Treatment of patients with ALK-EML4 gene rearrangement with ALK inhibitors (ALK-I) yields high response rate (RR) and prolonged progression free survival (PFS). Defining progressive disease (PD) using RECIST has been challenging in the era of targeted and immunotherapy, as some patients are perceived to be deriving ongoing benefit despite PD by RECIST. We explore the impact of treatment beyond progression with ALK-I on patient symptoms and treatment duration.
Patients with advanced ALK-rearranged lung cancer treated at the Princess Margaret Cancer Centre between 2009 and 2017 were identified. Treatment duration was obtained from medical records, assessment of PFS by RECIST 1.1 from patient imaging, and patient self-reported symptoms and performance status (Edmonton Symptom Assessment Scale (ESAS), ECOG PS) were collected prospectively.
66 patients were identified with advanced ALK-rearranged lung cancer. The median age at diagnosis was 61 years, 49% were male, 78% presented with stage 4 disease, 47 received ALK-I therapy (median 2 lines, range 1-4). Over half (26/47, 55%) continued ALK-I treatment beyond RECIST PD. PD occurred most commonly in brain (15/47), lung and/or pleura (11/47); 17/47 received local therapy (predominantly radiation) and continued ALK-I. Data on time to RECIST PD and treatment failure are shown below. Only 34/47 patients had symptom data available at baseline, 22 with severe symptoms; 70% improved with initial ALK-I treatment. At the time of RECIST PD, most of those continuing ALK-I beyond progression had not experienced deterioration of symptoms.Table:
1347P ALK-I Treatment Patterns
|Initial ALK-I (N = 47)||Second ALK-I (N = 26)|
|Median Time to RECIST PD||10.1 months (range 0.3-– NR)||4.8 months (range 0.5 – NR)|
|Pts continuing ALK-I beyond PD||17/47 (36%)||8/26 (30%)|
|Median duration of treatment beyond progression||5.0 (range 0.6 – NR)||3.9 (range 1.3-21.5)|
NR- not reached.
Treatment beyond disease progression for patients with advanced lung cancer harboring ALK rearrangement is common and is often associated with maintenance of symptom burden.
Clinical trial identification
Legal entity responsible for the study
UHN, University of Toronto
All authors have declared no conflicts of interest.