Small cell lung cancer differentiation in patients with driver mutant non-small cell lung cancer: a single center experience.

Introduction: In the treatment of metastatic non-small cell lung cancer (mNSCLC), targeted therapies are utilized in the presence of driver mutations. Tyrosine kinase inhibitors (TKIs) have contributed positively to survival outcomes in this patient group. In driver mutant mNSCLC patients, caution is warranted for the development of small cell lung cancer (SCLC) differentiation following progression under TKI therapy. SCLC is associated with an aggressive course and shorter survival. The cornerstone of SCLC treatment is conventional chemotherapy. In this study, we aimed to present the development of SCLC differentiation in driver mutant mNSCLC patients who received at least one line of TKI therapy as a single-center experience.

Patients and methods: Between April 2013 and January 2024, the medical records of 144 patients diagnosed with mNSCLC and found to harbor driver mutations were retrospectively reviewed at Necmettin Erbakan University Faculty of Medicine Hospital, Oncology Clinic. All patients had received at least one line of TKI. The analysis included evaluation of driver mutations, treatments administered, and the rate of SCLC differentiation in this patient population.

Results: A total of 144 patients were included in the study. Among them, 122 patients (84.9%) had an EGFR mutation, 21 patients (15.1%) had an ALK mutation, and 1 patient had a ROS1 mutation. TKI therapy was administered as first-line treatment in 50% of the patients, as second-line in 40.3%, and as third-line in 6.3%. Biopsies were performed in 22 out of 144 patients after disease progression. Of these, 21 biopsies were from patients with EGFR mutations, and 1 was from a patient with an ALK mutation. Biopsies were conducted after first-line therapy in 8 cases, after second-line therapy in 11 cases, and after third-line therapy in 3 cases. SCLC differentiation was observed in 3 out of 22 patients (13.6%), all of whom had EGFR mutations. Additionally, 2 of these 3 patients developed SCLC differentiation following first-line TKI therapy, while 1 developed it after second-line TKI therapy.

Discussion: The rate of SCLC differentiation in NSCLC is generally low and is considered rare. It is estimated that the rate of SCLC differentiation in NSCLC ranges between 1% and 3%. In our clinic, when evaluating driver mutant mNSCLC patients who received at least one line of TKI therapy, SCLC differentiation was observed in 3 patients (13.6%). The limitations of our study include its retrospective nature and the small sample size. However, the findings suggest that SCLC differentiation is a potential occurrence in driver mutant mNSCLC patients treated with TKIs. Therefore, careful monitoring and the detection of possible differentiation are essential in the follow-up of these patients.