Efficacy and safety of pralsetinib in patients with advanced <i>RET</i> fusion‐positive non–small cell lung cancer

Zhou, Qing; Zhao, Jun; Chang, Jianhua; Wang, Huijie; Fan, Yun; Wang, Ke; Wu, Gang; Nian, Weiqi; Sun, Yehuan; Sun, Meili; Wang, Xiangcai; Shi, Huaqiu; Zheng, Xiangqian; Yao, Sheng; Qin, Mengmeng; Shen, Zhenwei; Yang, Jason; Wu, Yi‐Long

doi:10.1002/cncr.34897

Cited by 8 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 42 The efficacy results of pralsetinib in Chinese patients were consistent with those reported in the global population. 43 …”

Section: Treatments For Ret Fusion Nsclcmentioning

confidence: 99%

Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China

Pu,

Xu,

Wang

et al. 2023

Thoracic Cancer

View full text Add to dashboard Cite

The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

show abstract

“… 42 The efficacy results of pralsetinib in Chinese patients were consistent with those reported in the global population. 43 …”

Section: Treatments For Ret Fusion Nsclcmentioning

confidence: 99%

Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China

Pu,

Xu,

Wang

et al. 2023

Thoracic Cancer

View full text Add to dashboard Cite

show abstract

“…In September 2020, PRL was approved in the US for the treatment of metastatic RET fusion-positive NSCLC as detected by a Food and Drug Administration (FDA) approved test ( 7 , 9 ). PRL has demonstrated impressive and long-lasting efficacy, making it the novel standard of care for individuals with RET fusion-positive NSCLC, particularly in the multi-cohort, open-label phase I/II registrational trial ARROW ( 10 , 11 ). However, given its high cost of nearly $22,371.60 per month, information regarding the costs and effectiveness of PRL can aid in determining clinical practices and coverage decisions ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis

Liu,

Huo,

et al. 2023

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. Methods A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. Conclusions Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.

show abstract

The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis

Ke,

Huang,

Jing

et al. 2023

Invest New Drugs

View full text Add to dashboard Cite

Background Rearranged during transfection (RET) fusion-positive occurs in approximately 2% of non-small cell lung cancer (NSCLC). This mutation often predicts metastasis risk and poor prognosis, and current mainstream therapies provide limited patient benefit. Selective RET inhibitors Pralsetinib and Selpercatinib are targeted drugs approved by the US Food and Drug Administration for treating RET-mutated tumors. The phase I/II clinical trial results of their treatment of NSCLC have been published. However, the clinical effect of selective RET inhibitors on RET fusion-positive NSCLC remains controversial. Purpose Meta-analysis was performed to investigate the efficacy and safety of selective RET inhibitors in treating RET fusion-positive NSCLC. Methods Qualified literature was searched in Pubmed, Cochrane Library, Embase, and Web of Science. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), disease control rate (DCR), intracranial ORR, and adverse events. Stata 15.1 software was used to analyze the data. Results A total of 8 studies were included in this meta-analysis. The combined results showed that the ORR of patients treated with selective RET inhibitors was 67% (95% confidence interval:0.64 to 0.70, P < 0.01), DCR was 92% (95%CI: 0.91–0.94, P < 0.01), the mPFS was 16.09 months (95%CI: 11.66–20.52, P < 0.01). In treated patients with RET mutation, the intracranial ORR was 86% (95%CI:0.74 ~ 0.96, P < 0.01). ORR in untreated patients was more effective than untreated patients [HR = 0.44 (95%CI: 0.35–0.56, P < 0.01)]. The major adverse events (grade 3–4) are neutropenia (13%) and anaemia (13%). Conclusions Selective RET inhibitors Pralsetinib and Selpercatinib have shown a good effect on RET fusion-positive NSCLC, with a low incidence of adverse events.

show abstract

Efficacy and safety of pralsetinib in patients with advanced RET fusion‐positive non–small cell lung cancer

Cited by 8 publications

References 37 publications

Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China

Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China

First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis

The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis

Contact Info

Product

Resources

About