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
1757 - Development of chimeric antigenic receptor (CAR) against VEGFR2 for solid tumor treatment
Presenter: Li-Shuang Ai
Session: Poster Display session 1
Resources:
Abstract
4156 - Triple blockade of EGFR, MEK and PD-L1 as effective antitumor treatment in PD-L1 overexpressing, MEK inhibitor resistant colon cancer cells.
Presenter: Nunzia Matrone
Session: Poster Display session 1
Resources:
Abstract
2949 - EGFR-mediated PD-L1 upregulation in HER2+ breast cancer (BC) cell line models
Presenter: Nicola Gaynor
Session: Poster Display session 1
Resources:
Abstract
4270 - The impact of cortisol on immune cells and its effect on cancer-immune cells co-culture in a 3D spheroid of ovarian cancer
Presenter: Maysa Al-natsheh
Session: Poster Display session 1
Resources:
Abstract
1568 - Application of sonoporation to increase anticancer drug efficacy in 2D and 3D NSCLC cell cultures
Presenter: Vilma Petrikaite
Session: Poster Display session 1
Resources:
Abstract
5400 - Tr1-like cells in human peripheral blood are part of the T effector memory pool and are preferentially stimulated via CD55
Presenter: Iniobong Charles
Session: Poster Display session 1
Resources:
Abstract
5817 - Functional analysis of tumor infiltrating lymphocytes in triple negative breast cancer focusing on granzyme B
Presenter: Hitomi Kawaji
Session: Poster Display session 1
Resources:
Abstract
2287 - Aberrant glycolysis associates with inflammatory tumor microenvironment and promotes metastasis in triple-negative breast cancer
Presenter: Chengwei Lin
Session: Poster Display session 1
Resources:
Abstract
735 - Anti-cancer effects of differentiation-inducing factor-1 in triple negative breast cancer.
Presenter: Fumi Tetsuo
Session: Poster Display session 1
Resources:
Abstract
2105 - The Inhibitory Effect in Oral Squamous Cell Carcinoma Cells by Knocking down Matrix Metalloproteinase 9
Presenter: Xinyan Zhang
Session: Poster Display session 1
Resources:
Abstract