ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data

Abstract

Objectives: ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients.

Methods: Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT).

Results: At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of which 27 were treated with third ALKi (group A) and 13 treated with chemotherapy (group B). mOS from third-line initiation was 27 months in group A (95% CI: 13-NR) and 13 months for group B (95% CI: 3-NR); the difference was not significant (NS; P = .12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, P = .002) and a higher number of ALKi (HR 0.38, 95% CI: 0.20-0.86, P = .011) associated significantly with longer OS of the third-line cohort. TNT was 10 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR); the difference was NS (P = .079).

Conclusion: We report mature real-world data of more than 4-year mOS in ALK-positive patients. The number of ALKi given was associated with a better outcome. OS and TNT demonstrated a statistically nonsignificant trend for a better outcome in patients receiving a third-line ALKi.

Keywords: ALK inhibitors; ALK rearrangement; non-small cell lung cancer; targeted therapy; third-line treatment.

Figure 1.

Overall survival of anaplastic lymphoma kinase-positive patients from diagnosis of metastatic disease; the full cohort. Median overall survival = 52 months (95% CI: 32-65).

Figure 2.

Overall survival from initiation of third-line of interest of anaplastic lymphoma kinase (ALK)-positive patients according to the treatment given as the third line of interest (ie, following 2 ALKi courses); further ALKi (group A) or chemotherapy (group B); third-line cohort (n = 40). Group A—median OS 27 months (95% CI: 13-NR). Group B—median OS 13 months (95% CI: 3-NR; P = .12).

Figure 3.

Time-to-next-treatment (TNT) of anaplastic lymphoma kinase (ALK)-positive patients according to the treatment given immediately following a second ALKi; further ALKi (group A) or chemotherapy (group B); third-line cohort (n = 40). Group A—median TNT 10 months (95% CI: 5-19). Group B—median TNT 3 months (95% CI: 0-NR). P = .079.