eUpdate: Gastric Cancer Treatment Recommendations

eUpdate – Gastric Cancer Treatment Recommendations

Published: 6 May 2019. Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to the Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Smyth EC, Verheij M, Allum W, et al. Ann Oncol 2016; 27 (Suppl 5): v38-v49.

Section

Management of local/locoregional disease – Perioperative chemotherapy

Recommendation update

Perioperative (pre- and postoperative) chemotherapy with FLOT (5-fluorouracil/leucovorin, oxaliplatin, docetaxel) is recommended for patients with ≥ Stage IB resectable gastric and gastroesophageal junction cancers [I, A; ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.1 score A].

Text update

A study of the German AIO study group investigating a perioperative FLOT regimen (5-fluorouracil/leucovorin, oxaliplatin, docetaxel) versus ECF/X demonstrated higher rates of pathological response for FLOT (15.6% versus 5.8%) [38]. This study has now reported a significant improvement in its primary endpoint of overall survival (HR 0.77; P=0.012; with median overall survival for FLOT 50 months versus 35 months for ECF/ECX) with no major concerns for toxicity [38b].Based on these data, the perioperative use of FLOT should be regarded as standard of care, unless there is a formal contraindication for the use of any of its components or the patient is not suitable for triplet chemotherapy. Currently, there is no evidence to support the perioperative use of any biologically targeted drug, including trastuzumab or any antiangiogenic compounds.

References

A new reference 38 is added to replace the original 38

38. Al-Batran SE, Hofheinz RD, Pauligk C, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; 17:1697-1708.

New reference 38b (inserted before original manuscript reference 39)

38b. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019; http://dx.doi.org/10.1016/S0140-6736(18)32557-1 [Epub ahead of print].

ESMO-Magnitude of Clinical Benefit Scale (MCBS) table for new therapies in gastric cancer

Therapy Disease setting Trial Control Absolute survival gain HR (95% CI) Qol/Toxicity

MCBS

scorea

Docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT) Patients with with resectable gastric or gastro-oesophageal junction adenocarcinoma who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both

Perioperative chemotherapy with fluorouracil plusleucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial [1, 2]

Phase III

NCT01216644

Epirubicin, cisplatin, and fluorouracil or capecitabine

Median OS:35 months

OS at 3 years: 48%

Median
OS gain:15 months

OS gain at 3 years: 9%

OS HR:0.77 (0.63–0.94)

QoL not available

AEs similar

A (Form 1)

aESMO-MCBS version 1.1 [3]
AE, adverse event; CI, confidence interval; EMA, European Medicines Agency; HR, hazard ratio; MCBS, Magnitude of Clinical Benefit Scale; OS, overall survival; QoL, quality of life.

References

  1. Al-Batran SE, Hofheinz RD, Pauligk C, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; 17:1697-1708.
  2. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019; http://dx.doi.org/10.1016/S0140-6736(18)32557-1 [Epub ahead of print].
  3. Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017; 28: 2340-2366.