Abstract 3817: Real-world clinical outcomes in patients with advanced ROS1+non-small cell lung cancer in the US

Abstract Introduction: ROS1 rearrangements define a rare molecular subtype of non-small cell lung cancer (NSCLC), occurring in 1-2% of patients (pts) with advanced NSCLC (aNSCLC). Crizotinib and entrectinib received US approval for ROS1+ aNSCLC in March 2016 and August 2019, respectively. Few studies have addressed temporal trends in first-line (1L) utilization since these drugs’ approval. This study describes treatment patterns and clinical outcomes in pts with ROS1+ aNSCLC in the US. Methods: This retrospective study used the nationwide Flatiron Health (FH) electronic health record-derived de-identified database and included adult pts with ROS1+ aNSCLC who received 1L (index) therapy between March 2015 and December 2022. Pts were followed until March 31, 2023, and had ≥ 3 months of follow-up post-index date. Treatment-related (sequence, time to treatment discontinuation [TTD], time to next treatment [TTNT]) and clinical (real-world progression-free survival [rwPFS], overall survival [OS]) outcomes of 1L therapy were assessed using descriptive statistics and Kaplan-Meier methods. Results: In the FH database, 87,784 pts had aNSCLC, and 242 were ROS1+. The median age was 65 years; most were female (64%), White (67%), non-squamous (91%) and had a history of smoking (52%), with most pts having ECOG performance status 0 (31%) or 1 (35%). 19% had brain metastases prior to or up to 30 days post-index. Median follow-up time was 14.2 months. In 1L treatment, only 59% received ROS1-sensitive TKI monotherapy (i.e. crizotinib, entrectinib, ceritinib), with 97 (40%) and 40 (17%) treated with crizotinib and entrectinib monotherapy, respectively. Median TTD and TTNT for 1L was 6.4 (95% CI: 5.0, 7.6) and 7.6 (95% CI: 6.5, 9.4) months, respectively. Among 1L crizotinib pts, 51% had 2L treatments and 57% of those initiated another ROS1-sensitive TKI (16% entrectinib). Among 1L entrectinib pts, 43% had 2L therapy; of these, 82% initiated another ROS1-sensitive TKI. Median rwPFS was 7.5 (95% CI: 6.2, 9.3) months (1L crizotinib, 8.6 [95% CI: 5.3, 13.0] months; 1L entrectinib, 8.0 [95% CI: 5.3, 13.6] months). Median OS was 29.0 (95% CI: 19.4, 35.9) months (1L crizotinib, 31 [95% CI: 19.4, not estimable [NE]] months; 1L entrectinib, NE). Patients initiated ROS1-sensitive TKIs (crizotinib, entrectinib or ceritinib) in 1L across each year of the study (2015: 67%, 2016: 58%, 2017: 51%, 2018: 47%, 2019: 63%, 2020: 81%, 2021: 52%, 2022: 68%). Overall, 5% received checkpoint-inhibitor (CPI) only, 17% chemotherapy alone, and 7% a chemotherapy/CPI combination. Conclusion: Compared to relevant clinical trials, ROS1+ aNSCLC pts in this real-world study were older, had greater smoking exposure, and worse overall survival. Only 59% of pts initiated 1L ROS1-sensitive TKI monotherapy. These results highlight potential disparities in the diagnosis and treatment of ROS1+ NSCLC and opportunities for improving clinical outcomes. Citation Format: Reginald Villacorta, Saurabh Ray, Yong Yuan, Sushupta Vijapur, Sonia Kim, Haiyan Sun, Sky Myers, Vincent Lam. Real-world clinical outcomes in patients with advanced ROS1+non-small cell lung cancer in the US [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3817.