De Novo KRAS G12C-Mutant SCLC: A Case Report

Abstract

The application of KRAS G12C inhibitors in the setting of NSCLC represents a major milestone for a previously "undruggable" target. Here, we present the second reported case of de novo KRAS G12C-mutant primary SCLC. Would our patient benefit from a KRAS G12C inhibitor?

Keywords: Case report; KRAS G12C; Small cell lung cancer; Targeted therapy.

Figure 1

The patient’s clinical course with radiographic and ctDNA monitoring. The patient’s clinical course until the most recent follow-up is illustrated. The colored bars represent active treatment periods (light green = SRS; blue = carboplatin, etoposide, atezolizumab; dark green = concurrent chemoradiation with carboplatin and etoposide; purple = maintenance atezolizumab). The red dots indicate blood collection time points. Direct smear and cell block (illustrated) H&E stain detailing cytologic features typical of small cell carcinoma. (B) The molecular genetic testing results with specific alterations detected in initial biopsy specimen are represented. The relative frequency reported in seminal publications by Rudin et al. (left) and George et al. (right) of each mutation are shown. (C) Percentage mutant allele frequencies of all pathogenic variants detected in ctDNA are shown. Variants of unknown significance identified in ctDNA include RB1 E629D, PTCH1 I374V, and NTRK1 H291P. Colored boxes indicate treatment periods as above. Pathogenic TP53 variants have been detected only at low allele frequencies, possibly representing CHIP. No KRAS G12C has been detected in ctDNA to-date. Carbo, carboplatin; ChemoRT, chemoradiotherapy; CHIP, clonal hematopoiesis of indeterminate potential; CT, computed tomography; ctDNA, circulating tumor DNA; etop, etoposide; H&E, hematoxylin and eosin; MRI, magnetic resonance imaging; SRS, stereotactic radiosurgery; VAF, variant allele frequency.