More is less.

August 14, 2017. It’s been a frustrating summer for esophageal cancer. A few weeks ago we told you about RTOG 0436, which showed no benefit to adding cetuximab to standard chemoradiation for inoperable esophageal cancer. Earlier this year, long term results of the SCOPE-1 trial confirmed similarly disappointing results with cetuximab. To complete the trifecta of negative trials, the MRC OE05 was reported this month in Lancet comparing two neoadjuvant chemotherapy regimens: the standard cisplatin + 5-fluorouracil (CF) versus epirubicin + cisplatin + capecitabine (ECX). ECX proved tough, with significantly fewer patients seeing the regimen through to completion (81% vs 96%). Which may explain why it improved neither survival outcomes nor recurrence patterns. But there are still two important takeaways: First, ECX did improve survival in the subset of patients without PET scans prior to enrollment (possibly translating to more occult metastases). Second, survival of the CF cohort was better than that seen with the same regimen in the earlier OE02 trial (2.0 vs 1.4 years). What does this all mean? More accurate staging may washout the benefit of more aggressive systemic therapy treating occult metastases. Bottom line: this highlights the narrow therapeutic index of systemic treatment for localized esophageal cancer where additional toxicity can quickly negate the small benefits of neoadjvuant therapy.