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
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract