Citations 1
Retreatment with First-Generation Selective RET Inhibitors in RET -Rearranged NSCLC Pretreated with Selpercatinib or Pralsetinib: Results from the RET-MAP Registry
Marinello, A., Rotow, Julia K., Lomibao, Meghanne , Miliziano, Daniela , Leporati, Rita , Feng, Jamie , Metro, Giulio , Brandão, Mariana , Gorría, Teresa , Nassar, Amin H. , Fila, Matteo, Fallet, V., Ricciuti, Biagio, Taylor, Skyler, Remon, Jordi, Planchard, David, Florez, Narjust, Besse, Benjamin, Drilon, Alexander D., Aldea, Mihaela, Nassar, Amin H. , Rotow, Julia , Metro, Giulio , Marinello, Arianna , Marinello, Arianna , Rotow, Julia K. , Citarella, Fabrizio , Fila, Matteo , Fallet, Vincent , Ricciuti, Biagio , Taylor, Skyler , Remon, Jordi , Planchard, David , Duma, Narjust , Besse, Benjamin , Drilon, Alexander , Aldea, Mihaela , Feng, Jamie , Citarella, Fabrizio , Ricciuti, Biagio , Planchard, David , Florez, Narjust , Besse, Benjamin , Aldea, Mihaela
Clinical Cancer Research | April 7, 2026 | Volume: 32 | Issue: 13 | Pages: 2637-2643
Abstract Purpose: In RET-rearranged non–small cell lung cancer (NSCLC), treatment options after first-generation selective RET inhibitors (SRI) 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 (AE). Results: Among 41 patients, 14 (34%) discontinued the initial SRI because of toxicity and 27 (66%) because of 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 reoccurred in nine patients (64%), with grade ≥3 AEs in 3 (21%) who switched at full dose. Among patients who discontinued because of 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 oligoprogressive disease 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 seems limited overall. However, selected patients, such as those with brain-only or oligoprogressive disease, may derive benefit.