Table 2.
Main prospective clinical trials with crizotinib.
| Clinical Trial | Phase | N of Patients | Median Age (Range) |
ROS1 Testing Techinique |
Previous Lines | ORR% (95% CI) |
mPFS Months (95% CI) |
mOS Months (95% CI) |
CNS Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| PROFILE 1001 [57] | 1 | 53 | 53 (25–77) |
51 FISH 2 RT-PCR |
≥0 | 72 (58–83) | 19.3 (15.2–39.1) |
51.4 (29.3–NR) |
- |
| OxOnc [65] | 2 | 127 | 51.5 (22.8–79.7) |
RT-PCR | ≤3 | 71.7 (63.0–79.3) |
15.9 (12.9–24) |
32.5 (32.5–NR) |
mPFS 10.2 (95% CI 5.6–13.1) vs. 18.8 months (13.1–NR) a |
| EUCROSS [64] | 2 | 34 b | 56 (33–84) | FISH c | 16 ≤ 1 14 ≥ 2 |
70 (51–85) |
20.0 (10.1–NR) |
NR (17.1–NR) |
mPFS 9.4 (1.7–NR) vs. 20.0 months (10.1–NR) HR 1.53; 95% CI 0.488–4.7; p = 0.464) a |
| AcSè [62] | 2 | 37 d | 62 (33–81) | FISH | median 2 (range 1–7) |
69.4 (53–82) e |
5.5 (4.2–9.1) |
17.2 (6.8–32.8) |
- |
| METROS [63] | 2 | 26 | 68 (28–86) | FISH | ≥1 | 65 (44–82) |
22.8 (15.2–30.3) |
NR | ORR 33% (2/6) |
ORR: Objective Response Rate; mPFS: median Progression Free Survival; mOS: median Overall Survival; CNS: Central Nervous System; FISH: Fluorescense in situ Hybridization; RT-PCR: Reverse-transcriptase-polymerase-chain-reaction; NR: Not Reached; HR: Hazard Ratio. a Patients with baseline brain metastases versus patients without brain metastases; b 4 patients were excluded from efficacy analysis; c DNA Sequencing on 20 samples, with confirmed rearrangements on 18 samples; d 36 evaluable; e best overall response rate; ORR assessed at two cycles 47.2% (95% CI 30.4–64.5).