Dr Riess on Treatment Developments in ALK+ and ROS1+ NSCLC

Jonathan Wesley Riess, MD, MS, director, Thoracic Oncology, associate professor, medicine, Division of Hematology and Oncology, University of California, Davis Comprehensive Cancer Center, discusses developments in the treatment of patients with non–small cell lung cancer (NSCLC) harboring ALK or ROS1 rearrangements.

Several advances have been made in the frontline management of both ROS1- and ALK-rearranged NSCLC, Riess states.

Long-term follow-up data from the phase 3 CROWN trial (NCT03052608) investigating lorlatinib (Lorbrena) in patients with advanced ALK-positive NSCLC were presented at the 2024 ASCO Annual Meeting by Benjamin J. Solomon, PhD, MBBS, of Peter MacCallum Cancer Centre. In this trial, lorlatinib (n = 149) elicited a 5-year progression-free survival (PFS) rate of 60% vs 8% with crizotinib (Xalkori; n = 147). At a median follow-up of 60.2 months (95% CI, 57.4-61.6), the median PFS was not reached (NR; 95% CI, 64.3%-NR) with lorlatinib vs 9.1 months (95% CI, 7.4-10.9) with crizotinib (HR, 0.19; 95% CI, 0.13-0.27). This PFS benefit with lorlatinib was observed across prespecified patient subgroups, including patients with baseline brain metastases (HR, 0.08; 95% CI, 0.04-0.19). Among these patients, the median PFS was NR (95% CI, 32.9 months-NR) with lorlatinib vs 6.0 months (95% CI, 3.7-7.6) with crizotinib.

In November 2023, repotrectinib (Augtyro) was approved by the FDA for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC. Data published in January 2024 in The New England Journal of Medicine showed that evaluable patients in the pivotal phase 1/2 TRIDENT-1 trial (NCT03093116) who received repotrectinib and had not previously received a ROS1 TKI (n = 71) achieved a median PFS of 35.7 months (95% CI,27.4-not estimable). The 18-month estimated PFS rate was 70% (95% CI, 59%-81%) in this population. Among the patients who had previously received a ROS1 TKI and had no prior exposure to chemotherapy (n = 56), the median PFS was 9.0 months (95% CI, 6.8-19.6), and the 12-month estimated PFS rate was 41% (95% CI, 27%-56%).