Trial Outcomes & Findings for Lapatinib In Chemotherapy-Naive Or Metastatic Breast Cancer (NCT NCT00089999)

Last Updated: 2017-02-28

Results Overview

OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of \>= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

138 participants

Primary outcome timeframe

From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)

Results posted on

2017-02-28

Participant Flow

Participants (par.) with histologically confirmed invasive breast cancer with incurable stage IIIb, stage IIIc with T4 lesion, or stage IV disease at primary diagnosis or at relapse after curative-intent surgery and whose tumors overexpressed ErbB2 protein, documented by FISH were eligible for inclusion in this phase II study.

Participant milestones

Participant milestones
Measure	Lapatinib 1500 mg QD Participants received lapatinib 1500 milligram (mg) orally once daily (QD). Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID Participants received lapatinib 500 mg orally twice daily (BID). Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Overall Study STARTED	69	69
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	69	69

Reasons for withdrawal

Reasons for withdrawal
Measure	Lapatinib 1500 mg QD Participants received lapatinib 1500 milligram (mg) orally once daily (QD). Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID Participants received lapatinib 500 mg orally twice daily (BID). Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Overall Study Adverse Event	4	7
Overall Study Withdrawal by Subject	0	4
Overall Study Lost to Follow-up	2	1
Overall Study Radiological Progression of Cancer	52	44
Overall Study Symptomatic Progression of Cancer	2	5
Overall Study Death	3	3
Overall Study Poor General Condition	1	0
Overall Study Clinical Progression	1	2
Overall Study Physician Decision	2	2
Overall Study Patient Underwent Surgery	2	0
Overall Study Skin Nodule Over Right Mastectomy	0	1

Baseline Characteristics

Lapatinib In Chemotherapy-Naive Or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Total n=138 Participants Total of all reporting groups
Age, Continuous	53.2 Years STANDARD_DEVIATION 14.27 • n=5 Participants	53.4 Years STANDARD_DEVIATION 13.66 • n=7 Participants	53.3 Years STANDARD_DEVIATION 13.92 • n=5 Participants
Gender Female	69 Participants n=5 Participants	69 Participants n=7 Participants	138 Participants n=5 Participants
Gender Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Race/Ethnicity, Customized American Hispanic	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)

Population: Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of investigational product.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC) CR	0 Participants	0 Participants
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC) PR	15 Participants	18 Participants

PRIMARY outcome

Timeframe: From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)

Population: ITT Population

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator CR	1 Participants	2 Participants
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator PR	16 Participants	20 Participants

SECONDARY outcome

Timeframe: From the date of the first dose of investigational product until the date of disease progression or death due to breast cancer (up to Study Week 103)

Population: ITT Population

Clinical benefit is defined as the numer of participants achieving either a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD,or complete resolution of TLs and the persistence of one or more non-TLs)or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of 1 or more new TLs or non-TLs and/or unequivocal progressionn of existing non-target lesions\], taking as reference, the smallest sum LD since the treatment started) for at least 24 weeks. This was based on confirmed responses from the investigator assessment of clinical benefit.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD] for at Least 24 Weeks), as Assessed by the IRC and Investigator IRC	29.0 Percentage of Participants	33.3 Percentage of Participants
Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD] for at Least 24 Weeks), as Assessed by the IRC and Investigator Investigator	29.0 Percentage of Participants	40.6 Percentage of Participants

SECONDARY outcome

Timeframe: From the date of the first dose of investigational product until the first documented evidence of a PR or CR (up to Study Week 103)

Population: ITT Population. Only those participants with CR or PR were analyzed (represented by n=X in the category titles). Different participants may have been analyzed by the IRC and the Investigator, so the overall number of participants analyzed reflects everyone in the ITT Population.

Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Time to Response, as Assessed by the IRC and Investigator IRC, n=15, 18	7.9 Weeks Interval 7.0 to 12.0	7.9 Weeks Interval 7.0 to 20.0
Time to Response, as Assessed by the IRC and Investigator Investigator, n=17, 22	8.0 Weeks Interval 7.0 to 19.0	8.0 Weeks Interval 5.0 to 46.0

SECONDARY outcome

Timeframe: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Study Week 103)

DoR is defined for the subset of par. who had a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of \>= 1 non-TL\[s\]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of \>= 1 new lesions or unequivocal progression of existing non-TLs. For par. who did not progress or die, DoR was censored on the date of the last radiological scan. If a par.had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Duration of Response (DoR), as Assessed by the IRC and Investigator IRC,n=15, 18	27.6 Weeks Interval 20.1 to 39.4	29.0 Weeks Interval 20.3 to The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate it.
Duration of Response (DoR), as Assessed by the IRC and Investigator Investigator, n=17, 22	27.6 Weeks Interval 15.4 to 39.4	29.0 Weeks Interval 15.7 to 36.1

SECONDARY outcome

Timeframe: From the date of the first dose of investigational product until the earlier of the date of disease progression or death due to any cause (up to Study Week 103)

Population: ITT Population

Progression-free survival is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Disease progression was based on the IRC's and investigator's assessments of the objective evidence (e.g., radiological scans and medical photographs). For participants who did not progress, or die, progression-free survival was censored at the time of the last IRC assessed radiological scan.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Progression-free Survival, as Assessed by the IRC and Investigator IRC	19.6 Weeks Interval 16.4 to 28.1	24.4 Weeks Interval 19.7 to 35.9
Progression-free Survival, as Assessed by the IRC and Investigator Investigator	17.6 Weeks Interval 12.1 to 20.0	20.3 Weeks Interval 13.3 to 24.4

SECONDARY outcome

Timeframe: From randomization until the first documented sign of disease progression, death due to any cause, or early discontinuation from investigational product (up to Study Week 103)

Population: ITT Population

Time to treatment failure is calculated as the interval between the date of randomization and the occurrence of local tumor progression (including ipsilateral \[on the same side\] and controlateral breast tumor progression), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional treatment arm), or death due any cause. For participants who did not progress, die or discontinue early, time to treatment failure was censored at the last scan date.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Time to Treatment Failure, as Assessed by IRC and Investigator Investigator	12.3 Weeks Interval 10.0 to 19.6	16.1 Weeks Interval 12.3 to 23.1
Time to Treatment Failure, as Assessed by IRC and Investigator IRC	15.7 Weeks Interval 11.6 to 19.3	17.0 Weeks Interval 13.1 to 20.3

SECONDARY outcome

Timeframe: From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to study week 192)

Population: Safety Population: all randomized participants who received at least one dose of investigational product.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs.

Outcome measures

Outcome measures
Measure	Lapatinib 1500 mg QD n=69 Participants Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.	Lapatinib 500 mg BID n=69 Participants Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any AE	65 Participants	61 Participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any SAE	15 Participants	18 Participants

Adverse Events

Lapatinib 1500 mg QD

Serious events: 15 serious events

Other events: 58 other events

Deaths: 0 deaths

Lapatinib 500 mg BID

Serious events: 18 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER