Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial

Griesinger, Frank; Curigliano, Giuseppe; Thomas, Michael; Subbiah, Vivek; Baik, Christina S.; Tan, Daniel S.W.; Lee, D.H.; Misch, Daniel; Garralda, Elena; Kim, D.-W.; Wekken, A.J. van der; Gainor, Justin F.; Paz‐Ares, Luis; Liu, S.V.; Kalemkerian, Gregory P.; Houvras, Yariv; Bowles, Daniel W.; Mansfield, Aaron S.; Lin, Jessica J.; Smoljanović, Vlatka; Rahman, Ahmadur; Kong, Shengchun; Zalutskaya, Alena; Louie-Gao, Melinda; Boral, Andy

doi:10.1016/j.annonc.2022.08.002

Cited by 106 publications

(73 citation statements)

References 26 publications

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“…Among patients with RET fusion-positive NSCLC in the safety population ( n = 281), the most frequently reported TRAEs were neutropenia (46%), increased AST (41%), anemia (38%), leukopenia (34%), increased ALT (30%), constipation (26%), hypertension and fatigue (both 25%), and there was one TRAE (pneumonia) leading to death. 63 The most frequently reported grade ≥3 TRAEs were neutropenia (20%), anemia (12%), and hypertension (12%) 63 ( Table 2 ). At the latest data cutoff, discontinuation due to TRAEs was reported in 10% of patients, and the most common (≥10%) grade ≥3 AEs overall were anemia (23%), hypertension (18%), decreased neutrophil count (14%), pneumonia (13%), and neutropenia (11%).…”

Section: Potential Treatments For Ret Fusion-posit...mentioning

confidence: 99%

RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

et al. 2023

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The objective of this narrative review is to summarize the efficacy and safety of available therapies for rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), including in patients with central nervous system (CNS) metastases. Background information is provided on RET rearrangements in NSCLC and the molecular testing options available as well as an overview of clinical guidelines for molecular testing, which recommend broad molecular testing, including for RET rearrangements. The efficacy and safety of potential treatments for RET fusion-positive NSCLC, including multikinase inhibitors, RET-selective inhibitors, pemetrexed-based therapy, and immunotherapies are reviewed from Phase I/II and `real-world’ studies, alongside an overview of primary and secondary resistance mechanisms. The RET-selective inhibitors, selpercatinib and pralsetinib, are preferred first-line therapy options for patients with RET fusion-positive metastatic NSCLC and are recommended as subsequent therapy if RET inhibitors have not been used in the first-line setting.

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Section: Potential Treatments For Ret Fusion-posit...mentioning

confidence: 99%

RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

et al. 2023

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“…Nine patients with brain metastases showed an intracranial response rate of 56% in MTC ( 12 ). Remarkably, pralsetinib can be widely used regardless of RET fusion partner ( 62 ). Based on these data, pralsetinib was granted by the FDA in 2020 for RET mutation NSCLC and MTC.…”

Section: Ret Kinase Inhibitorsmentioning

confidence: 99%

A comprehensive overview of the relationship between RET gene and tumor occurrence

Zhao

Wang²,

Zhang³

et al. 2023

Front. Oncol.

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RET gene plays significant roles in the nervous system and many other tissues. Rearranged during transfection (RET) mutation is related to cell proliferation, invasion, and migration. Many invasive tumors (e.g., non-small cell lung cancer, thyroid cancer, and breast cancer) were found to have changes in RET. Recently, great efforts have been made against RET. Selpercatinib and pralsetinib, with encouraging efficacy, intracranial activity, and tolerability, were approved by the Food and Drug Administration (FDA) in 2020. The development of acquired resistance is inevitable, and a deeper exploration should be conducted. This article systematically reviewed RET gene and its biology as well as the oncogenic role in multiple cancers. Moreover, we also summarized recent advances in the treatment of RET and the mechanism of drug resistance.

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“…ARROW (86) is a 13-country, multi-cohort, open-label phase I/II trial. On August 13, 2022, Griesinger et al updated their latest analysis (87). A total of 281 RET fusionpositive NSCLC patients were involved between March 17, 2017, and November 6, 2020.…”

Section: Selective Ret Fusion-positive Inhibitorsmentioning

confidence: 99%

Targeted therapy of RET fusion-positive non-small cell lung cancer

Shen

Qiu

et al. 2022

Front. Oncol.

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Lung cancer has very high morbidity and mortality worldwide, and the prognosis is not optimistic. Previous treatments for non-small cell lung cancer (NSCLC) have limited efficacy, and targeted drugs for some gene mutations have been used in NSCLC with considerable efficacy. The RET proto-oncogene is located on the long arm of chromosome 10 with a length of 60,000 bp, and the expression of RET gene affects cell survival, proliferation, growth and differentiation. This review will describe the basic characteristics and common fusion methods of RET genes; analyze the advantages and disadvantages of different RET fusion detection methods; summarize and discuss the recent application of non-selective and selective RET fusion-positive inhibitors, such as Vandetanib, Selpercatinib, Pralsetinib and Alectinib; discuss the mechanism and coping strategies of resistance to RET fusion-positive inhibitors.

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Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial

Cited by 106 publications

References 26 publications

RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

A comprehensive overview of the relationship between RET gene and tumor occurrence

Targeted therapy of RET fusion-positive non-small cell lung cancer

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