eUpdate: Gastric Cancer Treatment Recommendations

eUpdate – Gastric Cancer Treatment Recommendations

Published: 4 November 2019. Authors: ESMO Guidelines Committee

Note: Other eUpdates have been published for these guidelines. All currently valid eUpdates can be accessed from the page displaying the  full guidelines on this topic.

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 advanced/metastatic disease, second- and further-line treatment

Text update

This sentence:

“Treatment options may be used sequentially in second and third line, but there is no clear evidence for a benefit beyond second line treatment.”

Is replaced with:

In a phase III randomised trial of patients with chemorefractory gastric cancer (patient treated with at least two prior lines of chemotherapy), trifluridine/tipiracil improved overall survival (OS) compared to placebo {OS 5.7 versus 3.6 months hazard ratio (HR) 0.69 [95% confidence interval (CI) 0.56–0.85], two-sided P=0.00058}.

Recommendation:

Third-line chemotherapy with trifluridine/tipiracil is recommended for patients who are of PS 0–1 [I, A].

Section

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

The ESMO-MCBS table published in the eUpdate on Gastric Treatment Recommendations published on 6 May 2019 is updated to include a new line for trifluidine/tipiracil.

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

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

Docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT)

 

Patients 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 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 [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)
Trifluridine/ tipiracil Patients who have been treated with two prior lines of chemotherapy 

Randomised, double-blind, phase 3 study evaluating TAS-102 plus BSC versus placebo plus BSC in patients with metastatic gastric cancer refractory to standard treatments [3] 

NCT02500043

Placebo

OS: 3.6 months

OS gain: 2.1 months

 

OS HR:  0.69 (0.56-0.85)   3 (Form 2a)

aEMA approvals since January 2016, except docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT).
bESMO-MCBS version 1.1 [4]. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee.

AE, adverse event; BSC, best supportive care; CI, confidence interval; EMA, European Medicines Agency; ESMO-MCBS, ESMO-Magnitude of Clinical Benefit Scale; FLOT, 5-fluorouracil/leucovorin, oxaliplatin, docetaxel; HR, hazard ratio; OS, overall survival; QoL, quality of life; TAS, trifluridine/tipiracil.

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 SE, 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; 393: 1948–1195.
  3. Shitara K, Doi T, Dvorkin M et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(11): 1437–1448.
  4. Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017; 28: 2340–2366.