Ramucirumab in combination with paclitaxel as second-line treatment for adult patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Ramucirumab in combinatie

KCE has read for you

Nadia Benahmed, Lorena San Miguel

Main messages

The European network for Health Technology Assessment (EUnetHTA) published in June 2015 a systematic review on the clinical effectiveness and safety of the combination of ramucirumab (Cyramza®) and paclitaxel (RP) in adult patients with advanced gastric or gastro-oesophageal junction adenocarcinoma1, previously treated with chemotherapy and with good performance status.

Five randomized controlled trials (RCT) were included in the review: one offering a direct comparison of the combination RP versus placebo plus paclitaxel (PP) and four others allowing indirect comparisons between the combinations RP and, docetaxel, irinotecan and best supportive care.

The review concludes that RP is more effective than paclitaxel alone, and presents a similar safety profile.

No statistically significant differences in clinical effectiveness or safety are found between RP and docetaxel. While the safety profile is similar, irinotecan is significantly less effective than RP. Finally, RP significantly improves overall survival in comparison with PP and with best supportive care.

Background and scope

The overall objective of the EunetHTA Joint Action is to foster collaboration and knowledge sharing between European public HTA agencies, with the aim of increasing the efficiency and quality of technology assessments and promoting their uptake in the national health policy decision-making processes. The present assessment is one of the pilot joint assessments using the EUnetHTA Core model® for Rapid Relative Effectiveness Assessment of pharmaceuticals (more info: www.eunethta.eu).

The objective of this EUnetHTA review was to assess the effectiveness and safety of RP compared to other treatments for adults with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma previously treated with chemotherapy and with good performance status (Eastern Cooperative Oncology Group (ECOG) score 0 or 1). Gastric cancers are rare malignancies arising from the lining of the stomach while cancer of the gastro-oesophageal junction occurs within 5 cm proximal and distal of the anatomic cardia.

The main outcomes used in the review were overall survival, progression-free survival, and objective response rate. In addition, quality of life and safety (adverse events) were also evaluated.

The quality of the EUnetHTA review was independently appraised by two KCE researchers by means of the AMSTAR tool, which resulted in a score of 7/11.


Several databases, conference abstracts from the European Society for Medical Oncology and the American Society of Clinical Oncology as well as manufacturer sources were consulted up to December 2013. Study types were limited to RCTs.
Five randomized controlled trials (RCTs) were included in the review, but only one of them (the RAINBOW trial) provided a direct comparison of RP with PP.

The remaining four were used to allow indirect comparisons by means of the Bucher network analysis method. They compared in one hand irinotecan with, one the other hand, paclitaxel, docetaxel or best supportive care, and the last trials confronted docetaxel with active symptom control.



  • Overall survival (OS)

Risk of death from any cause is significantly reduced by 19% (Hazard ratio (95% Confidence Interval) HR (95% CI) 0.81 (0.68 - 0.96); p=0.0169) when RP is compared to PP. Median OS was 9.63 months (8.6 - 10.8) among patients treated with RP compared with 7.36 months
(6.3 - 8.4) among those treated with PP.

Indirect comparisons showed that hazard ratios favoured RP and were statistically significant when compared to irinotecan and best supportive care, while there was no significant difference when RP was compared to docetaxel.

  • Objective response rate (ORR)

The comparison of RP versus PP gave an HR for ORR (95% CI) of 2.81 (1.38 - 2.93). Partial response rate was 28% and 16%, respectively for patients treated with RP and PP. However, complete response was achieved in only 0.6% and 0.3%, respectively.

The HR favoured RP when compared to irinotecan. No statistically significant difference was observed between RP and docetaxel.

  • Progression-free survival (PFS)

Median PFS (95% CI) was 4.4 months (4.2 - 5.3) in the RP group and 2.9 months (2.8 - 3.0) in the PP group. The HR for RP was lower compared to irinotecan and not statistically significantly different when compared with docetaxel.


The RAINBOW trial did not find differences between the groups in withdrawal due to adverse events, frequency of serious adverse events or adverse events leading to death. Indirect evidence was too limited to inform the network analysis and therefore it is not discussed further.

Quality of life

Quality of life was maintained longer in patients treated with RP compared to those treated with PP.


Patients with advanced gastric cancer have a poor prognosis, with a life expectancy of less than a year. The Belgian Cancer Registry reported in 764 patients with gastric or gastro-oesophageal junction adenocarcinoma in stage III or IV in 2012.

The EUnetHTA review concludes that RP improves median overall survival and progression-free survival with approximately 2 months, and favourably influences response rate and quality of life in comparison with PP, with a similar safety profile. The limited data that could be drawn from indirect comparisons between RP and interventions other than paclitaxel, were insufficient to offer robust conclusions.

A decision on the reimbursement of ramucirumab (CYRAMZA®) is still pending at the Belgian Drug Reimbursement Committee.


1. EUnetHTA. Ramucirumab in combination with paclitaxel as second-line treatment for adult patients with advanced gastric or gastro-oesophageal junction adenocarcinoma. 2015. Pilot ID: WP5 – SA4 http://www.eunethta.eu/sites/5026.fedimbo.belgium.be/files/WP5-SA-4_RAMU...

What is KCE has read for you?


KCE has read for you synthesises a recently published high-quality systematic review or health technology assessment with relevance for the Belgian health system.

The original publication was appraised and contextualised by KCE researchers. KCE has read for you is not based on original research conducted by KCE.

More details on methodology can be found on the KCE website.


This document includes

  • Key findings of the publication under evaluation
  • A contextualisation within the Belgian healthcare system

Not included

  • Recommendations
  • Detailed descriptions


Trustworthy original publication

The methodological quality of the systematic review was assessed with the AMSTAR tool.

Gudrun BRIAT (NL)
Communication Manager for the KCE
+32 (0)2 287 33 54 (FR: 33 48)
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