Continuation of EGFR/ALK inhibition after local therapy of oligoprogressive disease in EGFR mutant (Mt) and ALK+ non-small cell lung cancer (NSCLC).

Abstract

7526 Background: This study aimed to investigate the benefits of local treatment of limited disease progression and continuation of crizotinib (C) or EGFR-TKI in patients with ALK+ or EGFR-Mt metastatic NSCLC, respectively. Methods: Patients with advanced ALK+ NSCLC treated with C (n=38) and EGFR-Mt NSCLC treated with EGFR TKIs (erlotinib or gefitinib) (n=27) were identified. Patients were evaluated for initial response, site of first progression (CNS or extra CNS (eCNS)) and median progression free survival (PFS1). A subset of patients with limited sites of progression (oligoprogressive disease) suitable for local therapy received either radiation or surgery to these sites and continued on the same TKI. The subsequent pattern of progression and median progression free survival from the time of first progression (PFS2) were recorded. Results: In 38 ALK+ patients, PFS1=9.0 months on C. In 27 EGFR-Mt patients, PFS1=13.8 months on EGFR-TKI. CNS was the first site of progression in 13/28 (46%) of ALK+ patients and 5/23 (22%) EGFR-Mt patients. 25 of 51 patients who progressed (49%) were deemed suitable for local therapy (15 ALK+, 10 EGFR-Mt; 24 with radiotherapy (Body: 3 XRT, 9 SBRT; CNS: 7 WBRT, 5 SRS), 1 with surgery (adrenalectomy)) and continuation of the same targeted therapy. 19/25 patients progressed post local therapy, median PFS2 = 6.2 months. In patients who progressed at PFS1 only in the CNS, there was a trend to longer PFS2 than patients who progressed at PFS1 in eCNS (7.1 months vs 4.0 months, p=0.26). 60% who progressed only in the CNS at PFS1, progressed eCNS at PFS2 (n=10). Conclusions: Progression of oncogene addicted NSCLC on relevant targeted therapies is often suitable for local therapy (oligoprogressive disease). Continuation of the targeted therapy following local therapy is associated with >6 months of additional disease control. [Table: see text]