Study finds Regimen that doesn’t include Radiation is Better than current Standard

The FLOT protocol includes chemotherapy (fluorouracil, leucovorin, oxaliplatin, docetaxel) before and after surgery. The CROSS protocol includes neoadjuvant chemotherapy (paclitaxel/carboplatin) plus radiation (41.4 Gy) followed by surgery.

In the new trial, funded by the German Research Foundation, 438 people with locally advanced esophageal cancer were randomly assigned to receive either perioperative chemotherapy with the FLOT regimen or neoadjuvant chemoradiation with the CROSS regimen.

After completing treatment, 35 of the 191 patients in the FLOT group had complete disappearance of their tumor, known as a complete response, compared with 24 of the 180 patients in the CROSS group.

Patients who received the FLOT regimen lived a median of 5 years and 6 months, compared with about 3 years for patients in the CROSS group. Three years after completion of treatment, 57% of people in the FLOT group and 51% of patients in the CROSS group were still alive.

The rate of complications after surgery was similar among both groups. However, within 90 days of surgery, about 3% of participants in the FLOT group had died, compared with nearly 6% of participants in the CROSS group.

“The study will have an impact on national and international treatment guidelines for esophageal cancer. Currently, both examined protocols are recommended by the guidelines…and considered equivalent concerning improvement of long-term survival,” remarked Jens Hoeppner, MD, of the University Medical Center OWL in Detmold, Germany, who presented the ESOPEC results. “The ESOPEC study is estimated to change this assumption and thereby change practice on the international level.”

Karyn A. Goodman, M.D., of the Icahn School of Medicine at Mount Sinai in New York believes that the FLOT regimen should now be the standard of care for most people with locally advanced esophageal cancer.  But she believes with the rise of immunotherapies, that may change.

For example, a trial called CheckMate 577 showed that giving the immunotherapy drug nivolumab (Opdivo) after the CROSS regimen and surgery may be an effective option. In that trial, which included people considered to be at high risk of their cancer coming back, giving nivolumab after surgery improved how long participants lived without their disease returning.

So particularly in combination with nivolumab, CROSS may have some advantages for certain patients, Dr. Goodman pointed out.

For example, people with esophageal cancer tend to be elderly and have other health problems, she explained. “The CROSS regimen is … very well tolerated by these patients. And I think … the CROSS regimen, followed by adjuvant nivolumab, is still a potential option for many of these patients,” Dr. Goodman said.