Table 1.
Selected clinical studies of ALK inhibitors for advanced ALK-positive NSCLC.
| Drug | Study name or ClinicalTrials.gov identifier | Phase | Population | Comparator | n | ORR | PFS | Adverse effects or remarks |
|---|---|---|---|---|---|---|---|---|
| Crizotinib | PROFILE 1007 Shaw et al. [2013] | III | Platinum-based chemotherapy pretreated | Pemetrexed or docetaxel | 347 | 65% versus. 20% (p < .001) | 7.7 versus 3.0 months (HR: 0.49, 95% CI 0.37–0.64; p < .001) | Visual disorder (60%), diarrhoea (60%), nausea (55%), vomiting (47%), constipation (42%), elevated aminotransferase levels (38%), oedema (31%), fatigue (27%) |
| PROFILE 1014 Solomon et al. [2014] | III | Treatment naïve, nonsquamous NSCLC | Platinum plus pemetrexed | 343 | 74% versus. 45% (p < .001) | 10.9 versus 7.0 months (HR 0.45, 95% CI 0.35–0.60; p < .001) | Visual disorder (71%), diarrhoea (61%), oedema (49%), vomiting (46%), constipation (43%), elevated aminotransferase levels (36%), upper respiratory infection (32%), abdominal pain (26%) | |
| Ceritinib | ASCEND-1 Shaw et al. [2014] | I | Advanced malignancy* | No | 114 | 58% (95% CI 0.48–0.67) | 7.0 months (95% CI 5.6–9.5) | Nausea (82%), diarrhoea (75%), vomiting (65%), fatigue (47%), and increased ALT level (35%) |
| NCT01685060 | II | Chemotherapy and crizotinib pretreated | No | NA | NA | NA | Ongoing clinical trial | |
| NCT01685138 | II | Crizotinib-naïve | No | NA | NA | NA | Ongoing clinical trial | |
| ASCEND-4 | III | Treatment naïve, nonsquamous NSCLC | Platinum plus pemetrexed | NA | NA | NA | Ongoing clinical trial | |
| ASCEND-5 | III | Platinum-based chemotherapy and crizotinib pretreated | Pemetrexed or docetaxel | NA | NA | NA | Ongoing clinical trial | |
| Alectinib$ | AF-001JP‡ Seto et al. [2013] | I/II | ALK-inhibitor-naïve | No | 46 | 93.5%, (95% CI 82.1–98.6) | NA | Dysgeusia (30%), increased AST level (28%), increased blood bilirubin level (28%), increased blood creatinine level (26%), rash (26%), constipation (24%), stomatitis (15%), and myalgia (13%). |
| AF-002JGGadgeel et al. [2014] | I/II | Crizotinib pretreated | No | 47 | 55% | NA | Fatigue (30%), myalgia (17%), and peripheral oedema (15%) | |
| NCT01871805 | II | Chemotherapy and crizotinib pretreated | No | NA | NA | NA | Ongoing clinical trial | |
| ALEX | III | Treatment naïve | Crizotinib | NA | NA | NA | Ongoing clinical trial | |
| AP26113 | NCT01449461 Gettinger et al. [2014b] | I/II | Crizotinib pretreated or ALK inhibitor naïve | No | 57 | Crizotinib pretreated: 69% (95% CI 54–81%) | Crizotinib pretreated: 10.9 months | Nausea (34%), diarrhoea (26%), fatigue (22%), and vomiting (16%) |
| ALTA | II | Crizotinib pretreated | No | NA | NA | NA | Ongoing clinical trial |
*
Advanced malignancies were not restricted to NSCLC.
$
This drug was approved only in Japan as of September 2014.
‡
This study was conducted in Japan with Japan Pharmaceutical Information Center, number JapicCTI-101264.
ALK, anaplastic lymphoma kinase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; HR, hazard ratio; NA, not available; ORR, overall response rate; PFS, progression-free survival.