Irinote-can’t.

Top Line: Are irinotecan and cisplatin (IP) more effective than etoposide and cisplatin (EP) for resected high-grade neuroendocrine cancers (HGNEC) of the lung?

The Study: You may remember from last week the Chinese trial that added irinotecan to standard chemoradiation for rectal cancer. Irinotecan toxicity can be tough for many patients, so eligibility was limited to those with genotypes associated with better tolerance of irinotecan. You might also remember that such genotypes are more prevalent in Asian versus western populations. Now, hold that thought. HGNEC of the lung consists of small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). For patients fortunate enough to present with early stage disease, adjuvant systemic therapy--specifically etoposide and cisplatin (EP)--is recommended. For extensive stage SCLC, a phase 3 Japanese trial suggested improved outcomes with IP over EP, but the same wasn’t true for multiple western trials. In this Japanese Japanese trial, 221 patients with resected HGNEC were randomized to adjuvant EP or IP (no radiation). Roughly ⅓ of patients had SCLC, LCNEC, or combined SCLC/LCNEC, respectively. The trial was terminated early for futility because, at 3 years, there was no difference in recurrence-free survival between EP (65%) and IP (69%). EP had significantly higher grade 3+ toxicity, however most of that was hematologic. IP, on the other hand, caused more anorexia, diarrhea, fatigue, and dehydration which was less well tolerated and led to significantly fewer patients in the IP arm completing planned therapy.

TBL: IP is not superior to EP among patients with resected HGNEC as IP toxicity was less tolerable and fewer patients completed planned therapy. | Kenmotsu, J Clin Oncol 2020