Retreatment with First-Generation Selective RET Inhibitors in RET-Rearranged NSCLC Pretreated with Selpercatinib or Pralsetinib - Results from the RET-MAP Registry.
[PURPOSE] In RET-rearranged non-small cell lung cancer (NSCLC), treatment options after first-generation selective RET inhibitors (SRIs) are limited, and the value of SRI retreatment remains unclear.
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APA
Marinello A, Rotow JK, et al. (2026). Retreatment with First-Generation Selective RET Inhibitors in RET-Rearranged NSCLC Pretreated with Selpercatinib or Pralsetinib - Results from the RET-MAP Registry.. Clinical cancer research : an official journal of the American Association for Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-4814
MLA
Marinello A, et al.. "Retreatment with First-Generation Selective RET Inhibitors in RET-Rearranged NSCLC Pretreated with Selpercatinib or Pralsetinib - Results from the RET-MAP Registry.." Clinical cancer research : an official journal of the American Association for Cancer Research, 2026.
PMID
41945500
Abstract
[PURPOSE] In RET-rearranged non-small cell lung cancer (NSCLC), treatment options after first-generation selective RET inhibitors (SRIs) are limited, and the value of SRI retreatment remains unclear. This study evaluates outcomes of SRI retreatment.
[EXPERIMENTAL DESIGN] This multicenter retrospective study included patients with advanced RET-rearranged NSCLC who received ≥2 SRI-based therapy lines. Of 411 SRI-treated patients, 41 (10%) underwent SRI retreatment. Outcomes included objective response rate (ORR), progression-free survival (PFS), 6-month PFS, time to treatment failure, adverse events (AEs).
[RESULTS] Among 41 patients, 14 (34%) discontinued the initial SRI due to toxicity and 27 (66%) due to progression. After discontinuation for toxicity, all switched to an alternate SRI, achieving an ORR of 67%, median PFS of 9.9 months, and 6-month PFS of 80.3%. AEs re-occurred in 9 patients (64%), with grade ≥3 AEs in 3 (21%) who switched at full dose. Among patients who discontinued for progression, SRI monotherapy (n=13) achieved an ORR of 23%, median PFS of 7 months, and 6-month PFS of 61.5%. Benefit was observed in patients with brain-only or oligo-progression, or dose reduction on first SRI. Combination therapy (n=14; targeted agents, n=11; chemotherapy, n=3) achieved an ORR of 39%, median PFS of 4 months and 6-month PFS of 27.3%.
[CONCLUSIONS] Same-class SRI switch after toxicity is feasible and clinically active but warrants cautious, dose-adjusted switching to mitigate toxicities. The efficacy of SRI rechallenge after progression appears limited overall. However, selected patients, such as those with brain-only or oligoprogressive disease, may derive benefit.
[EXPERIMENTAL DESIGN] This multicenter retrospective study included patients with advanced RET-rearranged NSCLC who received ≥2 SRI-based therapy lines. Of 411 SRI-treated patients, 41 (10%) underwent SRI retreatment. Outcomes included objective response rate (ORR), progression-free survival (PFS), 6-month PFS, time to treatment failure, adverse events (AEs).
[RESULTS] Among 41 patients, 14 (34%) discontinued the initial SRI due to toxicity and 27 (66%) due to progression. After discontinuation for toxicity, all switched to an alternate SRI, achieving an ORR of 67%, median PFS of 9.9 months, and 6-month PFS of 80.3%. AEs re-occurred in 9 patients (64%), with grade ≥3 AEs in 3 (21%) who switched at full dose. Among patients who discontinued for progression, SRI monotherapy (n=13) achieved an ORR of 23%, median PFS of 7 months, and 6-month PFS of 61.5%. Benefit was observed in patients with brain-only or oligo-progression, or dose reduction on first SRI. Combination therapy (n=14; targeted agents, n=11; chemotherapy, n=3) achieved an ORR of 39%, median PFS of 4 months and 6-month PFS of 27.3%.
[CONCLUSIONS] Same-class SRI switch after toxicity is feasible and clinically active but warrants cautious, dose-adjusted switching to mitigate toxicities. The efficacy of SRI rechallenge after progression appears limited overall. However, selected patients, such as those with brain-only or oligoprogressive disease, may derive benefit.