Study findings presented at the 2022 ASCO Annual Meeting show that selpercatinib is a safe and effective treatment option for patients with RET-altered non-small-cell lung cancer (NSCLC) and thyroid cancer, regardless of previous therapies or RET alteration type.

“Selpercatinib was the first RET-specific tyrosine kinase inhibitor approved by [the] FDA in RET-altered tumors,” wrote Mina Choudhry, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and colleagues, who conducted the systematic review and meta-analysis of existing literature and clinical trial data.

Using databases including PubMed, Embase, and clinicaltrials.gov the investigators reviewed 187 articles and 2 phase 1/2 clinical trials that pertained to selpercatinib therapy. Any studies or articles not expounding on the efficacy of selpercatinib in RET-altered tumors were excluded from the selection. R programming language was utilized for conducting the quantitative analysis.

In the 2 clinical trials (N = 309) 144 patients had advanced, RET-altered NSCLC and 162 had thyroid cancer. Among these patients, 143 had RET mutations and 163 had RET-fusions, 179 previously received systemic therapy, and 127 were treatment-naïve.

According to pooled data, overall, complete, and partial responses were observed in 72% (95% confidence interval [CI], 0.64-0.78; I²= 40%), 6% (95% CI, 0.03-0.13; I²= 49%), 66% (95% CI, 0.57-0.74; I²= 50%) of patients, respectively.

Furthermore, progressive stable disease rates were 3% (95% CI, 0.01-0.06; I²= 0) and 24% (95% CI, 0.18-0.30; I²= 22%), respectively.

Among pretreated and treatment-naïve patients, the pooled overall response rates were 67% (95% CI, 0.60-0.73; I²= 0) and 78% (95% CI, 0.64-0.87; I²= 51%), respectively, and for patients with RET-fusion tumors and RET-mutation tumors, the pooled overall response rates were 75% (95% CI, 0.58-0.87; I²= 68%) and 71% (95% CI. 0.63-0.78; I²= 0%), respectively.

When pooled, data on the incidence of grade ≥3 adverse events was 58% (95% CI, 0.43-0.72; I²= 85%). The researchers also observed a 10% (95% CI = 0.08-0.14, I²= 0) rise in alanine transaminase (95% CI, 0.08-0.14; I²= 0), 11% rise in aspartate transaminase (95% CI, 0.07-0.15; I²= 17).

Cases of diarrhea, hypertension, and QT abnormalities were reported in 5% (95% CI, 0.03-0.08; I²= 0), 17% (95% CI, 0.11-0.26; I²= 62%), and 4% (95% CI, 0.02-0.07; I²= 18%) of the patients, respectively.

“Selpercatinib was safe and effective in patients with RET-altered NSCLC and thyroid cancer regardless of prior treatment status and type of RET alteration. On indirect comparison, the safety profile with selpercatinib was better than previously used non-specific RET-inhibitors,” Dr Choudhry et al concluded.

There are 2 ongoing randomized clinical trials comparing selpercatinib with non-specific RET inhibitors and chemotherapy/PD-1 inhibitors (NCT04211337 and NCT04194944).

Source:

Choudhry M, Khan IW, Ali MJJ, et al. Efficacy and safety of selpercatinib in RET-altered tumors: A systematic review and meta-analysis. Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract 6091.