Comprehensive analysis of treatment modes and clinical outcomes of small cell lung cancer transformed from epidermal growth factor receptor mutant lung adenocarcinoma

Abstract

Background Transformation to small cell lung cancer (SCLC) is a resistance mechanism of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) patients treated with EGFR tyrosine kinase inhibitors (TKIs). Here, we describe the clinical characteristics and prognosis of these patients and explore the treatment modes after transformation. Methods EGFR‐mutant LADC patients with SCLC transformation were retrospectively included in the study. Demographic and clinical data were collected. Survival outcomes and corresponding influential factors were analyzed. Results Twenty‐nine patients were included in the study. The median progression‐free survival (PFS) of patients who received first‐line EGFR‐TKIs was 13.1 months. The median time to SCLC transformation was 27.5 months. After transformation, the objective response rates of patients who received first‐line chemotherapy with or without EGFR‐TKIs were 43.8% and 37.5%, respectively. The median PFS of patients reveiving chemotherapy with EGFR‐TKIs was significantly longer than that of patients receiving chemotherapy without EGFR‐TKIs (5.2 vs. 3.0 months; HR, 0.19; 95% CI: 0.05–0.72; p = 0.014). However, there was no significant difference in median overall survival (OS) between patients who received chemotherapy with or without EGFR‐TKIs (14.8 vs. 13.0 months; p = 0.474). In the multivariate Cox proportional hazards regression analysis, both anti‐angiogenic treatment (HR, 0.04; 95% CI: 0.01–0.29; p = 0.001) and local radiotherapy (HR, 0.28; 95% CI: 0.08–0.97; p = 0.044) were significantly associated with better patient OS after transformation. Conclusions Compared with chemotherapy alone, the combination of chemotherapy and EGFR‐TKIs as first‐line treatment after SCLC transformation can benefit patients in PFS but not in OS. However, anti‐angiogenic therapies and local radiotherapy can significantly prolong OS after transformation.

Histologic transformation in lung cancer: when one door shuts, another opens

“…An OS of 9–15 months from the time of HT diagnosis has been reported in previous literature. 10 , 119 – 121 Moreover, the OS and PFS of HTs to SCLC were comparable with those of de novo SCLC. 122 , 123 From the perspective of disease behavior, one previous report suggested that HT to SCLC in patients with EGFR mutation-positive NSCLC might be more aggressive than in patients without EGFR -mutation because the median time to HT for patients with EGFR -mutation was significantly shorter than that for patients without EGFR -mutation.…”

“…In a retrospective study, the PFS after HTs of patients receiving chemotherapy with EGFR-TKIs was significantly longer than that of patients receiving chemotherapy without EGFR-TKIs (5.2 versus 3.0 months, p = 0.0014). 121 However, the OS benefit has not been demonstrated; thus, the efficacy of continuing TKI therapy has not reached consensus. Another study has implied the beneficial efficacy of multi-kinase inhibitor therapy after HTs in patients with lung cancer.…”

ALK-Positive Adenocarcinoma After Acquired Resistance to Lorlatinib and Transformation to SCLC: A Case Report

“…Although there was little benefit observed for this patient, research has revealed that patients with transformed SCLC treated with anlotinib have significantly prolonged overall survival compared with those who did not receive anlotinib treatment. 12 …”

Heterogeneity or transformation? A whack‐a‐mole case of EGFR‐mutant lung adenocarcinoma and small cell carcinoma: A case report

“…Continuous osimertinib possibly contributed to survival over 1 year after LM diagnosis. Additionally, although no significant survival benefit was obtained, combination therapy with cytotoxic chemotherapy and EGFR‐TKI could improve response rate and progression free survival after transformation from EGFR ‐mutated adenocarcinoma to SCLC 9 . To maximize patients' benefit, combination therapy could be one of treatment options, especially those with LM 10 …”