Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer

Abstract

IMPORTANCE Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES The primary end point was overall survival. RESULTS In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. CONCLUSIONS AND RELEVANCE Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT00849615

Cancer of the gastroesophageal junction: a diagnosis, classification, and management review

“…GEJ tumors with small volume metastatic disease (oligometastatic) are increasingly being considered for combined modality treatment, including resection; however, these should be managed within the context of clinical trials.…”

Does hipec improve outcomes in gastric cancer patients treated with perioperative chemotherapy and radical surgery? A propensity‐score matched analysis

“…After propensity score analysis matched the two treatment groups, 5‐year and median OS in the HIPEC group and in the surgery alone was, respectively 11% vs 6% and 19 vs 12 months. It is noteworthy that in subgroup analysis patients from the HIPEC group were favored by the use of preoperative chemotherapy, confirming the role of systemic chemotherapy in these patients’ treatment …”

Surgical treatment of esophageal cancer in the era of multimodality management

“…A radical surgical resection of the primary tumor and the metastases can be performed in patients who respond well to multimodal chemotherapy. The recently published results of the FLOT 3 study show that patients with limited metastatic disease after four cycles of neoadjuvant chemotherapy followed by routine surgical resection have a favorable survival compared to patients who received eight cycles of chemotherapy and only a surgical intervention for a palliative indication . Patient selection for surgical resection was based on a realistic chance for R0 resection of the primary tumor and the possibility of at least a macroscopic complete resection of the metastatic lesions as evaluated by endoscopy and CT or MRI scans .…”

“…The recently published results of the FLOT 3 study show that patients with limited metastatic disease after four cycles of neoadjuvant chemotherapy followed by routine surgical resection have a favorable survival compared to patients who received eight cycles of chemotherapy and only a surgical intervention for a palliative indication . Patient selection for surgical resection was based on a realistic chance for R0 resection of the primary tumor and the possibility of at least a macroscopic complete resection of the metastatic lesions as evaluated by endoscopy and CT or MRI scans . To identify patients who would benefit from such an aggressive treatment, response to systemic treatment and the “test of time” (stable disease during follow‐up) are currently the only useful markers …”