Pralsetinib and Selpercatinib Evaluated as Treatment for Patients with RET Gene Fusion–Positive NSCLC

Selpercatinib and pralsetinib are US Food and Drug Administration–approved treatment options for patients with RET fusion–positive NSCLC.

Selpercatinib and pralsetinib inhibit oncogenic RET alterations, which are targetable oncogenic drivers in multiple tumor types, including non–small-cell lung cancer (NSCLC).^1,2

Investigators in the global, multicenter phase 1/2 LIBRETTO-001 trial studied selpercatinib in patients with RET fusion–positive NSCLC.¹ Following the phase 1 dose-escalation portion of the trial, patients were treated with twice-daily oral selpercatinib 160 mg.¹ The primary study end point was objective response rate; secondary end points included duration of response and safety.¹

Among patients with NSCLC who were treated with a median of 3 prior systemic platinum-based regimens, treatment with selpercatinib resulted in an (investigator assessed) objective response rate of 70%.¹  Response rates did not differ by number or type of prior therapies or by fusion partner.¹ Median duration of response was 20.3 months with 62% of 73 responders censored at a median follow-up of 14.8 months.¹ The investigator-assessed objective response rate for the 39 treatment-naïve patients with NSCLC who received selpercatinib was 90% (including 2 responses pending confirmation at the time of data analysis).¹ Median duration of response was not reached; 82% of 33 confirmed responses were ongoing after follow-up of 7.4 months (median).¹

Dry mouth (33%), increased aspartate aminotransferase (25%), increased alanine aminotransferase (24%), hypertension (23%), diarrhea (20%), and fatigue (17%) were the most common TRAEs that occurred in ≥15% of the 702 patients who were treated with selpercatinib for any tumor type.¹ Two percent of patients discontinued selpercatinib for TRAEs.¹

In the phase 1/2 ARROW study, patients who were treated with once-daily oral pralsetinib 400 mg demonstrated an overall response rate of 73% in 26 treatment-naïve patients and 61% in 80 platinum-exposed patients who have RET fusion–positive NSCLC.² Overall response rate was similar regardless of prior therapies, central nervous system involvement, or RET fusion partner.²

In the safety population for pralsetinib (N = 354, including NSCLC and other tumor types), the majority of treatment-related adverse events (TRAEs) were grade 1 or grade 2.² These included increased aspartate aminotransferase (31%), anemia (22%), increased alanine aminotransferase (21%), constipation (21%), and hypertension (20%).² Four percent of patients discontinued pralsetinib due to TRAEs.²

Based on their marked and durable antitumor activity in patients with RET fusion–positive NSCLC, selpercatinib and pralsetinib were approved for use by the US Food and Drug Administration in 2020.^3,4

References
1. Goto K, et al. J Clin Oncol. 2020;38(suppl 15). Abstract 3584.
2. Gainor JF, et al. J Clin Oncol. 2020;38(suppl 15). Abstract 9515.
3. US Food and Drug Administration. FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutations-or-fusions. Accessed January 11, 2021.
4. US Food and Drug Administration. FDA approves pralsetinib for lung cancer with RET gene fusions. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-lung-cancer-ret-gene-fusions. Accessed January 11, 2021.