Transformation of NSCLC to Small Cell Lung Cancer
Posted: Friday, May 10, 2019
Recent retrospective study findings, published in the Journal of Clinical Oncology, provide further evidence that EGFR-mutant non–small cell lung cancers (NSCLCS) can undergo transformation to small cell lung cancer (SCLC). In fact, between 3% and 10% of these NSCLCs may do so, at an average of nearly 18 months after diagnosis and often characterized by certain genetic mutations. Nicolas Marcoux, MD, of the Yale Cancer Center, and colleagues noted that ongoing multicenter collaborations are necessary to clarify how best to treat this group of patients.
The researchers retrospectively identified 67 patients—38 women and 29 men—with EGFR mutations, including exon 19 deletion (69%), L858R (25%), and others (6%). At initial cancer diagnosis, 58 patients had NSCLC and 9 had de novo SCLC or mixed histology. All patients received one or more EGFR tyrosine kinase inhibitors before transformation to SCLC.
The median time to transformation was 17.8 months. The median overall survival after diagnosis was 31.5 months, whereas the median survival after transformation to SCLC was 10.9 months. All patients maintained their founder EGFR mutations, whereas recurrent mutations included TP53, Rb1, and PIK3CA. After transformation to SCLC, both platinum/etoposide and taxanes yielded high response rates, but none of the 17 patients who underwent immunotherapy experienced a response. Of the patients, 59 had tissue genotyping at first evidence of SCLC.
“EGFR-mutant lung cancers that transform to SCLC or that have high-grade neuroendocrine histology at the time of diagnosis exhibit high response rates to platinum etoposide, which should be considered the first-line therapy of choice, and also exhibit high response rates to taxanes,” the investigators indicated. “Conversely, these tumors do not respond well to checkpoint inhibitors, and the use of these therapies outside of a clinical trial should currently be discouraged.”
Disclosure: The study authors’ disclosure information may be found at ascopubs.org.