Headline: The CROSS trial has been challenged.
The Study: Advances in systemic and radiation therapies often happen in parallel, which can make for some interesting tumor board argum..eh hm, discussions. While the Neo-AEGIS trial was designed to help clarify the best (neo)adjuvant treatment paradigm for locally-advanced esophageal adenocarcinoma, abstract reporting of preliminary results is still up for interpretation. Most would agree the pre-op standard has been some iteration of radiation and chemotherapy ever since CROSS demonstrated, circa 2012, a survival benefit when it was added to surgery alone. Too bad it didn’t build off MAGIC that demonstrated, circa 2006, a survival benefit when peri-op ECF chemo was added to surgery alone for distal esophagus and EGJ tumors. In Neo-AEGIS, 377 patients with locally advanced esophageal adeno were randomized to the  CROSS regimen versus  MAGIC (pre-2018) or FLOT (2018 and later) regimens. Most patients had cT3 (84%) and/or cN1 (58%) disease.The primary outcome was overall survival with a superiority design. Here’s where things get interesting. The first futility analysis suggested no significant difference would be seen (aka futility), but the authors already had vacation days planned for ASCO and called an audible to switch to a non-inferiority design. At the second futility analysis, survival looked so similar it was deemed no further recruitment would be needed. So after 60% of preordained events, with 3-year survival rates of 56% and 57%, respectively, the authors declare peri-op chemo non-inferior to pre-op chemoradiation. Ok, survival was similar. But R0 resection rate was 82% for chemo vs 95% for CRT, ypN0 was 44.5% vs 60%, tumor regression grade 1-2 12% vs 42%, pCR rate was 5% vs 16%, and 3% vs <1% had neutropenic sepsis. So while there may be no difference in survival between peri-op chemo and chemoRT, what other clinical benefits may favor one regimen over another?
TBL: More data on toxicity, cost, and quality of life are needed to understand the optimal (neo)adjuvant treatment strategy for esophageal cancer. | Reynolds, ASCO 2021