Abstract 5239
Background
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.
Methods
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.
Results
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).Table:
1546P
| 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) |
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).
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Nicola Griffin of Gardiner-Caldwell Communications, funded by F. Hoffmann-La Roche.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
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.
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