In brief
- In the international RET-MAP registry, 81 of 207 patients given a first-line selective RET inhibitor stopped it because of disease progression, and 65 of them went on to further treatment.
- Second-line platinum-pemetrexed, with or without immunotherapy, was the most common choice (35 patients) and gave a real-world objective response rate of 41% (12 of 29).
- Median real-world progression-free survival (rwPFS) on that regimen was 6.1 months and median overall survival (OS) was 13.7 months.
- Chemotherapy alone (n=12) and chemo-immunotherapy (n=23) gave similar rwPFS (HR 1.05, p=0.903) and OS (HR 0.83, p=0.674).
- In the third line, taxane-based therapy was the most frequent treatment (n=11) and produced no responses, with a median rwPFS of 1.5 months.
Study at a glance
- Cohort: RET-MAP, an international real-world registry across 52 centres
- Population: 207 patients with RET fusion-positive metastatic NSCLC given a first-line selective RET inhibitor; 81 discontinued for progression
- Second line: platinum-pemetrexed alone (n=12) or with immunotherapy (n=23)
- Median follow-up: 53 months
- Response: real-world objective response rate 41% (12/29)
- Survival: median rwPFS 6.1 months (95% CI 4.8 to 11.4); median OS 13.7 months (95% CI 8.7 to 26.5)
- Third line (n=32): taxane with or without antiangiogenic therapy most common (n=11); no responses; median rwPFS 1.5 months
Selective RET inhibitors leave no established next step
Selective RET inhibitors are the first-line standard for RET fusion-positive NSCLC. No treatment has been established for patients whose disease progresses on them, and because the population is rare, single-arm trials in this setting have little real-world data to be compared against. The authors set out to provide that reference point.
Of the 207 patients in the registry who started on a selective RET inhibitor, 81 (39%) discontinued because of progression. Eighty percent of those (65 patients) received a subsequent therapy, and in 35 of them (54%) it was platinum-pemetrexed with or without immunotherapy.
A 41% response rate to second-line platinum-pemetrexed
The real-world objective response rate was 41%, or 12 of 29 patients. After a median follow-up of 53 months, the median rwPFS was 6.1 months and the median OS was 13.7 months. The 95% confidence intervals ran from 4.8 to 11.4 months for rwPFS and 8.7 to 26.5 months for OS.
All of these are real-world endpoints drawn from registry data. The abstract does not describe how or how often patients were imaged.
Similar rwPFS and OS with or without added immunotherapy
Twelve patients received chemotherapy alone and 23 received chemo-immunotherapy. Median rwPFS was 5.9 and 6.8 months respectively (HR 1.05, p=0.903), and median OS was 18.5 and 13.7 months (HR 0.83, p=0.674). The abstract describes the outcomes of the two groups as similar.
Three patients given chemo-immunotherapy remained progression-free for more than 24 months. All three had received the first-line selective RET inhibitor for only a short time.
“Third-line outcomes were poor, highlighting the need for new treatment strategies.”Miliziano et al., Clinical Cancer Research (2026)
No responses to taxane-based therapy in the third line
The third-line analysis covered 32 patients who had been exposed to both a selective RET inhibitor and platinum-pemetrexed, in either order. Taxane with or without antiangiogenic therapy was the most common regimen, given to 11 patients. None responded, and the median rwPFS was 1.5 months (95% CI 0.8 to not reached).
Sources
- Clinical Cancer Research. Second- and third-line outcomes after selective RET inhibitor failure in RET fusion-positive metastatic lung cancer: A real-world analysis from the RET-MAP registry (2026-10-14). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Antonio Calles, Jordi Remon, Alessio Cortellini, David Planchard and Biagio Ricciuti.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
