Table 1.
Investigator-Assessed Response Rates, PFS, and Overall Survival in the Phase 1/2 Study
| Efficacy Parameter | Patients With ALK+ NSCLC |
Patients With ALK+ NSCLC With Previous Crizotinib |
||||
|---|---|---|---|---|---|---|
| All Doses (n = 79) | 90 mg→180 mg Once Dailya (n = 28) | 180 mg Once Dailyb (n = 25) | All Doses (n = 71) | 90 mg→180 mg Once Dailya (n = 25) | 180 mg Once Dailyb (n = 23) | |
| Response characteristics | ||||||
| Confirmed ORR, n (%) | 53 (67) | 22 (79) | 17 (68) | 45 (63) | 19 (76) | 15 (65) |
| [95% CI] | [56–77] | [59–92] | [47–85] | [51–75] | [55–91] | [43–84] |
| Confirmed CR, n (%) | 8 (10) | 4 (14) | 2 (8) | 5 (7) | 3 (12) | 2 (9) |
| Confirmed PR, n (%) | 45 (57) | 18 (64) | 15 (60) | 40 (56) | 16 (64) | 13 (57) |
| DCR, n (%) | 70 (89) | 25 (89) | 20 (80) | 62 (87) | 22 (88) | 18 (78) |
| [95% CI] | [80–95] | [72–98] | [59–93] | [77–94] | [69–98] | [56–93] |
| Time to response, median (range), mo | (n = 53) 1.9 (1.2–29.4) |
(n = 22) 1.9 (1.2–6.0) |
(n = 17) 1.9 (1.6–29.4) |
(n = 45) 1.8 (1.2–29.4) |
(n = 19) 1.8 (1.2–6.0) |
(n = 15) 1.9 (1.6–29.4) |
| Duration of response, median (95% CI),c mo | 14.9 (9.9–29.5) | 14.8 (7.9–33.3) | 20.4 (7.6–44.5) | 14.5 (9.0–22.1) | 14.8 (7.9–25.1) | 20.4 (7.5–51.6) |
| PFS | ||||||
| No. of patients with events (%) | 61 (77) | 19 (68) | 21 (84) | 55 (77) | 17 (68) | 19 (83) |
| Median (95% CI),c mo | 14.5 (10.8–21.2) | 16.3 (9.2–27.5) | 14.5 (5.4–34.2) | 13.4 (9.2–16.7) | 14.7 (9.2–27.1) | 14.5 (5.4–34.1) |
| PFS probability,c % (95% CI) | ||||||
| 1 y | 57 (45–68) | 65 (43–80) | 54 (32–71) | 55 (42–66) | 65 (42–81) | 54 (32–72) |
| 2 y | 36 (25–47) | 36 (17–56) | 40 (21–59) | 31 (20–43) | 33 (14–54) | 40 (19–59) |
| 3 y | 21 (12–32) | 18 (5–38) | 27 (11–46) | 19 (10–29) | 13 (2–34) | 30 (12–49) |
| 4 y | 16 (8–26) | 18 (5–38) | 18 (6–36) | 12 (5–23) | 13 (2–34) | 20 (6–39) |
| 5 y | 12 (5–22) | 9 (1–31) | 13 (3–30) | 10 (4–20) | 13 (2–34) | 15 (4–33) |
| Overall survival | ||||||
| No. of patients with events (%) | 39 (49) | 15 (54) | 11 (44) | 39 (54) | 15 (60) | 11 (48) |
| Median (95% CI),c mo | 47.6 (28.6–NR) | 30.1 (22.5–NR) | 55.0 (17.6–NR) | 30.1 (21.4–55.0) | 29.5 (21.4–NR) | 51.2 (17.5–NR) |
| Overall survival probability,c % (95% CI) | ||||||
| 1 y | 79 (69–87) | 86 (66–94) | 79 (56–80) | 77 (65–85) | 84 (63–94) | 76 (52–90) |
| 2 y | 65 (53–74) | 68 (47–82) | 69 (46–84) | 61 (48–71) | 64 (42–79) | 66 (42–82) |
| 3 y | 52 (39–63) | 42 (23–61) | 64 (41–80) | 46 (34–58) | 37 (18–56) | 61 (37–78) |
| 4 y | 47 (35–59) | 42 (23–61) | 58 (34–76) | 41 (28–54) | 37 (18–56) | 54 (30–74) |
| 5 y | 42 (30–55) | 42 (23–61) | 43 (20–65) | 35 (22–49) | 37 (18–56) | 39 (16–61) |
CI, confidence interval; CR, complete response; DCR, disease control rate; NR, not reached; ORR, objective response rate; PFS, progression-free survival; PR, partial response.
a
180 mg once daily with 7-day lead-in at 90 mg.
b
90 mg twice daily or 180 mg once daily.
c
Kaplan-Meier estimates of duration of response, PFS, and overall survival.