trialsTrialPositive

REACH-2

REACH-2 showed that the antibody ramucirumab helped people with liver cancer live longer after sorafenib, but only when a blood marker, alpha-fetoprotein, was high, making it the first liver cancer drug approved on a biomarker.

The earlier REACH trial of ramucirumab, an antibody against VEGF receptor 2, missed its overall survival endpoint in the whole population but showed a benefit in patients with an alpha-fetoprotein of 400 ng/mL or more. REACH-2 tested exactly that group: patients with advanced hepatocellular carcinoma who had progressed on or were intolerant of sorafenib were randomised two to one to ramucirumab or placebo, with overall survival as the primary endpoint.

Ramucirumab lengthened overall survival and progression-free survival compared with placebo, confirming the biomarker hypothesis, and was approved in the United States in May 2019 for this population, the first biomarker-selected approval in hepatocellular carcinoma.

Setting

Advanced hepatocellular carcinoma after sorafenib with a baseline alpha-fetoprotein of 400 ng/mL or more: ramucirumab against placebo

Phase

Phase 3

Sponsor

Eli Lilly

Registry

NCT02435433

Headline result

Ramucirumab improved overall survival over placebo in alpha-fetoprotein-high hepatocellular carcinoma after sorafenib; approved in May 2019.

Started

2015-07-20

Reported

2019

Enrolled

Outcomes

4top

In plain words

What these results mean for people, not percentages

Overall survivalprimarysurvival endpoint

Median 8.5 vs 7.3 months with Ramucirumab 8 mg/kg compared with Placebo; about 1.2 months longer for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 29 percent lower chance of the event at any given time (hazard ratio 0.71, likely range 0.531 to 0.949).

Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Progression-free survivalsurrogate endpoint

Median 2.8 vs 1.6 months with Ramucirumab 8 mg/kg compared with Placebo; about 1.2 months longer for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 55 percent lower chance of the event at any given time (hazard ratio 0.452, likely range 0.339 to 0.603).

This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Objective responseresponse endpoint

5 vs 1 out of 100 had their tumour shrink with Ramucirumab 8 mg/kg compared with Placebo; 4 more per 100.
Roughly one extra person helped for every 25 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

The p-value (0.1697) means the difference could plausibly be due to chance.
A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.

Grade 3 or worse hypertensionother endpoint

13 vs 5 out of 100 reached this endpoint with Ramucirumab 8 mg/kg compared with Placebo; 8 more per 100.
Roughly one extra person helped for every 13 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Caveats

These results apply to the people the trial enrolled: Advanced hepatocellular carcinoma after sorafenib with a baseline alpha-fetoprotein of 400 ng/mL or more: ramucirumab against placebo. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

Overall survivalprimary

HR 0.71 (0.531 to 0.949) · p = 0.0199

Download

Median follow-up 7.6 months

Source

Progression-free survival

HR 0.452 (0.339 to 0.603) · p <0.0001

Download

Source

Objective response

· p = 0.1697

Ramucirumab 8 mg/kg5 of 100

n = 197

Placebo1 of 100

n = 95

Download

Source

Grade 3 or worse hypertension

Ramucirumab 8 mg/kg13 of 100

n = 197

Placebo5 of 100

n = 95

Download

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Overall survivalprimary	Ramucirumab 8 mg/kg	197	8.5 months	0.71 (0.531 to 0.949)	0.0199	link
Overall survivalprimary	Placebo	95	7.3 months	0.71 (0.531 to 0.949)	0.0199	link
Progression-free survival	Ramucirumab 8 mg/kg	197	2.8 months	0.452 (0.339 to 0.603)	<0.0001	link
Progression-free survival	Placebo	95	1.6 months	0.452 (0.339 to 0.603)	<0.0001	link
Objective response	Ramucirumab 8 mg/kg	197	5%	-	0.1697	link
Objective response	Placebo	95	1%	-	0.1697	link
Grade 3 or worse hypertension	Ramucirumab 8 mg/kg	197	13%	-	-	link
Grade 3 or worse hypertension	Placebo	95	5%	-	-	link

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cancers

Advanced hepatocellular carcinoma (BCLC C)Hepatocellular carcinoma

technologies

Anti-angiogenic therapy Monoclonal antibodies

drugs

ApprovedMonoclonal antibody (anti-VEGFR2)

Ramucirumab · Cyramza

companies

Eli Lilly (incl. Loxo)

people

Andrew X. Zhu

Evidence strength70/100 · Solid

How much and what kind of evidence, not how big the benefit. Click for the breakdown.

Phase 3+30
Primary endpoint: overall survival+20
Result: positive+15
No independent replication recorded0
A linked product is approved+5

Formula disclosed on the evidence page.

ProvenanceLast edited 2026-09-22 · Jude Gomila · Wave 2 corpus-only joins applied · diff · file

Sources & links

ClinicalTrials.gov NCT02435433

REACH-2

Setting

Advanced hepatocellular carcinoma after sorafenib with a baseline alpha-fetoprotein of 400 ng/mL or more: ramucirumab against placebo

Phase

Phase 3

Sponsor

Eli Lilly

Registry

NCT02435433

Headline result

Ramucirumab improved overall survival over placebo in alpha-fetoprotein-high hepatocellular carcinoma after sorafenib; approved in May 2019.

Started

2015-07-20

Reported

2019

Enrolled

Outcomes

4top

In plain words

What these results mean for people, not percentages

Overall survivalprimarysurvival endpoint

Median 8.5 vs 7.3 months with Ramucirumab 8 mg/kg compared with Placebo; about 1.2 months longer for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 29 percent lower chance of the event at any given time (hazard ratio 0.71, likely range 0.531 to 0.949).

Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Progression-free survivalsurrogate endpoint

Median 2.8 vs 1.6 months with Ramucirumab 8 mg/kg compared with Placebo; about 1.2 months longer for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 55 percent lower chance of the event at any given time (hazard ratio 0.452, likely range 0.339 to 0.603).

This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Objective responseresponse endpoint

5 vs 1 out of 100 had their tumour shrink with Ramucirumab 8 mg/kg compared with Placebo; 4 more per 100.
Roughly one extra person helped for every 25 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

The p-value (0.1697) means the difference could plausibly be due to chance.
A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.

Grade 3 or worse hypertensionother endpoint

13 vs 5 out of 100 reached this endpoint with Ramucirumab 8 mg/kg compared with Placebo; 8 more per 100.
Roughly one extra person helped for every 13 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Caveats

These results apply to the people the trial enrolled: Advanced hepatocellular carcinoma after sorafenib with a baseline alpha-fetoprotein of 400 ng/mL or more: ramucirumab against placebo. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

Overall survivalprimary

HR 0.71 (0.531 to 0.949) · p = 0.0199

Download

Median follow-up 7.6 months

Source

Progression-free survival

HR 0.452 (0.339 to 0.603) · p <0.0001

Download

Source

Objective response

· p = 0.1697

Ramucirumab 8 mg/kg5 of 100

n = 197

Placebo1 of 100

n = 95

Download

Source

Grade 3 or worse hypertension

Ramucirumab 8 mg/kg13 of 100

n = 197

Placebo5 of 100

n = 95

Download

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Overall survivalprimary	Ramucirumab 8 mg/kg	197	8.5 months	0.71 (0.531 to 0.949)	0.0199	link
Overall survivalprimary	Placebo	95	7.3 months	0.71 (0.531 to 0.949)	0.0199	link
Progression-free survival	Ramucirumab 8 mg/kg	197	2.8 months	0.452 (0.339 to 0.603)	<0.0001	link
Progression-free survival	Placebo	95	1.6 months	0.452 (0.339 to 0.603)	<0.0001	link
Objective response	Ramucirumab 8 mg/kg	197	5%	-	0.1697	link
Objective response	Placebo	95	1%	-	0.1697	link
Grade 3 or worse hypertension	Ramucirumab 8 mg/kg	197	13%	-	-	link
Grade 3 or worse hypertension	Placebo	95	5%	-	-	link

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Shares Anti-angiogenic therapy and the tag subtype-trials.
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Shares Monoclonal antibodies and the tag subtype-trials.
Trial
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Shares Anti-angiogenic therapy and the tag subtype-trials.
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REGOBONE
Shares Anti-angiogenic therapy and the tag subtype-trials.

cancers

Advanced hepatocellular carcinoma (BCLC C)Hepatocellular carcinoma

technologies

Anti-angiogenic therapy Monoclonal antibodies

drugs

ApprovedMonoclonal antibody (anti-VEGFR2)

Ramucirumab · Cyramza

companies

Eli Lilly (incl. Loxo)

people

Andrew X. Zhu

Evidence strength70/100 · Solid

How much and what kind of evidence, not how big the benefit. Click for the breakdown.

Phase 3+30
Primary endpoint: overall survival+20
Result: positive+15
No independent replication recorded0
A linked product is approved+5

Formula disclosed on the evidence page.

ProvenanceLast edited 2026-09-22 · Jude Gomila · Wave 2 corpus-only joins applied · diff · file

Sources & links

ClinicalTrials.gov NCT02435433

REACH-2

Outcomes

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