Clinical course of EGFR-mutant NSCLC transforming to SCLC documented
medwireNews: Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) that transforms to small-cell lung cancer (SCLC) is characterized by a high rate of TP53 mutation and a lack of response to immunotherapy, among other features, show researchers.
Lecia Sequist (Massachusetts General Hospital, Boston, USA) and colleagues say that “little is known about the clinical course of patients with EGFR-mutant cancer after SCLC transformation, which leads to uncertainty about appropriate treatments and prognostic implications for clinicians.”
To address this, they performed a retrospective chart review of 67 patients (median age 56 years, 57% women) with EGFR-mutant SCLC or high-grade neuroendocrine carcinoma.
At the time of initial lung cancer diagnosis, 87% of the patients had NSCLC histology, predominantly adenocarcinoma, and 13% had de novo SCLC or mixed histology including SCLC.
All of the patients carried EGFR mutations, most commonly exon 19 deletion (69%) or L858R (25%) and all 58 patients with NSCLC at diagnosis received at least one EGFR tyrosine kinase inhibitor prior to SCLC transformation.
Transformation to SCLC occurred at a median 17.8 months after metastatic lung cancer diagnosis but was seen as early as 2 months and as late as 5 years after, the researchers report in the Journal of Clinical Oncology.
Following SCLC transformation, platinum–etoposide was the most commonly used regimen, given to 82% of patients, and yielded a clinical response rate of 54%. In addition, one-third (32%) of patients were treated with a taxane-containing regimen and 50% responded to such treatment.
Sequist and team say that this response rate is “noteworthy” because the response to taxane therapy in classic SCLC is typically around 20–30%.
“It is possible that taxanes are more active in EGFR-mutant transformed SCLC because of residual NSCLC clones that also are responding well to a taxane,” they write, adding that prospective studies of taxanes “should be considered for this population.”
Also noteworthy, according to the investigators, was the complete lack of response observed among 17 patients who received an immune checkpoint inhibitor.
The team says that this reflects “the poor activity of immunotherapy in more classic EGFR-mutant adenocarcinoma” and “suggests that these tumors are biologically more akin to the parental EGFR-mutant adenocarcinoma than to smoking-associated classic SCLC cases.”
The most common mutations detected following transformation to SCLC were TP53 (79% of 48 patients), Rb1 (58% of 31 patients), and PIK3CA (27% of 52 patients).
The investigators also note that all 59 patients with genotyping data at transformation retained their founder EGFR mutation, but 15 of the 19 individuals who were previously positive for EGFR T790M were T790 wild-type at transformation.
Median overall survival after transformation SCLC was 10.9 months and 64% of patients developed central nervous system metastases during this time.
Sequist et al conclude: “Additional investigation and ongoing multicenter collaborations are needed to better elucidate optimal strategies for this group.”
By Laura Cowen
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