Transformation to small cell lung cancer after first-line afatinib treatment

Abstract

Acquiring resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is inevitable. Transformation to small cell lung cancer (SCLC) is reported as a possible mechanism of this acquired resistance. We describe the case of a 35-year-old man with lung adenocarcinoma harboring EGFR exon 19 deletion. After 7 months of successful treatment with afatinib, he experienced relapse and rebiopsy revealed SCLC with EGFR exon 19 deletion. Tumor marker tests at this point showed normal levels of serum neuron-specific enolase and pro-gastrin releasing peptide. Our case highlights the importance of rebiopsy for revealing SCLC transformation, a potential mechanism of acquired resistance to afatinib as with other EGFR-TKIs, and normal-range values of tumor markers for SCLC cannot exclude the possibility of SCLC transformation.

Transformation of ALK expression and PD-L1 0% to PD-L1 90% only after surgery: the need for rebiopsy in lung cancer patients

“…Chemotherapy might transform a SCLC to adenocarcinoma with T790M expression, but also, osimertinib might transform an adenocarcinoma with T790M expression to SCLC 15,17. There are also cases where afatinib administration transformed adenocarcinoma to SCLC18 and both SCLC and squamous cell carcinoma 19. Moreover, it has been observed that ALK-positive patients might transform to SCLC 20.…”

Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies

“…Lastly, transformation of NSCLC into SCLC is hypothesized as a possible mechanism of acquired resistance to EGFR-TKIs [11,50]. After SCLC transformation, the EGFR mutation is retained, EGFR protein decreases, and patients show limited response to EGFR-TKIs [51].…”

Understanding the Mechanisms of Resistance in EGFR-Positive NSCLC: From Tissue to Liquid Biopsy to Guide Treatment Strategy

“…The first report described a case of a lung adenocarcinoma harboring EGFR exon 19 deletion that, after seven months of treatment with afatinib, progressed and showed SCLC transformation at re-biopsy with concomitant EGFR exon 19 deletion. Afatinib was discontinued and chemotherapy was administered with a cisplatin and irinotecan regimen, with no disease progression after four cycles of chemotherapy [95]. Similarly, the second case report described a switch of tumor histotype to SCLC with features of a G3 neuroendocrine carcinoma and positivity for exon 19 deletion of EGFR .…”