Relationship between patterns of immunohistochemical conventional neuroendocrine markers and efficacy of immune check point inhibitors in patients with extensive disease small cell lung cancer

BackgroundWhich patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)-SCLC, to assess whether conventional NE markers are predictive of ICIs.MethodsPatients with untreated ED-SCLC who received first-line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first-line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI-chemo group) and with chemotherapy alone (chemo group).ResultsA total of 227 patients were included in the ICI-chemo and chemo groups, respectively. The progression-free survival (PFS) tended to be better in patients in the ICI-chemo group than those treated with chemotherapy alone in patients with NE marker-positive SCLC. In particular, it was statistically significant in patients with chromogranin A-positive SCLC (p = 0.036). In patients with NE marker-negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker.ConclusionOur study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker-negative SCLC. We retrospectively analyzed the relationship between the efficacy of ICIs and the expression patterns of conventional NE markers in ED-SCLC. PFS tended to be better in the ICI-chemo group than in the chemo-group in any NE marker-positive SCLC. However, no significant differences were observed in any of the NE marker-negative SCLC patients between the groups. Our study suggests that the efficacy of ICIs in addition to chemotherapy may not be demonstrated in conventional NE marker-negative SCLC.image