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. 2025 Feb 13;6(6):100807.
doi: 10.1016/j.jtocrr.2025.100807. eCollection 2025 Jun.

Combination of Lurbinectedin and Osimertinib for Treatment of EGFR-Mutated Transformed SCLC: A Brief Report

Aditi Singh  1 , Arthi Sridhar  1 , Aastha Poddar  2 , Anastasios Dimou  1 , Kaushal Parikh  1 , Mohamed Shanshal  1 , Anna Schwecke  1 , Nicole Moffett  1 , Manish R Patel  3 , Aaron S Mansfield  1 , Konstantinos Leventakos  1
Affiliations

Combination of Lurbinectedin and Osimertinib for Treatment of EGFR-Mutated Transformed SCLC: A Brief Report

Aditi Singh et al. JTO Clin Res Rep. .

Abstract

Third-generation tyrosine kinase inhibitors are effective treatment of EGFR-mutated NSCLC. After an initial response, patients on this therapy ultimately develop resistance leading to disease progression. One of the resistance mechanisms is histological transformation to SCLC. There is no standard of care for the management of transformed SCLC. Given the rarity of transformed SCLC, it is important to study treatment options that are safe and effective for this disease. In this case series, three patients received treatment with lurbinectedin plus osimertinib after transformation to SCLC. In our limited experience, the combination was found to be safe.

Keywords: Drug resistance; EGFR; Lurbinectedin; NSCLC; Osimertinib; SCLC; Tranformed SCLC.

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Conflict of interest statement

Dr. Dimou reports grants from the 10.13039/100000005Department of Defense, 10.13039/100011913A Breath of Hope, The Mathy Family Development fund; support for attending meetings and/or travel from IASLC, honoraria from MultiMedia Medical LLC; consulting fees from TP Therapeutics, Guardant Health, Chromacode, AnHeart Therapeutics, and Rigel Pharmaceuticals. Dr. Parikh reports consulting fees from 10.13039/100011096Jazz Pharmaceuticals, Guardant Health, Regeneron, Rigel Pharmaceuticals, AstraZeneca; honoraria from MJH Life Sciences, Dava Oncology Intellisphere, Clinical Education Alliance; support for attending meetings and/or travel from DAVA Oncology. Ms. Schwecke reports royalties or licenses from InveniQA, honoraria from APPOS, and UMOEN; and participation on a data safety monitoring board or advisory board for the Mayo Clinic. Ms. Moffett reports honoraria from APPOS. Dr. Patel reports grants from AstraZeneca. Dr. Mansfield reports grants from Novartis, Verily; consulting fees from Rising Tide, TRIPTYCH Health Partners—expert think tank; honoraria from Janssen, BeiGene, Chugai Pharmaceutical Co Ltd (Roche), Ideology Health LLC (formerly Health Media), AXIS Medical Education Inc, Johnson &amp, Johnson Global Services, Intellisphere LLC, Answers in CME, Ideology Health (formerly Nexus Health Media); participation on a data safety monitoring board or advisory board for Abbvie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Janssen, Takeda, Sanofi Genzyme, Gilead, support for attending meetings and/or travel Shanghai Roche; leadership or fiduciary role with mesothelioma applied research foundation, friends of Patan hospital; and other financial or non-financial roles in Genentech, Janssen, Johnson & Johnson Global Services, Bristol Meyers Squibb. Dr. Leventakos reports grants from AstraZeneca, Mirati Therapeutics; consulting fees from Amgen, Boehringer Ingelheim Pharmaceuticals, Daiichi Sankyo, Janssen Biotech, Novartis; honoraria from MJH Life Sciences, AstraZeneca Interdisciplinary Corporation, OncLive State of the Summit, MD Outlook, Targeted Oncology; participation on a data safety monitoring board or advisory board for AstraZeneca, Jazz Pharmaceuticals, Mirati Therapeutics, Regeneron, Targeted Oncology, Janssen, and Takeda. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Response to LO. LO, lurbinectedin plus osimertinib. Figure 1.1. (A–C) PET-CT scan showing disease progression after carboplatin/etoposide/atezolizumab with increasing metabolic activity of thoracic lymph nodes, adrenal gland lesions, and lesion in the left hepatic lobe with development of additional lesions in the right hepatic lobe, lesion in the pancreatic body/tail, and innumerable additional osseous lesion. (D–F) Significant improvement in the progressive disease after two cycles of LO. LO, lurbinectedin plus osimertinib; PET-CT, positron emission tomography–computed tomography. Figure 1.2. (A–C) A CT scan shows disease progression after carboplatin/etoposide/atezolizumab with new pulmonary nodules and a mass centered in the right abdominal wall indenting the right lobe of the liver. (C–F) A CT scan shows improvement in peri-hepatic metastatic disease but a progression of metastatic disease in the thorax. CT, computed tomography. Figure 1.3. (A–C) PET-CT scan shows progressive disease on carboplatin/etoposide/atezolizumab with osseous and pulmonary lesions. (D–F) Shows disease progression on LO with worsening osseous and pulmonary lesions. LO, lurbinectedin plus osimertinib; PET-CT, positron emission tomography–computed tomography.
Figure 2
Figure 2
Treatment timeline. SBRT, stereotactic body radiation therapy.
See this image and copyright information in PMC

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