*June 2025*
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.
Introduction
Osimertinib is a third-generation tyrosine kinase inhibitor (TKI), which forms an irreversible covalent bond with the cysteine-797 residue in the ATP binding site of EGFR and is a standard of care for the treatment of EGFR-mutant NSCLC.1 After an initial good response, progression on TKIs is universal. Histological transformation (HT) is a mechanism of disease progression in NSCLC especially after treatment with TKI and is challenging to treat.2 HT might be seen more frequently in the future owing to the increasing use of molecular testing and availability of more treatment options leading to longer overall survival. Therefore, it is pertinent to evaluate effective treatment modalities and their safety for the treatment of transformed SCLC (tSCLC). In this case series, we report our experience of using lurbinectedin with osimertinib for the treatment of tSCLC.
Materials and Methods
We identified three patients with EGFR mutation with either de-novo SCLC or tSCLC who received treatment with lurbinectedin plus osimertinib (LO). Clinical and laboratory data was extracted by retrospective chart review. Tumors were staged according to the American Joint Committee on Cancer Guidelines (version 8). Response assessment was done using the Response Evaluation Criteria in Solid Tumors, version 1.1. This study was approved by the Institutional Review Board of the Mayo Clinic (23-009882) and informed consent was waived.
Results
All three patients were diagnosed at an advanced stage and had EGFR Exon 19 deletion (Table 1). One patient reported partial response to the LO (Fig. 1), and it was well-tolerated in all three cases. The dose reduction of Lurbinectedin was required in two cases owing to thrombocytopenia. Read more.
