Phase III Study of Selpercatinib Versus Chemotherapy ± pembrolizumab in Untreated
            <i>RET</i>
            Positive Non-Small-Cell Lung Cancer

Solomon, Benjamin; Zhou, C.; Drilon, Alexander; Park, Keunchil; Wolf, Jürgen; Elamin, Yasir Y.; Davis, Hannah M.; Soldatenkova, Victoria; Sashegyi, Andreas; Lin, Aimee Bence; Lin, Boris K.; Loong, Herbert H. F.; Novello, Silvia; Arriola, Edurne; Pérol, Maurice; Goto, Kōichi; Santini, Fernando C.

doi:10.2217/fon-2020-0935

Cited by 35 publications

(33 citation statements)

References 34 publications

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“…In May 2020, the FDA approved selpercatinib for the treatment of metastatic RET-fusion positive NSCLC and metastatic RET-mutant medullary thyroid cancer. Currently underway is the open-label phase 3 trial LIBRETTO-431, comparing the efficacy of selpercatinib to that of standard chemotherapy (cisplatin/carboplatin + pemetrexed) in combination with pembrolizumab in patients with RET-positive NSCLC [ 74 ]. The detailed results of selpercatinib efficacy are presented in the Table 4 .…”

Section: Resultsmentioning

confidence: 99%

Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions

Stencel

Chmielewska

Milanowski

2021

Cancers

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Lung cancer is the most common cause of cancer-related death worldwide, and the prognosis for stage IV remains poor. The presence of genetic alterations in tumor cells, such as EGFR and BRAF gene mutations, as well as ALK and ROS1 gene rearrangements, are indications for targeted therapies. Many such treatments are already registered and used on a wide scale. In comparison to standard chemotherapy, they can prolong not only progression-free survival but also overall survival. Moreover, they are able to provide excellent quality of life and rapid improvement of cancer-related symptoms such as dyspnea, cough and pain. Recent years have witnessed great advances in both molecular diagnostics and new molecular therapies for non-small-cell lung cancer. This review presents new therapeutic targets in NSCLC, as well as drugs of which the activity against NTRK, RET, MET or HER2 gene alterations (including EGFR exon 20 insertions) has either been confirmed or is currently being evaluated. Although these particular genetic alterations in NSCLC are generally rare, each accounting for 1–2% of patients, in total about half of all patients have molecular alterations and may ultimately receive targeted therapies.

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Section: Resultsmentioning

confidence: 99%

Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions

Stencel

Chmielewska

Milanowski

2021

Cancers

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“…For the first question, there are currently two ongoing phase III clinical trials that are comparing selpercatinib or pralsetinib to platinum-based chemotherapy with or without pembrolizumab as an initial treatment for advanced or metastatic RET+ NSCLC patients (Table 3). The LIBRETTO-431 trial is a phase III trial involving metastatic or stage IIIB-C naive patients not suitable for radical surgery or radiation therapy [49]; patients must have a RET gene fusion found from a tumour biopsy or in blood samples. In this trial, patients will be randomised to receive selpercatinib or pemetrexed plus carboplatin or cisplatin with or without pembrolizumab.…”

Section: Discussionmentioning

confidence: 99%

RET Inhibitors in Non-Small-Cell Lung Cancer

Cascetta

Sforza

Manzo

et al. 2021

Cancers

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RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

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“…The sponsor has initiated a phase III trial (LIBRETTO-431) to assess the efficacy and safety of selpercatinib against active comparators currently used in clinical practice in the treatment-naive population (NCT04194944). 29 The clinical experts consulted by CADTH noted that there is limited evidence that patients with metastatic RET fusion-positive NSCLC benefit from currently available single-drug immunotherapy in practice, and not all patients respond to chemotherapy plus immunotherapy, indicating an unmet need for this patient population.…”

Section: Internal Validitymentioning

confidence: 99%

Selpercatinib (Retevmo)

CADTH¹

2022

cjht

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CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses selpercatinib (Retevmo), 40 mg and 80 mg, capsules, oral. Indication: As monotherapy for the treatment of metastatic RET fusion–positive non–small cell lung cancer in adult patients.

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Phase III Study of Selpercatinib Versus Chemotherapy ± pembrolizumab in Untreated RET Positive Non-Small-Cell Lung Cancer

Cited by 35 publications

References 34 publications

Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions

Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions

RET Inhibitors in Non-Small-Cell Lung Cancer

Selpercatinib (Retevmo)

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