36P Selpercatinib treatment beyond progression (PD) in RET fusion-positive NSCLC: Association with pattern of PD

Selpercatinib, a highly selective RET kinase inhibitor with CNS activity, is approved in multiple countries for patients (pts) with RET fusion-positive NSCLC. In other oncogene-addicted NSCLC settings, targeted treatment beyond RECIST progression (PD) in the case of oligo-progression (oligoPD) is commonly utilized and endorsed by guidelines. We hypothesized that the pattern of PD would be associated with outcomes on post-PD therapy. NSCLC pts were treated on the phase I/II LIBRETTO-001 trial (NCT03157128) and were permitted to continue selpercatinib beyond investigator (INV) assessed PD if the pt derived ongoing benefit according to the INV and with sponsor approval. Data of pts with PD confirmed by Blinded Independent Central Review (BICR) were used for this analysis (n=80; data cut of 13JAN2023). OligoPD was defined as up to 5 progressing lesions (1-2 [limited] versus 3-5). 80 pts had BICR-confirmed PD and continued selpercatinib per INV assessment; 23 had widespread progression and 57 pts had oligoPD, including 20 pts with 1-2 progressing lesions and 37 pts with 3-5 progressing lesions. At study entry 11 pts out of 80 pts had CNS metastases. Median duration of treatment (mDoT) post-PD (Table) was longest in pts with limited oligoPD and shortest in pts with widespread PD. Post progression mDoT appeared comparable between pts who progressed in CNS only (n=8) versus pts with extracranial (n=68) PD. Of 80 pts with PD, 33 pts received local radiotherapy upon BICR confirmed progression, further analysis for whom is ongoing. No new safety signals were identified in this population.Table: 36PPD per BICRPts (n)mDoT prior to BICR PD (months)mDoT post-BICR PD (months)All pts treated post-PD809.05.9Pts with oligoPD5710.99.4Pts with 1-2 new/progressive lesions2010.514.6Pts with 3-5 new/progressive lesions3710.94.8Pts with widespread PD235.53.7Pts with CNS only PD810.47.5Pts with extracranial PD688.66.4 Open table in a new tab Continuing selpercatinib beyond progression may be considered based on INV assessed benefit, particularly for pts with limited oligoPD, including pts with CNS progression. Clinical judgement of ongoing benefit together with radiological imaging should be used to make the most appropriate decision for pts in the setting of PD.