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NALA

NALA showed that the irreversible HER2 inhibitor neratinib, given with capecitabine, kept heavily pretreated HER2-positive breast cancer under control for longer than lapatinib and reduced the need for treatment of brain metastases.

Positive

NALA randomised 621 patients with HER2-positive metastatic breast cancer who had received two or more prior HER2-directed regimens to neratinib plus capecitabine or lapatinib plus capecitabine. The co-primary endpoints were progression-free and overall survival.

Neratinib improved progression-free survival, with a smaller and non-significant difference in overall survival, and fewer patients needed intervention for central nervous system metastases. Diarrhoea was the dominant toxicity and requires prophylaxis. The regimen was approved in the United States in February 2020 for third-line or later HER2-positive metastatic disease.

Setting

HER2-positive metastatic breast cancer after two or more HER2-directed regimens: neratinib plus capecitabine against lapatinib plus capecitabine

Phase

Phase 3

Sponsor

Puma Biotechnology

Registry

NCT01808573

Headline result

Neratinib plus capecitabine improved progression-free survival over lapatinib plus capecitabine and reduced interventions for central nervous system disease; approved in February 2020.

Started

2013-03-29

Reported

2020

Enrolled

621 enrolled

Outcomes

In plain words

What these results mean for people, not percentages

621 enrolled

Progression-free survival (central review)primarysurrogate endpoint

The treated group had about 24 percent lower chance of the event at any given time (hazard ratio 0.76).
The absolute difference, how many more people out of 100 were helped, is not reported here.
Medians not reported in the abstract

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.

Overall survivalprimarysurvival endpoint

The treated group had about 12 percent lower chance of the event at any given time (hazard ratio 0.88).
The absolute difference, how many more people out of 100 were helped, is not reported here.

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Objective response rateresponse endpoint

32.8 vs 26.7 out of 100 had their tumour shrink with Neratinib + capecitabine compared with Lapatinib + capecitabine; 6.1 more per 100.
Roughly one extra person helped for every 16 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

The p-value (0.1201) 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.

Duration of responseother endpoint

Median 8.5 vs 5.6 months with Neratinib + capecitabine compared with Lapatinib + capecitabine; about 2.9 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 50 percent lower chance of the event at any given time (hazard ratio 0.5, likely range 0.33 to 0.74).

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

Intervention for CNS disease (cumulative incidence)other endpoint

22.8 vs 29.2 out of 100 reached this endpoint with Neratinib + capecitabine compared with Lapatinib + capecitabine; 6.4 fewer per 100.
On this measure the first group did worse, not better.

The p-value (0.043) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Diarrhoea (all grades)other endpoint

83 vs 66 out of 100 reached this endpoint with Neratinib + capecitabine compared with Lapatinib + capecitabine; 17 more per 100.
Roughly one extra person helped for every 6 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: HER2-positive metastatic breast cancer after two or more HER2-directed regimens: neratinib plus capecitabine against lapatinib plus capecitabine. People in a different situation may not see the same effect.
The trial selected people by a biomarker (HER2); the result should not be assumed for people whose cancer does not have it.

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.

621 enrolled.

Progression-free survival (central review)primary

HR 0.76 (0.63 to 0.93) · p = 0.0059

Medians not reported in the abstract

Source

Overall survivalprimary

HR 0.88 (0.72 to 1.07) · p = 0.2098

Numbers not yet public.

Source

Objective response rate

· p = 0.1201

Neratinib + capecitabine32.8 of 100

n = 307

Lapatinib + capecitabine26.7 of 100

n = 314

Download

Source

Duration of response

HR 0.5 (0.33 to 0.74) · p = 0.0004

Download

Source

Intervention for CNS disease (cumulative incidence)

· p = 0.043

Neratinib + capecitabine22.8 of 100

n = 307

Lapatinib + capecitabine29.2 of 100

n = 314

Download

Source

Diarrhoea (all grades)

Neratinib + capecitabine83 of 100

n = 307

Lapatinib + capecitabine66 of 100

n = 314

Download

Loperamide prophylaxis

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Progression-free survival (central review)primary	Neratinib + capecitabine	307	Medians not reported in the abstract	0.76 (0.63 to 0.93)	0.0059	link
Progression-free survival (central review)primary	Lapatinib + capecitabine	314	-	0.76 (0.63 to 0.93)	0.0059	link
Overall survivalprimary	Neratinib + capecitabine	307	-	0.88 (0.72 to 1.07)	0.2098	link
Overall survivalprimary	Lapatinib + capecitabine	314	-	0.88 (0.72 to 1.07)	0.2098	link
Objective response rate	Neratinib + capecitabine	307	32.8%	-	0.1201	link
Objective response rate	Lapatinib + capecitabine	314	26.7%	-	0.1201	link
Duration of response	Neratinib + capecitabine	307	8.5 months	0.5 (0.33 to 0.74)	0.0004	link
Duration of response	Lapatinib + capecitabine	314	5.6 months	0.5 (0.33 to 0.74)	0.0004	link
Intervention for CNS disease (cumulative incidence)	Neratinib + capecitabine	307	22.8%	-	0.043	link
Intervention for CNS disease (cumulative incidence)	Lapatinib + capecitabine	314	29.2%	-	0.043	link
Diarrhoea (all grades)	Neratinib + capecitabine	307	83%	-	-	link
Diarrhoea (all grades)	Lapatinib + capecitabine	314	66%	-	-	link

Taking part

NCT01808573completed

Run by: Puma Biotechnology, Inc.
Open to: 18 Years and over, any sex
Enrolment: 621
Sites: 252
Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Netherlands, Portugal, Russia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Registry updated: 2021-06-11

The full inclusion and exclusion criteria are on the registry record. Read 2026-10-07. Recruiting overall does not mean a particular site is open; ask the study team.

ClinicalTrials.gov data courtesy of the US National Library of Medicine.

Key papers

rctJournal of Clinical Oncology 2020476 citations

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

This is the paper Europe PMC returns for registry id NCT01808573 with the most citations, so it is the natural first reading for anyone following the NALA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.

Connected

Trial
TUXEDO-1
Shares HER2-positive breast cancer with brain metastases, HER2-positive breast cancer, Breast cancer (all types) and the tag subtype-trials.
Trial
ATEMPT
Shares HER2-positive breast cancer, Breast cancer (all types) and the tag subtype-trials.
Trial
PATINA
Shares HER2-positive breast cancer, Breast cancer (all types) and the tag subtype-trials.
Trial
GeparSixto
Shares Lapatinib, Breast cancer (all types) and the tag subtype-trials.
Trial
BOLERO-2
Shares Breast cancer (all types), Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
HERACLES
Shares Lapatinib and the tag subtype-trials.
Trial
CARMENA
Shares Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
TAM-01
Shares Breast cancer (all types) and the tag subtype-trials.

cancers

Breast cancer (all types)HER2-positive breast cancer HER2-positive breast cancer with brain metastases

technologies

HER2 tyrosine kinase inhibitors Small-molecule kinase inhibitors

drugs

ApprovedOral fluoropyrimidine prodrug (antimetabolite)

Capecitabine · Xeloda

ApprovedSmall-molecule reversible HER2/EGFR kinase inhibitor

Lapatinib · Tykerb

ApprovedSmall-molecule irreversible pan-HER kinase inhibitor

Neratinib · Nerlynx

Sources

Every source this page cites, grouped by who published it. Grouping is read from the web address, not assigned by hand.

ClinicalTrials.gov · 1

ClinicalTrials.gov NCT01808573

A source that has moved or gone is reported by the weekly link check. /audit/

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

Sourced, not expert-reviewed

NALA

Positive

Setting

HER2-positive metastatic breast cancer after two or more HER2-directed regimens: neratinib plus capecitabine against lapatinib plus capecitabine

Phase

Phase 3

Sponsor

Puma Biotechnology

Registry

NCT01808573

Headline result

Neratinib plus capecitabine improved progression-free survival over lapatinib plus capecitabine and reduced interventions for central nervous system disease; approved in February 2020.

Started

2013-03-29

Reported

2020

Enrolled

621 enrolled

Outcomes

In plain words

What these results mean for people, not percentages

621 enrolled

Progression-free survival (central review)primarysurrogate endpoint

The treated group had about 24 percent lower chance of the event at any given time (hazard ratio 0.76).
The absolute difference, how many more people out of 100 were helped, is not reported here.
Medians not reported in the abstract

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.

Overall survivalprimarysurvival endpoint

The treated group had about 12 percent lower chance of the event at any given time (hazard ratio 0.88).
The absolute difference, how many more people out of 100 were helped, is not reported here.

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Objective response rateresponse endpoint

32.8 vs 26.7 out of 100 had their tumour shrink with Neratinib + capecitabine compared with Lapatinib + capecitabine; 6.1 more per 100.
Roughly one extra person helped for every 16 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

The p-value (0.1201) 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.

Duration of responseother endpoint

Median 8.5 vs 5.6 months with Neratinib + capecitabine compared with Lapatinib + capecitabine; about 2.9 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 50 percent lower chance of the event at any given time (hazard ratio 0.5, likely range 0.33 to 0.74).

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

Intervention for CNS disease (cumulative incidence)other endpoint

22.8 vs 29.2 out of 100 reached this endpoint with Neratinib + capecitabine compared with Lapatinib + capecitabine; 6.4 fewer per 100.
On this measure the first group did worse, not better.

The p-value (0.043) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Diarrhoea (all grades)other endpoint

83 vs 66 out of 100 reached this endpoint with Neratinib + capecitabine compared with Lapatinib + capecitabine; 17 more per 100.
Roughly one extra person helped for every 6 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: HER2-positive metastatic breast cancer after two or more HER2-directed regimens: neratinib plus capecitabine against lapatinib plus capecitabine. People in a different situation may not see the same effect.
The trial selected people by a biomarker (HER2); the result should not be assumed for people whose cancer does not have it.

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.

621 enrolled.

Progression-free survival (central review)primary

HR 0.76 (0.63 to 0.93) · p = 0.0059

Medians not reported in the abstract

Source

Overall survivalprimary

HR 0.88 (0.72 to 1.07) · p = 0.2098

Numbers not yet public.

Source

Objective response rate

· p = 0.1201

Neratinib + capecitabine32.8 of 100

n = 307

Lapatinib + capecitabine26.7 of 100

n = 314

Download

Source

Duration of response

HR 0.5 (0.33 to 0.74) · p = 0.0004

Download

Source

Intervention for CNS disease (cumulative incidence)

· p = 0.043

Neratinib + capecitabine22.8 of 100

n = 307

Lapatinib + capecitabine29.2 of 100

n = 314

Download

Source

Diarrhoea (all grades)

Neratinib + capecitabine83 of 100

n = 307

Lapatinib + capecitabine66 of 100

n = 314

Download

Loperamide prophylaxis

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Progression-free survival (central review)primary	Neratinib + capecitabine	307	Medians not reported in the abstract	0.76 (0.63 to 0.93)	0.0059	link
Progression-free survival (central review)primary	Lapatinib + capecitabine	314	-	0.76 (0.63 to 0.93)	0.0059	link
Overall survivalprimary	Neratinib + capecitabine	307	-	0.88 (0.72 to 1.07)	0.2098	link
Overall survivalprimary	Lapatinib + capecitabine	314	-	0.88 (0.72 to 1.07)	0.2098	link
Objective response rate	Neratinib + capecitabine	307	32.8%	-	0.1201	link
Objective response rate	Lapatinib + capecitabine	314	26.7%	-	0.1201	link
Duration of response	Neratinib + capecitabine	307	8.5 months	0.5 (0.33 to 0.74)	0.0004	link
Duration of response	Lapatinib + capecitabine	314	5.6 months	0.5 (0.33 to 0.74)	0.0004	link
Intervention for CNS disease (cumulative incidence)	Neratinib + capecitabine	307	22.8%	-	0.043	link
Intervention for CNS disease (cumulative incidence)	Lapatinib + capecitabine	314	29.2%	-	0.043	link
Diarrhoea (all grades)	Neratinib + capecitabine	307	83%	-	-	link
Diarrhoea (all grades)	Lapatinib + capecitabine	314	66%	-	-	link

Taking part

NCT01808573completed

Run by: Puma Biotechnology, Inc.
Open to: 18 Years and over, any sex
Enrolment: 621
Sites: 252
Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Netherlands, Portugal, Russia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Registry updated: 2021-06-11

The full inclusion and exclusion criteria are on the registry record. Read 2026-10-07. Recruiting overall does not mean a particular site is open; ask the study team.

ClinicalTrials.gov data courtesy of the US National Library of Medicine.

Key papers

rctJournal of Clinical Oncology 2020476 citations

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

Connected

Trial
TUXEDO-1
Shares HER2-positive breast cancer with brain metastases, HER2-positive breast cancer, Breast cancer (all types) and the tag subtype-trials.
Trial
ATEMPT
Shares HER2-positive breast cancer, Breast cancer (all types) and the tag subtype-trials.
Trial
PATINA
Shares HER2-positive breast cancer, Breast cancer (all types) and the tag subtype-trials.
Trial
GeparSixto
Shares Lapatinib, Breast cancer (all types) and the tag subtype-trials.
Trial
BOLERO-2
Shares Breast cancer (all types), Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
HERACLES
Shares Lapatinib and the tag subtype-trials.
Trial
CARMENA
Shares Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
TAM-01
Shares Breast cancer (all types) and the tag subtype-trials.

cancers

Breast cancer (all types)HER2-positive breast cancer HER2-positive breast cancer with brain metastases

technologies

HER2 tyrosine kinase inhibitors Small-molecule kinase inhibitors

drugs

ApprovedOral fluoropyrimidine prodrug (antimetabolite)

Capecitabine · Xeloda

ApprovedSmall-molecule reversible HER2/EGFR kinase inhibitor

Lapatinib · Tykerb

ApprovedSmall-molecule irreversible pan-HER kinase inhibitor

Neratinib · Nerlynx

companies

Puma Biotechnology

people

Cristina Saura

key papers

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

Sources

Every source this page cites, grouped by who published it. Grouping is read from the web address, not assigned by hand.

ClinicalTrials.gov · 1

ClinicalTrials.gov NCT01808573

A source that has moved or gone is reported by the weekly link check. /audit/

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

Sourced, not expert-reviewed

NALA

Outcomes

Taking part

Key papers

Connected

Similar pages

cancers

technologies

drugs

companies

people

key papers

Sources

NALA

Outcomes

Taking part

Key papers

Connected

Similar pages

cancers

technologies

drugs

companies

people

key papers

Sources

NALA

Overview

Outcomes

Taking part

Key papers

Connected

Similar pages

cancers

technologies

drugs

companies

people

key papers

Sources

NALA

Overview

Outcomes

Taking part

Key papers

Connected

Similar pages

cancers

technologies

drugs

companies

people

key papers

Sources