Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

Efficacy of Selpercatinib by RET Fusion Partner in RET+ NSCLC: Results from the LIBRETTO-001 and LIBRETTO-431 Trials (#261)

Ben Solomon 1 , Alexander Drilon 2 , Keunchil Park 3 , Silvia Novello 4 , Ernest Nadal 5 , Benjamin Besse 6 , Nir Peled 7 , Patrick Peterson 8 , Scott Barker 8 , Anna M. Szpurka 8 , Olivera Grbovic-Huezo 8 , Herbert H. Loong 9 , Aarohan Pruthi 8
  1. Peter MacCallum Cancer Institute, Melbourne, Australia
  2. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
  3. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul , South Korea
  4. University of Turin, AOU San Luigi-Orbassano, Italy
  5. Institut Català d’Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain
  6. Institut Gustave Roussy, Villejuif, France
  7. Soroka University Medical Center, Beer-Sheva, Israel
  8. Eli Lilly, Indianapolis, IN, USA
  9. The Chinese University of Hong Kong, Hong Kong, China

Selpercatinib is a potent CNS active RET-inhibitor approved for treatment of advanced RET-driven cancers, including non-small-cell lung cancer (NSCLC).  Here, the relationship between selpercatinib efficacy and RET fusion partner was examined in a combined cohort of untreated and previously treated patients from phase 1/2 LIBRETTO-001 (NCT03157128) and untreated patients from phase 3 LIBRETTO-431 (NCT04194944).

LIBRETTO-431 patients were included in a separate controlled analysis of selpercatinib treatment versus platinum/pemetrexed chemotherapy +/- pembrolizumab (control), which was limited to KIF5B-RET due to low numbers of patients with other fusion partners. RET fusion partners were primarily identified in tumor tissue by NGS.  

Of the 415 patients who received selpercatinib, 263 were previously treated for advanced disease. The most commonly identified RET fusion partners were KIF5B-RET (71.6%)/CCDC6-RET (21.2%).  In KIF5B-RET fusions, the median PFS was 19.4 months (95% CI:17.1-22.7), while mPFS was not reached CCDC6-RET fusions. The ORR in patients with KIF5B-RET and CCDC6-RET was 65.3% (95% CI:59.6-70.7) and 83.0% (95% CI:73.4-90.1) respectively. The median DOR was 20.3 months (95% CI:17.5-23.9) in KIF5B-RET fusions, while not yet reached in CCDC6-RET fusions. Among LIBRETTO-431 patients, 44.0% (70/159) patients in the selpercatinib group and 49.0% (50/102) patients in the control group had KIF5B-RET. In KIF5B-RET fusions, the median PFS was 19.1 months (95% CI:13.9-24.8) with selpercatinib compared to 7.4 months (95% CI:4.9-11.2) with control.

In patients with RET+ NSCLC from LIBRETTO-001 and LIBRETTO-431, selpercatinib demonstrated robust and durable efficacy regardless of fusion partner. PFS in patients with KIF5B-RET from the LIBRETTO-431 control arm was consistent with prior reports of a poorer prognosis, regardless of treatment; however, clinical outcomes improved with selpercatinib versus chemotherapy +/- pembrolizumab. These data support early and comprehensive genomic testing to identify RET fusions and use selpercatinib as the first-line therapy in patients with advanced RET+ NSCLC.

Previously presented at WCLC 2024.