Abstract 165P
Background
Small cell lung cancer (SCLC) subtypes are driven by dominant transcriptional programs. Preclinical work suggests that transcriptomic subtyping (ASCL1, NEUROD1, POU2F3 and Inflamed) could inform potential tumor vulnerabilities and support therapeutic decisions. Here we explore the association of SCLC subtypes with clinicopathological and EMT characteristics.
Methods
We performed IHC for ASCL1, NEUROD1, POU2F3, E-cadherin and Vimentin in 42 SCLC samples from a phase IIIB clinical trial of durvalumab+platinum-etoposide as first-line treatment of patients with extensive-stage SCLC (CANTABRICO). IHC evaluation was performed using H-score. Cases expressing more than one marker were classified based on the predominant marker with the higher H-score. We evaluated associations between IHC markers and other clinicopathological and outcome variables with GraphPad®.
Results
Forty-two cases were evaluated, 20 classifieds as ASCL1 (47.6%), 11 as NEUROD1 (26.2%), 4 as POU2F3 (9.5%), and 7 as non-A/N/P (16.7%). Of note, consecutive staining of ASCL1, NEUROD1 and POU2F3 revealed that concomitant expression of these markers was observed in the same tumor in non-overlapping areas. The majority (85.4%) of tumors expressed E-cadherin and 45.2% vimentin. ASCL1 expression in tumor cells was positively correlated with tumoral E-cadherin expression (rho = 0.47, p = 0.0022). No correlation between subtypes and vimentin expression was observed. Baseline lactate dehydrogenase (LDH) was higher in the POU2F3-positive tumors (median = 541 range (379–1102)) compared with the other subtypes (p < 0.0001). Patients with non-A/N/P tumors had no liver or brain metastasis (p < 0.0001). With a median follow-up of 12.4 months, median OS was 8.95 months. Notably, 5 out of 7 patients with non-A/N/P tumors are still alive (p < 0.0001).
Conclusions
Clinical and biological differences are observed among different molecular subgroups in SCLC. In our study, the non-A/N/P tumors (encompassing the inflamed subtype) showed favorable prognostic features and better outcomes with chemoimmunotherapy.
Clinical trial identification
NCT04712903.
Legal entity responsible for the study
The authors.
Funding
AstraZeneca.
Disclosure
L. Baez: Other, Personal and Institutional, Other, Working: AstraZeneca. Á. Callejo Mellén: Other, Personal and Institutional, Other, Working: AstraZeneca. All other authors have declared no conflicts of interest.