2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Time-to-treatment discontinuation (TTD) and real-world progression-free survival (rwPFS) as endpoints for comparative efficacy analysis between entrectinib trial and crizotinib real-world ROS1 fusion-positive (ROS1+) NSCLC patients.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #393)
J Clin Oncol 37, 2019 (suppl; abstr 9070)
Author(s): Robert Charles Doebele, Laura Perez, Huong Trinh, Michael Martinec, Reynaldo Martina, Todd Riehl, Matthew Krebs, Neal J. Meropol, William Bruce Wong, Gracy Crane; University of Colorado, Denver, CO; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Genentech, South San Francisco, CA; University of Liverpool, Liverpool, United Kingdom; Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom; Flatiron Health, New York, NY; F. Hoffmann-La Roche Ltd, Welwyn Garden City, United Kingdom
Background: Entrectinib is an oral tyrosine kinase inhibitor for ROS1+ NSCLC. Three phase 1/2 single-arm studies showed entrectinib efficacy in this population (Doebele WCLC 2018). Due to the rarity of ROS1+ pts generating direct comparative evidence in prospective randomized trials is difficult. We identified a retrospective real-world cohort of ROS1+ NSCLC pts from electronic health records (EHR), to compare crizotinib, the current standard of care, to entrectinib as reported in clinical trials. Methods: Crizotinib-treated pts with advanced ROS1+ NSCLC diagnosed 1 Jan 2011 to 30 Jun 2018, were identified with technology-enabled abstraction in the Flatiron Health EHR-derived database ( > 2.1 million cancer pts from US oncology practice). Entrectinib trial inclusion/exclusion criteria were applied to match the crizotinib cohort as closely as possible. Primary endpoint: TTD, adapted from Gong (ASCO 2018); rwPFS (physician/scan report) and OS were secondary outcomes. Time-to-event analyses used Kaplan-Meier survival curves and Cox proportional hazard models on propensity score weighted populations; age, gender, race/ethnicity, smoking status, brain metastasis and previous lines of therapy were prognostic factors. Results: We analyzed 53 entrectinib and 69 crizotinib ROS1+ NSCLC pts. Median weighted TTD: entrectinib, 14.6 mo (95% CI: 8.3–23.8); crizotinib, 8.8 mo (95% CI: 8.2–9.9). When rwPFS from crizotinib was compared to trial PFS, entrectinib had longer PFS vs crizotinib (weighted HR: 0.44; 95% CI: 0.27–0.74). Median OS with entrectinib was not reached (median follow-up: 15.5 mo); weighted median OS with crizotinib was 18.5 mo (95% CI: 15.1–19.9). Findings were consistent across multiple sensitivity analyses. Conclusions: Entrectinib was associated with longer TTD and PFS in ROS1+ NSCLC pts vs a matched real-world crizotinib population. Control populations derived from real-world cohorts can supplement evidence from clinical trials in settings where new standards of care are needed, but where only limited data are available and randomization is not feasible.