Neoadjuvant FLOT, Surgical Resection Feasible For Gastric Cancer With Limited Metastases

Patients with limited metastatic disease may benefit from neoadjuvant chemotherapy and resection of gastric or gastro-oesophageal junction adenocarcinoma

medwireNews: AIO-FLOT3 study findings indicate that patients with limited metastatic gastric or gastro-oesophageal junction cancer may benefit from neoadjuvant chemotherapy and surgical resection.

“Within the limitations of a nonrandomized phase 2 study, the results reported here showed that the concept was feasible and provided a rationale for an ongoing, randomized, phase 3 trial”, say Salah-Eddin Al-Batran, from the Institute of Clinical Cancer Research in Frankfurt, Germany, and co-investigators.

In all, 252 patients with treatment-naïve gastric or gastro-oesophageal junction adenocarcinoma attending one of 52 German cancer centres between 2009 and 2010 underwent imaging and were assigned to one of three groups according to whether they had resectable primary tumours (group A, n=51), limited metastases (group B, n=60) or extensive metastases (group C, n=127).

Patients in group A were given four cycles of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) before and after surgery, while those in group C were offered FLOT chemotherapy and palliative surgery where necessary.

Group B patients were given four cycles of FLOT and offered surgery if further imaging suggested that margin-free (R0) surgery had become possible for the primary tumour, with at least macroscopic complete resection of the metastases.

Almost half of the patients in group B had metastases restricted to the retroperitoneal lymph nodes (45.0%), while the remainder had liver (18.3%) or lung (16.7%) involvement, localised peritoneal involvement (6.7%) or other incurable sites of disease (13.3%).

Median overall survival (OS) was significantly higher for patients in group B than group C, at 22.9 versus 10.7 months, the researchers report in JAMA Oncology. Median OS was not achieved at time of publication in group A, but “compared favorably” with group B, they say.

Patients in group B had a 60.0% response rate to FLOT, with 10.0% showing a complete response and 50.0% a partial response, whereas just 43.3% of patients in group C responded to treatment.

In all, 96.1% of group A, 60.0% of group B and 11.8% of group C underwent resection, with R0 outcomes of the primary tumour achieved in 81.6%, 80.6% and 33.3% of cases, respectively.

Group B patients who underwent surgery had a median OS of 31.3 months versus 15.9 months for those who did not and progression-free survival was also longer in patients who received resection, at 26.7 vs 8.4 months.

“The most common reason for not assigning patients to surgery was the investigator’s decision that metastatic lesions were unresectable or incurable after neoadjuvant chemotherapy”, the investigators explain, and thus patients given surgery were therefore “superselected”.

“Nevertheless, within these limitations, the considerable survival in the surgical group of arm B remains promising”, they write. “A median survival of 31 months is more than we would expect in a superselected group of patients with metastatic disease.”

Further analysis showed that group B patients who had only retroperitoneal lymph node metastases had the best survival. But those with liver disease had the poorest survival, leading the authors to recommend “to either exclude this group in future trials or limit the group to patients in whom complete (R0) resection is judged possible at initial evaluation.”

“Nevertheless, few patients with metastatic gastric cancer will have initially resectable liver disease”, they conclude.

Reference

Al-Batran S-E, Homann N, Pauligk C, et al. Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer. The AIO-FLOT3 trial. JAMA Oncol; Advance online publication 27 April 2017. doi:10.1001/jamaoncol.2017.0515

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