Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Subbiah, Vivek; Paz‐Ares, Luis; Besse, Benjamin; Moreno, Víctor; Peters, Solange; Sala, María; López-Vilariño, José Antonio; Fernández, Cristian; Kahatt, Carmen; Alfaro, Vicente; Siguero, Mariano; Zeaiter, Ali; Zaman, Khalil; López, Rafael; Ponce, Santiago; Boni, Valentina; Arrondeau, Jennifer; Delord, Jean‐Pierre; Martínez, Maite; Wannesson, Luciano; Antón, Antonio; Valdivia, Javier; Awada, Ahmad; Kristeleit, Rebecca; Olmedo, María Eugenia; Rubio, María Jesús; Sarantopoulos, John; Chawla, Sant P.; Mosquera-Martínez, Joaquín; Arcangelo, Manolo D’; Santoro, Armando; Villalobos, Víctor M.; Trigo, José

doi:10.1016/j.lungcan.2020.10.003

Cited by 22 publications

(23 citation statements)

References 28 publications

(46 reference statements)

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“…In the subgroup of patients with a CTFI of greater than 180 days ( n = 20), the response rate was 60% with a median OS of 16.2 months. 32 Notably, the majority of patients in this subgroup had limited stage disease at the time of initial diagnosis.…”

Section: Efficacymentioning

confidence: 93%

An overview of lurbinectedin as a new second-line treatment option for small cell lung cancer

Patel

Petty

2021

Ther Adv Med Oncol

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Small cell lung cancer (SCLC) is a highly proliferative, aggressive form of lung cancer that carries a poor prognosis. Recent approvals with new therapeutic options represent the first in more than a decade for SCLC. Lurbinectedin, a newly approved second-line option, is a synthetic alkaloid that covalently binds DNA, generating double-strand breaks, and disrupts DNA-protein interactions and RNA transcription. Lurbinectedin may also modulate the tumor microenvironment by inducing apoptosis of peripheral blood monocytes and tumor associated macrophages, decreasing expression of the inflammatory chemokine (C-C motif) ligand 2 (CCL2) and reducing tumor angiogenesis. A single-arm, open-label, basket trial included 105 patients with SCLC that had received one prior line of therapy. Patients received lurbinectedin 3.2 mg/m2 as an intravenous infusion every 3 weeks, resulting in a response rate of 35.2% and a disease control rate of 68.6%. The response rate was 45% among those with >90 days chemotherapy free interval (CTFI) and 22% in the resistant group (CTFI < 90 days). The median overall survival was 9.3 months. Myelosuppression is the most frequent clinically significant adverse event, particularly neutropenia; however, neutropenic fever occurred in only 5% of those in the SCLC cohort of the basket trial. Nausea and fatigue were also noted. The side effect profile compares favorably to topotecan, while a direct comparison of tolerability can be made between lurbinectedin versus topotecan or pegylated-liposomal doxorubicin from CORAIL, a randomized study for platinum-resistant/refractory ovarian cancer. A press release has reported the ongoing clinical trial for SCLC including combination lurbinectedin and doxorubicin versus topotecan or cyclophosphamide, doxorubicin, and vinblastine to be negative. The details may provide more insight at publication, and future trials will be important to further define the clinical utility of lurbinectedin. Lurbinectedin represents a new option in second-line SCLC.

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Section: Efficacymentioning

confidence: 93%

An overview of lurbinectedin as a new second-line treatment option for small cell lung cancer

Patel

Petty

2021

Ther Adv Med Oncol

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“…160 In a subset analysis of the phase 2 trial previously discussed, lurbinectedin was assessed as second-line therapy in 20 patients with SCLC who had received firstline platinum/etoposide more than 6 months ago. 161 The overall response rate was 60% (95% CI, 36.1%-86.9%).…”

Section: Subsequent Systemic Therapymentioning

confidence: 95%

“…Recommended subsequent systemic therapy options for patients who have relapsed are listed in the algorithm and described here, including the clinical trial data supporting the recommendations (see SCL-E 2, page 1451). [160][161][162][163][164][165] Lurbinectedin Lurbinectedin inhibits oncogenic transcription, leading to tumor cell apoptosis. A phase 2 basket trial assessed lurbinectedin as second-line therapy in 105 patients with SCLC who had received first-line platinum/etoposide; only 8% of patients had received immunotherapy.…”

Section: Subsequent Systemic Therapymentioning

confidence: 99%

Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Ganti

Loo

Bassetti

et al. 2021

Journal of the National Comprehensive Cancer Network

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211

183

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The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

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Section: Clinical Efficacymentioning

confidence: 99%

“…This demonstrates that lurbinectedin may be an option in patients with platinum-sensitive disease and may represent a viable alternative to retreatment with a platinum-based chemotherapy regimen in patients with a chemotherapy-free interval >180 days. 21 Historically in SCLC, topotecan has shown an OR of 16.9% and median OS of 7.8 months, and cyclophosphamide/doxorubicin/vincristine (CAV) has shown an OR of 18.3% and median OS of 5.7 months. 9 In an ongoing phase III trial (ATLANTIS), lurbinectedin/doxorubicin is being compared to topotecan or CAV for relapsed/refractory SCLC patients who have failed 1 previous line of platinumbased chemotherapy.…”

Section: Clinical Efficacymentioning

confidence: 99%

Lurbinectedin: A New Treatment Option for Relapsed/Refractory Small-Cell Lung Cancer

Shinn

Reeves

2020

Ann Pharmacother

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Objective To assess the clinical application of lurbinectedin and its role in the therapy of small-cell lung cancer (SCLC). Data Sources PubMed database and ClincialTrials.gov were utilized to perform a comprehensive literature search from August 2011 to mid-November 2020 with the terms lurbinectedin and PM01183. Study Selection and Data Extraction English-language clinical trials of lurbinectedin were evaluated. Data Synthesis Lurbinectedin, as second-line therapy in SCLC, demonstrated an overall response (OR) rate of 35.2% and median overall survival of 9.3 months. Phase II studies in multiple cancers revealed myelosuppression (>95%), increased liver enzymes (>70%), nausea (up to 80%), vomiting (54%), and fatigue (>50%) as the most common adverse events associated with lurbinectedin. CYP3A4 drug interactions affect lurbinectedin exposure (severe pancytopenia occurred after coadministration with aprepitant), and protein binding can affect its clearance. Patients with cardiac comorbidities were not included in published lurbinectedin trials because of cardiotoxicity associated with trabectedin. Relevance to Patient Care and Clinical Practice Lurbinectedin is an option in SCLC after failure of a platinum-based regimen. Dose adjustments, drug interactions, antiemetic regimen choice, and patient comorbidities are important clinical considerations with lurbinectedin use. Likewise, its place in therapy in the era of immune checkpoint inhibitors requires further exploration. Conclusions With a promising OR compared with other second-line options, lurbinectedin should be considered in patients who have failed first-line therapy. Studies are ongoing with lurbinectedin in combination with other agents in SCLC, and a phase III trial is assessing use in combination with doxorubicin compared with other second-line regimens.

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Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Cited by 22 publications

References 28 publications

An overview of lurbinectedin as a new second-line treatment option for small cell lung cancer

An overview of lurbinectedin as a new second-line treatment option for small cell lung cancer

Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Lurbinectedin: A New Treatment Option for Relapsed/Refractory Small-Cell Lung Cancer

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