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.
Resources from the same session
4325 - Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: insights of the MATCH-R study
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract
2185 - Sequential treatment with afatinib followed by 3rd generation EGFR-TKI – subgroup analysis of the GIDEON trial: a prospective non-interventional study (NIS) in EGFR mutated NSCLC patients in Germany
Presenter: Wolfgang Brückl
Session: Poster Display session 1
Resources:
Abstract
1524 - Effectiveness of sequencing TKIs in patients with EGFR mutation-positive Non-small-Cell Lung Cancer (NSCLC): A French National medico administrative claim database analysis
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
5733 - Phase II study of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation: A multicenter trial of the Korean Cancer Study Group (LU17-19)
Presenter: Tae Min Kim
Session: Poster Display session 1
Resources:
Abstract
5440 - Different stories for different EGFR exon 19 deletion variants
Presenter: Chao Zhao
Session: Poster Display session 1
Resources:
Abstract
2982 - Safety and activity of alflutinib in patients with advanced EGFR T790M mutation non-small cell lung cancer who progressed after EGFR-TKI therapy
Presenter: Yuan-Kai Shi
Session: Poster Display session 1
Resources:
Abstract
4002 - Afatinib followed by osimertinib in patients with EGFR mutation-positive (EGFRm+) advanced NSCLC: updated data from the GioTag real-world study
Presenter: Maximilian Hochmair
Session: Poster Display session 1
Resources:
Abstract
2941 - Treatment patterns of EGFR mt+ NSCLC IV pts: Real world data of the NOWEL network
Presenter: Julia Roeper
Session: Poster Display session 1
Resources:
Abstract
4154 - TP53 mutations predicts worse prognosis in EGFR-mutated NSCLC patients receiving TKIs in first- or further line of treatment
Presenter: Matteo Canale
Session: Poster Display session 1
Resources:
Abstract
1175 - HER3 ligand heregulin expression and clinical implication in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors
Presenter: Kimio Yonesaka
Session: Poster Display session 1
Resources:
Abstract