ALK-positive locally advanced or metastatic NSCLC, with at least one measurable lesion, and no prior ALK-targeted therapy | Crizotinib 250 mg BID (138) Brigatinib 180 mg QD (137) |
7.4 (range 0.1 to 19.2) 9.2 (range 0.1 to 18.4) |
Yes: patients in the crizotinib group could cross over to brigatinib after disease progression | TR death; OS; PFS (independent review)* | Pharma |
| Peters 2017, p. 829 (ALEX; NCT02075840)[5, 39] (Camidge 2019[40]; Gadgeel 2018[41]) | ≥ 18 yr, ALK-positive NSCLC, with ECOG score of 0–2, with no prior systemic treatment | Crizotinib 250 mg BID (151) Alectinib 600 mg BID (152) |
17.6 (0.3 to 27.0) 18.6 (0.5 to 29.0) |
No | TR death; OS; PFS (investigator assessed)* | Phama |
| Hida 2017, p. 29[21] (J-ALEX; JAPICcti-132316) | ≥ 20 yr, ALK-positive NSCLC, with ECOG score of 0–2, ALK-inhibitor naive, chemotherapy-naïve or had received 1 regimen of chemotherapy | Crizotinib 250 mg BID (104) Alectinib 300 mg BID (103) |
NR | Not during study period; Treatment crossover after study withdrawal was allowed in both groups | TR death; PFS (independent review)* | Pharma |
| Hida 2016, p. 1642 (JP28927; JapicCTI-132186)[19] (Nishio 2018[42]) | ≥ 20 yr, ALK-positive NSCLC, with ECOG score of 0–1; prior treatment, including other ALK inhibitors, was allowed | Cross-over (300 mg BID total for all groups; 35 participants): Alectinib 20/40 mg capsules Alectinib 150 mg capsules Extension: Alectanib 300 mg BID (150 mg capsules) |
13.1 (range 11.1 to 15.0) | Yes by design during cross-over phase | TR death | Pharma |
| Kim 2017 (ALTA, NCT02094573)[22, 43] (Kawata 2019[44]) | ≥ 18 yr, ALK-positive NSCLC, with ECOG performance status of 0–2, disease progression while receiving crizotinib | Brigatinib 90 mg QD (109) Brigatinib 180 mg QD (110) |
NR | Yes, participants in the 90 mg/d group could cross to the 180 mg/d group after disease progression | PFS (independent review), SAEs | Pharma |
BID = twice daily, ECOG = Eastern Cooperative Oncology Group, NSCLC = non-small cell lung cancer, OS = overall survival, PFS = progression-free survival, QD = once daily, RCT = randomized controlled trial, SAE = serious adverse event, TR = treatment-related, WHO = World Health Organization.
*Primary outcome.