Table V.
Pivotal clinical efficacy of ALK-TKIs for the treatment of NSCLC.
| Study (n), (Ref.) | TKI treatment | Control | Targeted patients | Median PFS (months) [HR; 95% CIs]a | ORR%a | Median OS (HR; 95% CIs]a |
|---|---|---|---|---|---|---|
| PROFILE 1007 (n=347), (34) | Crizotinib | Docetaxel or Pemetrexed ALK-positive lung cancer with one prior platinum-based regimen | Locally advanced or metastatic | 7.7 vs. 3.0 [0.49; 0.37 to 0.64] | 65% vs. 20% | 20.3 vs. 22.8 [1.02; 0.68 to 1.54] |
| PROFILE 1014 (n=343), (35) | Crizotinib | Pemetrexed plus a platinum or carboplatin | Advanced ALK-positive non-squamous NSCLC patients without previous systemic treatment | 10.9 vs. 7.0 [0.45; 0.35 to 0.60] | 74% vs. 45% | NR vs. 47.5 [0.76; 0.548 to1.053] |
| PROFILE 1029 (n=207), (61) | Crizotinib | Docetaxel or Pemetrexed | Previously untreated ALK-positive advanced NSCLC | 11 vs. 6.8 [0.402; 0.286 to 0.565] | 87.5% vs. 45.6% | NA |
| ASCEND-4 (n=376), (43) | Ceritinib | Platinum-based chemotherapy | ALK-rearranged non-squamous NSCLC | 16.6 vs. 8.1 [0.55; 0.42 to 0.73] | NA | NR vs. 26.2 [0.73; 0.50 to 1.08] |
| ASCEND-5 (n=231), (44) | Ceritinib | Docetaxel or Pemetrexed | ALK-rearranged NSCLC patients with previous chemotherapy and crizotinib | 5.4 vs. 1.6 [0.49; 0.36 to 0.67] | 39.1% vs. 6.9% | NA |
| ALUR (n=107), (47) | Alectinib | Docetaxel or Pemetrexed | Advanced/metastatic ALK-positive NSCLC | 7.1 vs. 1.6 [0.32; 0.17 to 0.59] | 36.1% vs. 11.4% | 12.6 vs. NR [0.89; 0.35 to 2.24] |
| J-ALEX (n=207), (48) | Alectinib | Crizotinib | ALK-positive non-small cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen | NR vs. 10.2 [0.34; 0.17 to 0.71] | – | NR |
| ALEX (n=303), (49) | Alectinib | Crizotinib | Previously untreated, advanced ALK-positive NSCLC | NR vs. 11.1 [0.47; 0.34 to 0.65] | NA | NA [0.76; 0.48 to 1.20] |
| ALTA-1L (n=275), (53) | Brigatinib | Crizotinib | Advanced ALK-positive NSCLC | NR vs. 9.8 [0.49; 0.33 to 0.74] | 71% vs. 60% | NA |
ALK-TKIs, anaplastic lymphoma kinase tyrosine kinase inhibitors; PFS, progression-free survival; HR, hazard ratio; Cis, confidence intervals; NSCLC, non-small cell lung cancer; NA, not available; ORR, overall response rate; OS, overall survival; NR, not reached; NA, not available.