Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer: A case report

Abstract

BackgroundHistological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of mechanisms of the acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). However, SCLC transformation and tumor heterogeneity have never been reported in sequential targeted therapy and immunotherapy.Case presentationHere, we described a patient with advanced EGFR-mutant NSCLC, who received erlotinib and underwent the resistance with EGFR T790M (–). The patient then received chemotherapy plus immunotherapy of programmed cell death 1 (PD-1) inhibitor, encountered progression with pathological transformation from NSCLC to SCLC that was overcome by chemotherapy of etoposide plus carboplatin (EC) with the main lesion significantly shrinking while metastatic nodules increasing. The pathology of the metastatic nodule showed NSCLC with EGFR T790M (+). Based on the tumor heterogeneity, EC chemotherapy combined with osimertinib was used, and patients responded well. The patient experienced four lung biopsies in all, which helped to provide the patient with precise treatment.ConclusionsThis case suggested that SCLC transformation and tumor heterogeneity should be paid attention to when disease progression occurred in advanced NSCLC whether receiving targeted therapy or immunotherapy.

Transformation of epidermal growth factor receptor mutated lung adenocarcinoma to small-cell carcinoma long after the cessation of tyrosine kinase inhibitor treatment: A case series and literature review

“…In other studies, Ferrer et al and Wang et al demonstrated that 39 of 48 patients (81 %) and 22 of 25 patients (88 %) were receiving EGFR-TKIs at the time of transformation [ 7 , 10 ], suggesting that some patients with EGFR -mutated NSCLC show SCLC transformation after the cessation of EGFR-TKIs. Therefore, we performed a literature review [ 3 , 9 , [11] , [12] , [13] , [14] , [15] ] and summarized these cases ( Table 1 ). In most of these reports, SCLC transformation was observed within two to seven months of cessation of TKI administration.…”

“…19 del erlotinib (more than 2 years) NA a 2 van Riel S et al [ 13 ] 42 F NA a erlotinib (10 months) CBDCA + PTX, erlotinib, DTX 2 Zakowski MF et al [ 9 ] 45 F NA a erlotinib (18 months) mitomycin + vinblastine 2 Morinaga R et al [ 12 ] 46 F Ex. 19 del gefitinib (10 months) NA a 5 Yang MH et al [ 15 ] 50 M Ex. 19 del erlotinib (6.5 months) CBDCA + PTX + toripalimab 6.6 Popat S et al [ 11 ] 46 F Ex.…”

Transformation of Lung Squamous Cell Carcinoma to Small Cell Lung Cancer After Immunotherapy Resistance: A Case Report

“…8 Several studies have shown that small cell transformation is commonly recognized as one of the resistance mechanisms to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant NSCLC, which accounts for 3-14% of resistant cases. [9][10][11] In addition, small cell transformation in advanced NSCLC patients treated with EGFR-TKIs is associated with poor survival outcomes. 12 Recently, small cell transformation is extremely rare for advanced NSCLC patients who have failed immunotherapy.…”