Abstract 37P
Background
RET-fusion was reported contribute about 2% of acquired resistance mechanisms of EGFR/ALK-TKIs. Selective RET inhibitor pralsetinib demonstrated impressive improvement of survival in patients with RET+ aNSCLC in the I/II ARROW study. However, the efficacy in patients with acquired RET-fusion after resistance to EGFR/ALK-TKIs was only reported by case, and the strategy of overcome the acquired RET-fusion has not been fully investigated.
Methods
This multicenter, retrospective, real-world data analysis enrolled thirty-one aNSCLC with acquired RET-fusion after resistance to EGFR/ALK-TKIs in 23 centers across China from Jan 1st, 2015 to Nov 23rd, 2022. Cohort 1 including 20 patients who received pralsetinib immediately after RET-fusion was detected, of which 15 patients received pralsetinib combined with EGFR/ALK-TKI. Eleven patients who underwent standard chemotherapy in combination with or without immunotherapy or antiangiogenesis therapy on acquired RET+ occurred were enrolled in Cohort 2. Molecular profile, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), time to treatment failure (TTF), toxicity was assessed.
Results
25.8% (8/31) patients lost EGFR mutation when RET-fusion was detected. EGFR 19del (64.5%) was more likely to develop acquired RET+ compared with L858R mutation (29.0%). CCDC6 was the most common RET-partners (38.7%), followed by KIF5B (19.4%), and NCOA4 (16.1%). In Cohort 1, ORR was 35.0% and DCR was 75.0%, which were higher than Cohort 2 (18.2% and 54.6%, respectively). Patients who received pralsetinib-based therapy had a longer PFS and TTF compared with patients in cohort 2 (PFS: 8.42 months vs. 6.97 months, TTF: 6.48 months vs. 4.24 months). Pralsetinib and EGFR-TKI combination therapy was generally well tolerated, with AEs consistent with known profile of the two drugs.
Conclusions
Pralsetinib-based therapy may be a potential strategy to overcome the acquired RET-fusion after resistance of EGFR/ALK-TKIs.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.