Responses to Selpercatinib Still Impressive With Over 20 Months of Follow-Up in RET+ NSCLC

With extended follow-up, selpercatinib has maintained its efficacy and safety in patients with RET fusion-positive non-small cell lung cancer.

Alexander Drilon, MD

Alexander Drilon, MD

Durable and robust responses were observed with selpercatinib (Retevmo) in patients with RET fusion-positive non–small cell lung cancer (NSCLC) after extended follow-up in the LIBRETTO-001 clinical trial (NCT03157128). According to a report published in the Journal of Clinical Oncology, selpercatinib also achieved intracranial activity in these patients.1

“With longer follow-up and additional patients, selpercatinib continued to demonstrate marked efficacy, with a high objective response rate, continued durability of response, and substantial CNS activity, as well as a consistent safety profile,” wrote the study authors led by Alexander Drilon, MD, a medical oncologist and chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center.

These findings follow the achievement of a 64% (95% CI, 54-73) objective response rate (ORR) and a 17.5-month median duration of response (DOR) with selpercatinib in previously treated patients assessed during the primary analysis of LIBRETTO-001. Moreover, treatment-naïve patients had an ORR of 85% (95% CI, 70-94), with 90% of responses lasting at the 6-month mark. Mainly low-grade toxicities were observed with selpercatinib in the primary analysis.2

Results from the updated analysis of LIBRETTO-001 included 316 patients with RET fusion-positive NSCLC who were evaluated for 18 months or more. There were 64 patients who were treatment-naïve and 247 who were previously treated with chemotherapy.1

By independent review committee (IRC), the ORR observed with selpercatinib in the treatment-naïve population was 84% (95% CI, 73%-92%), with complete response (CRs) in 6% of patients. Partial responses (PRs) were observed in 78% of patients, while 9% had stable disease (SD), and 4% has progressive disease. The median DOR was 20.2 months (95% CI, 13.0 to not evaluated [NE]). Responses were ongoing in 40% of the treatment-naïve population at the time of data cutoff.

In terms of survival, the median progression-free survival (PFS) among treatment-naïve patients was 22.0 months (95% CI, 13.8 to NE). Thirty-five percent of these patents were alive and progression-free at a median follow-up of 21.9 months. The median overall survival (OS) was not estimable, but 69% (95% CI, 55%-80%) of treatment-naïve patients were alive at 2 years.

Among chemotherapy-pretreated patients, the ORR by IRC was 61% (95% CI, 55%-67%) with CRs in 7% of patients. PRs were seen in 54% of patients, 33% of patients had SD, and 3% had PD. The median DOR in the pretreated group was 28.6 months (95% CI, 20.4-NE).

The median PFS in the chemotherapy pretreated group was 24.9 months (95% CI, 19.3-NE). Thirty-eight percent of patients remained alive and progression-free at a median follow-up of 24.7 months. OS was also not estimable in the pretreated group, but 69% (95% CI, 62%-75%) of patients were alive at 2 years.

The full safety population of the study included 796 patients. The safety profile of selpercatinib was consistent with previous information with longer follow-up. The most common grade 3 or higher treatment-emergent adverse events (AEs) were hypertension (19.7%), alanine aminotransferase increase (ALT; 11.4%), aspartate aminotransferase increase (AST; 8.8%), diarrhea (5.0%), and electrocardiogram QT prolongation (4.8%). In terms of treatment-related AEs, the most common grade 3 or higher events were hypertension (13.2%),AST increase (6.3%), and ALT increase (.0%).

“Given the durable efficacy observed in patients with non–small-cell lung cancer, broad-based genomic profiling should be considered to identify patients with RET fusions who may benefit from selpercatinib,” wrote Drilon et al.


1. Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion–positive non–small-cell lung cancer: updated safety and efficacy from the registrational libretto-001 phase I/II trial.Published September 19, 2022. J Clin Oncol. doi:10.1200/JCO.22.00393

2. Drilon A, Oxnard GR, Tan DS, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med. 2020; 383(9): 813-824. doi: 10.1056/NEJMoa2005653

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