Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) in US clinical practice

Abstract

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).

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.

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).

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.