Perioperative Chemo Shows Longer Survival in Esophageal Cancer

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Perioperative chemotherapy with chemotherapy led to improved survival outcomes versus neoadjuvant chemoradiation in resectable esophageal cancer.

Perioperative chemotherapy (treatment around the time of surgery) with chemotherapies demonstrated survival benefits, compared with neoadjuvant (presurgical) chemoradiation in patients with surgically removable locally advanced esophageal cancer, according to a phase 3 trial.

Findings from the phase 3 ESOPEC trial were shared via a news release during the 2024 ASCO Annual Meeting.

Study Highlights:

  • This study compared two treatment approaches for patients with locally advanced, surgically removable esophageal cancer. One approach is perioperative chemotherapy, which involves giving chemotherapy drugs before and after surgery. The other approach is neoadjuvant chemoradiation, which involves giving chemotherapy drugs along with radiation therapy before surgery.
  • The study found that perioperative chemotherapy led to a longer overall survival rate than neoadjuvant chemoradiation. The median overall survival was 66 months for patients who received perioperative chemotherapy compared to 37 months for patients who received neoadjuvant chemoradiation.
  • Perioperative chemotherapy involved giving four chemotherapy drugs: 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT). These drugs were given every two weeks for four cycles before surgery and four cycles after surgery.

ESOPEC was a study that involved patients with esophageal adenocarcinoma in Germany. Eligible patients needed to be at least 18 years old, have received no prior abdominal or thoracic radiotherapy, have an ECOG performance status of 2 or less (could perform daily tasks independently) and have adequate organ function.

The primary end point (main result measured at the end of the study) was overall survival (OS; living with cancer, regardless of disease status). Secondary end points included progression-free survival (time without the cancer worsening or spreading), recurrence-free survival (living without the cancer returning) and quality of life following surgery.

Patients were randomly assigned evenly into two groups to receive either perioperative chemotherapy or neoadjuvant chemoradiation. The median ages of patients in the study were 63.1 years old and 62.6 years old in the perioperative chemotherapy group and the neoadjuvant chemoradiation group, respectively. Researchers reported that most patients in both groups identified as male (89.1% versus 89.4%, respectively).

Overall, 191 patients in the perioperative chemotherapy group underwent surgery compared with 180 patients in the neoadjuvant chemoradiation group.

Patients in the perioperative chemotherapy group received repeated doses of four types of chemotherapies: 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT).

In the neoadjuvant chemoradiation group, patients received neoadjuvant radiation therapy and concurrent chemotherapy with carboplatin and paclitaxel five weeks prior to surgery.

At a median follow-up of 55 months, 221 patients who received perioperative chemotherapy achieved a median OS of 66 months compared with 37 months among 217 patients who were treated with the neoadjuvant chemoradiation.

The three-year OS rates were 57% versus 51%, respectively. Among 359 patients whose tumor regression status (how much the tumor has shrunk) was known, 35 patients in the perioperative chemotherapy group experienced a pathological complete response (tumor disappearance) versus 24 patients in the neoadjuvant chemoradiation group.

“Many patients in the US and Europe are still treated with the radiochemotherapy protocol. Our study shows that patients with resectable esophageal cancer should have FLOT chemotherapy before and after the operation in order to optimize the chance of curing their tumors in the long term,” Dr. Jens Hoeppner, the director of the Department of Surgery at University Medical Center, University of Bielefeld, in Detmold, Germany, stated in a press release.

In the 90 days post-surgery, 3.2% of patients in the perioperative chemotherapy group died compared with 5.6% in the neoadjuvant chemoradiation group. The 30-day postoperative mortality rates were 1.0% versus 1.7%, respectively. At the data cutoff, 97 and 121 patients died in these respective arms.

Researchers from the study also found that the pathological complete remission (achieving remission) rates among patients who underwent surgery in the perioperative chemotherapy group was 16.8%, compared with 10% in the neoadjuvant chemoradiation group.

Most patients in both the perioperative chemotherapy and neoadjuvant chemoradiation groups started neoadjuvant treatment. These patients comprised the predefined protocol population. A majority of patients in both groups completed neoadjuvant treatment (87.3% versus 67.7%) and received neoadjuvant treatment plus surgery (86.0% versus 82.9%). In the perioperative chemotherapy group, 63.3% of patients received adjuvant treatment and 52.5% completed adjuvant treatment.

Patients in the predefined protocol population in the perioperative chemotherapy (207 patients) and 196 patients in the neoadjuvant chemotherapy groups achieved a median OS of 66 months versus 39 months, respectively. The three-year OS rates were 58.1% versus 52.6%, respectively, and the five-year OS rates were 51.8% versus 40.5%, respectively.

“Perioperative chemotherapy with FLOT plus surgery improves OS compared with neoadjuvant chemoradiation plus surgery in patients with locally advanced, resectable esophageal adenocarcinoma. ESOPEC found that perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation ... for improving survival in resectable esophageal adenocarcinoma,” Hoeppner concluded in an oral presentation.

Editor's note: The article on the ESOPEC study was published on June 2, 2024, from the press briefing, and was updated on June 4, 2024, with additional information/data from the oral session.

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