NCT00968968

Continued HER2 Suppression With Lapatinib Plus Trastuzumab Versus Trastuzumab Alone

Terminated Phase 3 Results posted Last updated 10 June 2019

What this trial tests

Phase 3 trial testing Lapatinib in Cancer in 37 participants. Terminated before completion.

Timeline

20 January 2010

Primary endpoint
21 February 2014

30 March 2018

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Masking	none
Primary purpose	treatment
Enrollment	37
Start date	20 January 2010
Primary completion	21 February 2014
Estimated completion	30 March 2018
Sites	116 locations across Canada, United States

Drugs / interventions tested

• Lapatinib (LAPATINIB) — full drug profile →
• Trastuzumab (trastuzumab) — full drug profile →

Conditions studied

• Cancer — all drugs for Cancer →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival Primary · Time from randomization until disease progression or death, approximately 4 years

Progression-free survival (PFS) with lapatinib plus trastuzumab versus trastuzumab alone. Progression-free survival (PFS) is defined as the time from randomization to the earliest date of disease progression (with radiological evidence) or death from any cause, or to last contact date up to 21Feb2014. Disease Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1), a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum diameters recorded since the treatment started (the sum must have an absolute increase from nad

Group	Value	95% CI
Lapatinib + Trastuzumab	25	2.5 – 30.3
Trastuzumab	2	1.9 – 6.4

Overall Survival Secondary · Time from randomization until death, approximately 4 years

Overall Survival is defined as the interval of time (in months) between the date of randomization and the date of death due to any cause.

Group	Value	95% CI
Lapatinib + Trastuzumab	NA	36.5 – NA
Trastuzumab	NA	24.5 – NA

Best Overall Response Secondary · approximately 4 years

The best overall response was the best response from the start of the treatment until disease progression/recurrence and was determined programmatically using investigators assessment of responses of target lesion, non-target lesion and new lesions based on RECIST v1.1. Complete Response (CR) = disappearance of all target lesion and non-target lesions if applicable, and no new lesion; Partial Response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions and non-target lesion was neither complete response nor progressive disease (Non-CR/Non-PD) or not evaluable (NE); SD = N

Complete response (CR)

Group	Value	95% CI
Lapatinib + Trastuzumab	0
Trastuzumab	0

Partial response (PR)

Group	Value	95% CI
Lapatinib + Trastuzumab	2
Trastuzumab	0

Stable disease (SD)

Group	Value	95% CI
Lapatinib + Trastuzumab	1
Trastuzumab	2

Non - CR/Non - PD

Group	Value	95% CI
Lapatinib + Trastuzumab	4
Trastuzumab	3

Progressive disease (PD)

Group	Value	95% CI
Lapatinib + Trastuzumab	1
Trastuzumab	7

Not evaluable (NE)

Group	Value	95% CI
Lapatinib + Trastuzumab	12
Trastuzumab	5

Clinical Benefit Response Rate (CR, PR or SD ≥24 Weeks) Secondary · approximately 4 years

Clinical Benefit Rate (CBR) was defined as the percentage of patients achieving either a confirmed CR or PR at any time or maintaining SD for at least 24 weeks while on study, according to the investigator assessment of response per RECIST 1.1 criteria. Confirmed CR - at least two determinations of CR at least 4 weeks apart before PD; Confirmed PR - at least two determinations of PR or better at least 4 weeks apart before PD.

Group	Value	95% CI
Lapatinib + Trastuzumab	10	1.2 – 31.7
Trastuzumab	0	NA – NA

Adverse Event Profile of the Two Treatment Arms Secondary · From first dose of study treatment until 30 days after the last dose of study treatment, approximately 8 years.

Any AEs

Group	Value	95% CI
Lapatinib + Trastuzumab	18
Trastuzumab	16

AEs related to study treatment

Group	Value	95% CI
Lapatinib + Trastuzumab	16
Trastuzumab	7

AEs leading to discont. of study treatment

Group	Value	95% CI
Lapatinib + Trastuzumab	3
Trastuzumab	0

AE leading to dose reduction

Group	Value	95% CI
Lapatinib + Trastuzumab	0
Trastuzumab	0

AE leading to dose interruption/delay

Group	Value	95% CI
Lapatinib + Trastuzumab	11
Trastuzumab	2

Any SAE

Group	Value	95% CI
Lapatinib + Trastuzumab	7
Trastuzumab	4

SAEs related to study treatment

Group	Value	95% CI
Lapatinib + Trastuzumab	3
Trastuzumab	1

Fatal SAEs

Group	Value	95% CI
Lapatinib + Trastuzumab	0
Trastuzumab	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 8.5 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lapatinib + Trastuzumab

Serious: 7/18 (39%)

Deaths: 0/18

Trastuzumab

Serious: 4/17 (24%)

Deaths: 0/17

All Subjects

Serious: 11/35 (31%)

Deaths: 0/35

Serious adverse events (16 terms)

Reaction	System	Lapatinib + Trastuzumab	Trastuzumab	All Subjects
Cellulitis	Infections and infestations	—	—	—
Pericardial effusion	Cardiac disorders	—	—	—
Goitre	Endocrine disorders	—	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—	—
Volvulus	Gastrointestinal disorders	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—
Appendicitis	Infections and infestations	—	—	—
Peritonsillar abscess	Infections and infestations	—	—	—
Tonsillitis	Infections and infestations	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Ejection fraction decreased	Investigations	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—

Other adverse events (189 terms — click to expand)

Reaction	System	Lapatinib + Trastuzumab	Trastuzumab	All Subjects
Diarrhoea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Pyrexia	General disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Sinusitis	Infections and infestations	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—
Nail disorder	Skin and subcutaneous tissue disorders	—	—	—
Hot flush	Vascular disorders	—	—	—
Vision blurred	Eye disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Seasonal allergy	Immune system disorders	—	—	—
Cellulitis	Infections and infestations	—	—	—
Localised infection	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Paraesthesia	Nervous system disorders	—	—	—

Most-reported serious reactions: Cellulitis, Pericardial effusion, Goitre, Pancreatitis acute, Volvulus, Cholecystitis acute, Cholelithiasis, Appendicitis.

Data from ClinicalTrials.gov NCT00968968 adverse events section.

Sponsor's own description

This was a randomized, open-label, multi-center Phase III study evaluating the efficacy and safety of lapatinib in combination with trastuzumab versus trastuzumab alone as continued HER2 suppression therapy in women with HER2-positive metastatic breast cancer (MBC). Eligible subjects should have completed 12 to 24 weeks of first- or second-line treatment with trastuzumab plus chemotherapy, experienced either complete disappearance of all metastatic lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions, and been indicated to continue to receive trastuzumab alone as maintenance therapy. Eligible subjects who entered the LPT112515 study on first-line treatment should not have known history of central nervous system (CNS) metastases; subjects who entered the study on second-line treatment should not have known history of CNS metastases or have stable (asymptomatic and off steroids ≥3 months) CNS metastases. The primary objective of this study was to compare progression-free survival (PFS) in subjects with HER2-positive MBC randomized to receive treatment with lapatinib plus trastuzumab versus those randomized to receive trastuzumab alone. The secondary objectives included overall survival, clinical benefit response rate (CR, PR or SD ≥24 weeks) and the qualitative and quantitative adverse event profile of the 2 treatment arms. It was estimated that 280 subjects (140 per group) would be required to observe 193 PFS events.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development.
   Singh JC, Jhaveri K, Esteva FJ. · · 2014 · cited 81× · PMID 25025958 · DOI 10.1038/bjc.2014.388
2. Human epidermal growth factor receptor family-targeted therapies in the treatment of HER2-overexpressing breast cancer.
   Eroglu Z, Tagawa T, Somlo G. · · 2014 · cited 44× · PMID 24436312 · DOI 10.1634/theoncologist.2013-0283
3. Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.
   Hurvitz SA, Kakkar R. · · 2012 · cited 18× · PMID 24367193 · DOI 10.2147/bctt.s29996
4. Clinical data mining reveals analgesic effects of lapatinib in cancer patients.
   Zhou S, Zheng F, Zhan CG. · · 2021 · cited 4× · PMID 33574423 · DOI 10.1038/s41598-021-82318-w
5. Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease.
   Ogawa L, Lindquist D. · · 2018 · cited 4× · PMID 30687062 · DOI 10.1159/000494264
6. Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer.
   Abunada A, Sirhan Z, Thyagarajan A, Sahu RP. · · 2023 · cited 3× · PMID 37275938 · DOI 10.5306/wjco.v14.i5.198