Abstract 90P
Background
There is limited data about the efficacy of subsequent therapy following the progression of crizotinib in advanced ROS1+ NSCLC in real word setting.
Methods
Medical records of advanced ROS1+NSCLC patients who received subsequent therapy after the resistance of crizotinib were retrospectively collected in multiple tertiary-hospitals in China. Radiological evaluation was based on RECIST 1.1 (intracranial efficacy was also evaluated by RECIST 1.1, namely at most two target lesions (≥1 cm in MRI) could be chose). The following objective response rate (ORR) and intracranial-ORR was described in patients with target lesions in whole body or in brain.
Results
140 patients had detailed medical records of subsequent therapy following the progression of crizotinib. 99 patients received other ROS1-TKIs as their first subsequent targeted therapy. Next-generation ROS1-TKI (repotrectinib, taletrectinib, TL-139) demonstrated superior efficacy over non-next-generation TKI (PFS: 13.9 m vs 4.4 m, HR=0.46, 95%CI: 0.24–0.86, p=0.04; ORR: 70% vs 20%, p=0.002). ORR was 66.7% for patients carrying G2032R mutation treated with next-generation TKI while non-next-generation TKI presented dismal response in another 7 patients with secondary ROS1 mutation (G2032R, D2033N, L2026M, S1986F), only 1 patient with L2026M mutation showed response to lorlatinib, the rest of them demonstrated progressive disease. PFS was 8.9 months (95%CI: 3.3–14.6 m) and 3.4 months (95%CI: 3.1–3.8 m), ORR was 34.2% and 7.7%, intracranial-ORR (without simultaneous RT) was 50% and 0% for lorlatinib and entrectinib, respectively. Chemo+IO ± anti-VEGF therapy was no better than Platinum-Chemo plus anti-VEGF therapy (ORR: 63.2% vs 50%, p=0.41; PFS: 5.8 m vs. 8.2 m, HR=1.82, 95%CI: 0.86–3.83, p=0.07).
Conclusions
Next-generation ROS1-TKI should be the preferred subsequent choice after the resistance of crizotinib especially for patients with ROS1 secondary mutation. Lolatinib should also be considered particularly in patients with CNS metastases while entrectinib should no be routinely recommended. IO-based combination treatment was no better than traditional platinum-doublet chemo plus anti-VEGF therapy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.