Adjuvant chemotherapy intensity and prognosis in completely resected high-grade neuroendocrine lung carcinoma: a post hoc analysis of JCOG1205/1206

INTRODUCTION: We aimed to clarify the prognostic impact of adjuvant chemotherapy intensity in patients with high-grade neuroendocrine carcinoma (HGNEC) of the lung using a post hoc analysis of the phase III JCOG1205/1206 trial comparing irinotecan plus cisplatin (IP) with etoposide plus cisplatin (EP). MATERIAL AND METHODS: We included 217 patients (109 and 108 received EP and IP, respectively) with p-stage I-IIIA HGNEC. Prognosis was assessed based on treatment completion (four cycles) and relative dose intensity (RDI) of adjuvant chemotherapy, calculated for each regimen and agent, using Cox proportional hazards models. RESULTS: Median regimen RDI was similar (87.2% vs. 89.6%), whereas treatment completion rate was higher in EP (89.0% vs. 74.1%; P = 0.0046). Five-year relapse-free survival (RFS) among patients who completed versus did not complete treatment was 66.0% versus 73.3% in EP arm (hazard ratio [HR], 1.944; 95% CI, 0.590-6.404) and 67.4% versus 64.1% in IP arm (HR, 0.874; 95% CI, 0.437-1.745). RDI ≥90% was associated with worse RFS in EP arm (HR, 2.024; 95% CI, 1.081-3.787) but not in IP arm (HR, 1.123; 95% CI, 0.608-2.072). In EP arm, cisplatin and etoposide RDI ≥90% were associated with worse RFS (HR, 1.926; 95% CI, 1.029-3.605 and HR, 2.024; 95% CI, 1.081-3.787, respectively), whereas no significant associations were observed for cisplatin or irinotecan in the IP arm. CONCLUSION: In completely resected HGNEC, high-intensity adjuvant chemotherapy was not clearly associated with improved prognosis. Higher RDI in the EP regimen was associated with poorer RFS, suggesting that the pursuit of high RDI may not be necessary in adjuvant HGNEC treatment.