Quick Takes on Studies in Noncolorectal Gastrointestinal Cancers


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In this roundup, The ASCO Post offers a glance at key findings from studies in noncolorectal gastrointestinal malignancies presented at the European Society for Medical Oncology (ESMO) 2017 Congress from investigators around the world.

Docetaxel-Based Triplet in Gastric Cancer

The superiority of docetaxel-based triplet therapy over standard care in patients with resectable esophagogastric cancer was confirmed by the phase III FLOT4 trial. In an update, researchers reported the first results of multivariate, subgroup, and sensitivity analyses.1

The study randomized 716 patients with resectable gastric or gastroesophageal junction adenocarcinoma to receive either 3 preoperative and 3 postoperative 3-week cycles of ECF/ECX (epirubicin, cisplatin, and fluorouracil [5-FU] or capecitabine) or 4 perioperative and 4 postoperative 2-week cycles of FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU). The primary endpoint was overall survival.

Median overall survival was 50 months in the FLOT arm vs 35 months in the ECF/ECX arm (hazard ratio = 0.77; P = .012), and median progression-free survival was 30 vs 18 months, respectively (HR = 0.75; P = .001). FLOT was also associated with less progressive disease occurring during or after preoperative therapy, more R0 resections, and a higher number of pathologic T0/T1 tumors, reported Salah-Eddin Al-Batran, MD, of the UCT-University Cancer Centre at Krankenhaus Nordwest in Frankfurt, Germany.


These new analyses confirm the superiority of FLOT [docetaxel, oxaliplatin, leucovorin, and 5-FU], which is the new standard of care in the perioperative treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma.
— Salah-Eddin Al-Batran, MD

The relative effect of FLOT was observed in all subgroups, including the elderly and patients with signet cell tumors, and was particularly pronounced in Siewert type 1 esophageal cancers (HR = 0.60), Barrett tumors (HR = 0.62), small tumors (HR = 0.66), and node-negative disease (HR = 0.64).

“These new analyses confirm the superiority of FLOT, which is the new standard of care in the perioperative treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma,” Dr. Al-Batran said. “Some oncologists believe that patients with small tumors and those with signet cell cancer should not be treated preoperatively, but the results of the FLOT4 trial contradict this and show these patients do benefit.”

Michel Ducreux, MD

Michel Ducreux, MD

ESMO spokesperson Michel Ducreux, MD, of Gustave Roussy in Villejuif, France, commented that the FLOT regimen is less toxic than ECF and more convenient, with one 24-hour infusion every 2 weeks rather than continuous infusion of 5-FU with ECF.

“The new analysis shows that the advantage of the FLOT regimen is seen across all subgroups and shows that FLOT is clearly the new standard of care,” Dr. Ducreux concluded. “FLOT will be the best backbone of chemotherapy that we can use in this setting. A step forward would be to try to improve the results by adding targeted therapies or immune checkpoint inhibitors. It would also be interesting to know if the FLOT regimen shows different levels of effectiveness in the four molecular biologic subgroups of gastric cancer.”

Eryaspase Plus Chemotherapy in Metastatic Pancreatic Cancer

The addition of eryaspase, which is L-asparaginase encapsulated in red blood cells, to chemotherapy as second-line treatment of metastatic pancreatic cancer led to statistically significant improvements in both progression-free and overall survival.2 As carriers for asparaginase, erythrocytes can prolong asparaginase activity and reduce toxicity, and this process is further enhanced through encapsulation, researchers explained at the ESMO 2017 Congress.


The full results of this study support eryaspase [plus chemotherapy] as a potential treatment option for patients with metastatic pancreatic cancer in the second-line setting.
— Pascal Hammel, MD

In a multicenter randomized phase IIb study of 141 patients, eryaspase added to gemcitabine or FOLFOX (leucovorin, 5-FU, oxaliplatin), compared with chemotherapy alone, improved median overall survival from 19.0 to 26.1 weeks (HR = 0.60; P = .009). One-year survival rates were 14.8% vs 3.0%, respectively, reported Pascal Hammel, MD, of Beaujon Hospital in Paris.

Median progression-free survival was 8.6 weeks with chemotherapy plus eryaspase vs 7.0 weeks with chemotherapy alone (HR = 0.59; P = .011), with 16.9% and 5.8%, respectively, being free of disease progression at 24 weeks. Response rates and disease control rates were also significantly improved with eryaspase. 

Asparagine synthetase expression is believed to play a role in sensitivity to this treatment. Patients with high-asparagine synthetase–expressing tumors had a worse prognosis but also a better relative treatment benefit. The hazard ratio for overall survival in this subset was 0.45, and it was 0.65 for low-expressing tumors. Disease control rates were 51.7% vs 7.1%, respectively, in the high-asparagine synthetase–expressing group.

The treatment was well tolerated. The proportion of patients with at least one serious adverse event was 45% in the eryaspase arm compared with 50% in the control arm.

“The full results of this study are highly encouraging and support eryaspase as a potential treatment option for patients with metastatic pancreatic cancer in the second-line setting,” Dr. Hammel commented. A global phase III study is being planned.

Minimally Invasive Esophagectomy

In the multicenter, randomized MIRO trial of 207 patients with resectable esophageal cancer, postoperative morbidity was substantially reduced and there was a trend toward better survival in those who underwent a minimally invasive procedure vs open surgery.3

Guillaume Piessen, MD, PhD

Guillaume Piessen, MD, PhD

The study compared transthoracic open esophagectomy with hybrid minimally invasive (laparoscopic) esophagectomy. The latter consists of an Ivor Lewis procedure with laparoscopic gastric mobilization and open right thoracotomy. Postoperative morbidity at 30 days, the primary endpoint, was significantly higher in the open esophagectomy group than in the laparoscopic group: 64.4% vs 35.9% (odds ratio [OR] = 0.31; P < .001), as were pulmonary complications, which occurred in 30.1% vs 17.7%, respectively (P = .037), reported Guillaume Piessen, MD, PhD, of the University Hospital C. Huriez Place de Verdun in Lille, France.

At 3 years, there was also a trend for improved survival with minimally invasive surgery: 67.0% vs 54.8% in the open esophagectomy arm (P = .054), showing “this is an oncologically sound procedure,” Dr. Piessen commented. Although the survival endpoint was not statistically significant, it is “highly clinically relevant,” he maintained.


Hybrid minimally invasive esophagectomy should become the new standard surgical procedure for patients with tumors in the middle or lower third of the esophagus.
— Ulrich Güller, MD, MHS, FEBS

ESMO spokesperson Ulrich Güller, MD, MHS, FEBS, of Kantonsspital St. Gallen, Switzerland, called the study “extremely important, well designed, and well conducted.” Based on these results, he added, hybrid minimally invasive esophagectomy should become the new standard surgical procedure for patients with tumors in the middle or lower third of the esophagus. 

Dr. Güller added: “I think it is key to mention Christophe -Mariette, MD, PhD, the first author of this important trial, who sadly passed away a few months ago. Prof. Mariette was a model of a surgical scientist and an opinion leader in the field, and his contribution to the MIRO trial was of cardinal importance.” ■

DISCLOSURE: Drs. Al-Batran, Ducreux, Piessen, and Güller reported no conflicts of interest. Dr. -Hammel has received honorarium and travel expenses from Erythec.

REFERENCES

1. Al-Batran S-E, Pauligk C, Homann N, et al: Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: Updated results from multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO). 2017 ESMO Congress. Abstract LBA27_PR. Presented September 8, 2017.

2. Hammel P, Bachet J, Portales F, et al: A phase 2b study of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma. 2017 ESMO Congress. Abstract 621PD. Presented September 11, 2017.

3. Mariette C, Markar S, Dabakuyo-Yonli T, et al: Hybrid minimally invasive vs. open esophagectomy for patients with esophageal cancer: Long-term outcomes of a multicenter, open-label, randomized phase III controlled trial, the MIRO trial. 2017 ESMO Congress. Abstract 615O_PR. Presented September 8, 2017.



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