ALK inhibitors (ALKi) have shown substantial benefit in pts with advanced ALK+ NSCLC. We describe real-world treatment patterns and outcomes in pts with ALK+ advanced NSCLC in the US.
This retrospective cohort study utilised US electronic health record data from Flatiron Health. Pts diagnosed with stage IIIB-IV ALK+ NSCLC from 1 Jan 2011 to 30 Sep 2018 were included. Treatment patterns and outcomes (real-world progression-free survival [rwPFS] and overall survival [OS]) were extracted for first- or second-line therapy. Time to treatment discontinuation (TTTD) was used as a surrogate for real-world treatment duration accounting for treatment beyond progression. Time-to-event analyses were performed using Kaplan-Meier methods.
Data were available for 620 pts with ALK+ advanced NSCLC. An ALKi was given to 420/620 (67.7%) pts as first-line therapy and 273/359 (76.0%) pts who received second-line therapy. Among non-ALKi treatments, platinum-based regimens were the most common. Crizotinib was the preferred first-line ALKi up to 2016, and then alectinib. As second-line therapy, crizotinib was the preferred ALKi up to 2013, followed by ceritinib from 2014–2015, and then alectinib to the end of the follow-up period. TTTD, rwPFS and OS were longest with alectinib, followed by crizotinib and non-ALKi (Table). 1546P 1L, first-line therapy; 2L, second-line therapy; ALKi, ALK inhibitor; rwPFS, real-world progression-free survival; TTTD, time to treatment discontinuation; OS, overall survival; NR, not reached (median survival estimate could not be calculated).1L Outcome Statistics Alectinib (n = 98) Ceritinib (n = 4) Crizotinib (n = 318) non-ALKi (n = 200) rwPFS Median (95% CI), months NR 5.06 (0.72, NR) 6.41 (5.92, 8.16) 8.26 (6.25, 9.9) 6-month probability (95% CI) 0.83 (0.75, 0.91) 0.5 (0.19, 1) 0.55 (0.49, 0.6) 0.59 (0.52, 0.66) 12-month probability (95% CI) 0.68 (0.58, 0.79) 0.25 (0.05, 1) 0.32 (0.27, 0.38) 0.37 (0.3, 0.44) TTTD Median (95% CI), months NR 6.1 (0.72, NR) 7.57 (6.97, 9.14) 3.12 (2.76, 4.38) 6-month probability (95% CI) 0.85 (0.78, 0.92) 0.5 (0.19, 1) 0.61 (0.56, 0.67) 0.35 (0.29, 0.43) 12-month probability (95% CI) 0.73 (0.64, 0.84) 0.25 (0.05, 1) 0.36 (0.31, 0.42) 0.21 (0.16, 0.28) OS Median (95% CI), months NR 6.1 (0.72, NR) 23.06 (16.51, 30.86) 27.99 (21.6, 36.51) 6-month probability (95% CI) 0.92 (0.87, 0.98) 0.5 (0.19, 1) 0.78 (0.73, 0.82) 0.84 (0.79, 0.89) 12-month probability (95% CI) 0.85 (0.77, 0.93) 0.25 (0.05, 1) 0.65 (0.6, 0.7) 0.71 (0.65, 0.78) 2L Outcome Statistics Alectinib (n = 90) Ceritinib (n = 75) Crizotinib (n = 97) non-ALKi (n = 86) rwPFS Median (95% CI), months 13.59 (10.33, NR) 6.32 (4.64, 8.45) 6.88 (4.9, 9.87) 4.4 (2.96, 6.81) 6-month probability (95% CI) 0.76 (0.68, 0.86) 0.51 (0.4, 0.64) 0.54 (0.45, 0.65) 0.4 (0.31, 0.52) 12-month probability (95% CI) 0.55 (0.44, 0.68) 0.25 (0.16, 0.37) 0.35 (0.26, 0.46) 0.22 (0.14, 0.33) TTTD Median (95% CI), months 19.84 (14.54, NR) 8.19 (6.22, 11.84) 8.72 (7.37, 5.36) 4.61 (3.42, 6.18) 6-month probability (95% CI) 0.85 (0.77, 0.93) 0.61 (0.5, 0.73) 0.66 (0.57, 0.76) 0.39 (0.3, 0.51) 12-month probability (95% CI) 0.68 (0.58, 0.8) 0.34 (0.24, 0.47) 0.41 (0.32, 0.52) 0.18 (0.11, 0.28) OS Median (95% CI), months NR 16.84 (9.51, 33.75) 22.3 (17.17, 45.23) 15.56 (11.41, 26.94) 6-month probability (95% CI) 0.92 (0.86, 0.98) 0.75 (0.65, 0.86) 0.85 (0.78, 0.93) 0.71 (0.62, 0.82) 12-month probability (95% CI) 0.85 (0.77, 0.93) 0.59 (0.48, 0.71) 0.69 (0.6, 0.79) 0.56 (0.46, 0.68)
The use of ALKi in the US reflects current clinical guidelines. Despite the choice and established benefit of individual ALKi as first-line therapy, more than 25% of pts received a non-ALKi as first-line therapy, even in recent years (2017/2018). Furthermore, in clinical practice, treatment beyond progression with an ALKi is relatively common. OS for non-ALKi was comparable to some ALKi, but OS is also reflective of treatment received in later lines of therapy.
Nicola Griffin of Gardiner-Caldwell Communications, funded by F. Hoffmann-La Roche.
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
M.G. Krebs: Advisory / Consultancy: Achilles Therapeutics, Janssen, Octmet and Roche; Research grant / Funding (self): BerGenBio and Roche; Travel / Accommodation / Expenses: AstraZeneca and BerGenBio; Research grant / Funding (institution): AstraZeneca, Bayer, BerGenBio, Blueprint, Carrick, Immutep, Incyte, Janssen, Merck, Octimet and Roche. L. Polito: Full / Part-time employment: F. Hoffmann-La Roche Ltd. V. Smoljanović: Full / Part-time employment: F. Hoffmann-La Roche Ltd. H. Trinh: Full / Part-time employment: Genentech Inc. G. Crane: Full / Part-time employment: Genentech Inc.