Trial Outcomes & Findings for Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer (NCT NCT01622868)

Last Updated: 2023-10-17

Results Overview

The Response Evaluation Criteria in Solid Tumors (RECIST) criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

143 participants

Primary outcome timeframe

Baseline and 12 weeks post RT (approximately 12 weeks from start of treatment if SRS and 15 if WBRT)

Results posted on

2023-10-17

Participant Flow

Participant milestones

Participant milestones
Measure	Radiation Therapy Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Overall Study STARTED	72	71
Overall Study Eligible	65	71
Overall Study Eligible, Started Study Treatment, Has Adverse Event Data	63	71
Overall Study COMPLETED	65	71
Overall Study NOT COMPLETED	7	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Radiation Therapy Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Overall Study Protocol Violation	7	0

Baseline Characteristics

Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiation Therapy n=65 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=71 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))	Total n=136 Participants Total of all reporting groups
Age, Customized < 50 years	22 Participants n=65 Participants	25 Participants n=71 Participants	47 Participants n=136 Participants
Age, Customized ≥ 50 years	43 Participants n=65 Participants	46 Participants n=71 Participants	89 Participants n=136 Participants
Sex: Female, Male Female	65 Participants n=65 Participants	71 Participants n=71 Participants	136 Participants n=136 Participants
Sex: Female, Male Male	0 Participants n=65 Participants	0 Participants n=71 Participants	0 Participants n=136 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=65 Participants	3 Participants n=71 Participants	11 Participants n=136 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants n=65 Participants	67 Participants n=71 Participants	124 Participants n=136 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=65 Participants	1 Participants n=71 Participants	1 Participants n=136 Participants
Karnofsky Performance Status 60	9 Participants n=65 Participants	2 Participants n=71 Participants	11 Participants n=136 Participants
Karnofsky Performance Status 70-80	29 Participants n=65 Participants	27 Participants n=71 Participants	56 Participants n=136 Participants
Karnofsky Performance Status 90-100	27 Participants n=65 Participants	42 Participants n=71 Participants	69 Participants n=136 Participants
Graded Prognostic Assessment for Breast Cancer (Breast-GPA) 1.5-2.0	5 Participants n=65 Participants	4 Participants n=71 Participants	9 Participants n=136 Participants
Graded Prognostic Assessment for Breast Cancer (Breast-GPA) 2.5-3.0	35 Participants n=65 Participants	37 Participants n=71 Participants	72 Participants n=136 Participants
Graded Prognostic Assessment for Breast Cancer (Breast-GPA) 3.5-4.0	25 Participants n=65 Participants	30 Participants n=71 Participants	55 Participants n=136 Participants
Use of Non-central nervous system (CNS) penetrating HER2 Blockade at Study Entry No (None)	23 Participants n=65 Participants	28 Participants n=71 Participants	51 Participants n=136 Participants
Use of Non-central nervous system (CNS) penetrating HER2 Blockade at Study Entry Yes (Trastuzumab and/or Pertuzumab)	42 Participants n=65 Participants	43 Participants n=71 Participants	85 Participants n=136 Participants
Previous Stereotactic SRS or Surgery No	37 Participants n=42 Participants • Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.	41 Participants n=47 Participants • Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.	78 Participants n=89 Participants • Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.
Previous Stereotactic SRS or Surgery Yes	5 Participants n=42 Participants • Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.	6 Participants n=47 Participants • Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.	11 Participants n=89 Participants • Eligible participants randomized before the October 2016 protocol amendment which removed this stratification factor.
Planned RT SRS	6 Participants n=65 Participants	6 Participants n=71 Participants	12 Participants n=136 Participants
Planned RT WBRT	59 Participants n=65 Participants	65 Participants n=71 Participants	124 Participants n=136 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks post RT (approximately 12 weeks from start of treatment if SRS and 15 if WBRT)

Population: Evaluable data for determining the 12-week post-RT RECIST response was available for 52 eligible participants on the RT alone arm and 64 on the lapatinib arm.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=52 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=64 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Complete Response (CR) Rate in the Brain at 12 Weeks Post-radiation Therapy (RT) Using the RECIST 1.1 Criteria Based on Brain Magnetic Resonance Imaging (MRI)	5.8 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 4 weeks post RT (approximately 4 weeks from start of treatment if SRS and 7 if WBRT)

Population: Evaluable data for determining the 4-week post-RT RECIST response was available for 55 eligible participants on the RT alone arm and 67 on the lapatinib arm.

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=55 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=67 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Complete Response Rate in the Brain at 4 Weeks Post-RT Using the RECIST 1.1 Criteria Based on Brain MRI	3.6 percentage of participants	1.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

Population: Evaluable data for determining the 4- and 12-week post-RT WHO response was available for 55 eligible participants at week 4 and 52 at week 12 on the RT alone arm and 67 at week 4 and 64 at week 12 on the lapatinib arm.

The WHO/modified McDonald Criteria evaluates changes in bidimensional tumor measurements. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=65 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=71 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Complete Response Rate in the Brain Using the World Health Organization (WHO)/Modified McDonald Criteria Based on Brain MRI 4 weeks post-RT	3.6 percentage of participants	1.5 percentage of participants
Complete Response Rate in the Brain Using the World Health Organization (WHO)/Modified McDonald Criteria Based on Brain MRI 12 weeks post-RT	5.8 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

Population: Evaluable data for determining the 4- and 12-week post-RT RECIST response was available for 55 eligible participants at week 4 and 52 at week 12 on the RT alone arm and 67 at week 4 and 64 at week 12 on the lapatinib arm.

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Objective response is defined as a complete or partial response. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Partial response is defined as ≥ 30% reduction in the sum of diameters of up to 2 of the largest target lesions. Rate is calculated by dividing the number of patients with objective response by the number of analyzable patients.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=65 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=71 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Objective Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI 4 weeks post-RT	41.8 percentage of participants	55.2 percentage of participants
Objective Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI 12 weeks post-RT	59.6 percentage of participants	46.9 percentage of participants

SECONDARY outcome

Timeframe: From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.

Population: MRI scans were available for central review for progression outside targeted measurable disease for 41 eligible participants on the RT alone arm and 57 on the lapatinib arm.

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. CNS progressive disease outside the targeted measureable disease was determined by a retrospective central review of MRI scans by the study neuroradiology co-chair and is defined as the first occurrence since baseline of new lesions or progression of non-target lesions. Time to CNS progressive disease is defined as time from randomization to the date of progressive disease, last known follow-up (censored), or death (competing risk). Progression rates are estimated using the cumulative incidence method. One-year rates are provided.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=41 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=57 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Percentage of Participants With Progression in the Brain Outside the Targeted Measurable Disease Using the RECIST 1.1 Criteria Based on Brain MRI	22.0 percentage of participants Interval 10.7 to 35.7	37.7 percentage of participants Interval 25.0 to 50.3

SECONDARY outcome

Timeframe: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

Population: Evaluable data for determining the 4- and 12-week post-RT RECIST target lesion measurement response was available for 51 eligible participants at week 4 and 43 at week 12 on the RT alone arm and 66 at week 4 and 57 at week 12 on the lapatinib arm.

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Objective response is defined as a complete or partial response. Complete response is defined as the complete disappearance of all enhancing disease and partial response is defined as ≥ 30% reduction in the diameter of the target lesion. Lesions were evaluated individually. Rate is calculated by dividing the number of lesions with objective response by the number of analyzable lesions.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=90 lesions Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=116 lesions 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Targeted Lesion-specific Objective Response Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI 4 weeks post-RT	51.1 percentage of lesions	56.0 percentage of lesions
Targeted Lesion-specific Objective Response Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI 12 weeks post-RT	75.0 percentage of lesions	61.4 percentage of lesions

SECONDARY outcome

Timeframe: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Progression is defined as ≥ 20% increase in the diameter of the target lesion relative to nadir. Lesions were evaluated individually. Rate is calculated by dividing the number of lesions with progression by the number of analyzable lesions.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=90 lesions Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=116 lesions 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Targeted Lesion-specific Progression Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI 4 weeks post-RT	3.3 percentage of lesions	1.7 percentage of lesions
Targeted Lesion-specific Progression Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI 12 weeks post-RT	6.6 percentage of lesions	14.9 percentage of lesions

SECONDARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.

Population: Eligible participants who started study treatment and have adverse event data.

Adverse events reported as definitely, probably, or possibly related to protocol treatment. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data provided in this outcome measure. See Adverse Events Module for specific Adverse Event data.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=63 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=71 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Frequency of Highest Treatment-related Adverse Event Per Participant Grade 1	8 Participants	14 Participants
Frequency of Highest Treatment-related Adverse Event Per Participant Grade 2	23 Participants	20 Participants
Frequency of Highest Treatment-related Adverse Event Per Participant Grade 3	5 Participants	20 Participants
Frequency of Highest Treatment-related Adverse Event Per Participant Grade 4	0 Participants	4 Participants
Frequency of Highest Treatment-related Adverse Event Per Participant Grade 5	0 Participants	0 Participants

SECONDARY outcome

Population: Evaluable data for determining overall post-RT RECIST response was available for 54 eligible participants on the RT alone arm and 68 on the lapatinib arm.

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Overall complete response is defined as the complete disappearance of all CNS target lesions sustained for at least 4 weeks; with no new lesions, no use of corticosteroids, and patient is stable or improved clinically. All site-reported MRI data and all site-reporting of clinical progressive disease indicators were used in this analysis. Rate is calculated by dividing the number of participants with overall complete response by the number of analyzable participants.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=54 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=68 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Overall Complete Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	0 Participants	0 Participants

SECONDARY outcome

Population: Evaluable data for determining overall post-RT RECIST response was available for 54 eligible participants on the RT alone arm and 68 on the lapatinib arm.

The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Overall progression is defined as unequivocal progression, new or worsening tumor-related neurological symptoms, tumor-related increase in steroid dose, new primary in brain, or progression in target lesions. All site-reported MRI data and all site-reporting of clinical progressive disease indicators were used in this analysis. Rate is calculated by dividing the number of participants with progression by the number of analyzable participants.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=54 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=68 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Overall Progression Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	38 Participants	54 Participants

SECONDARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.

Population: Eligible participants

An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 101 deaths were reported.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=65 Participants Stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT)	Lapatinib and Radiation Therapy n=71 Participants 1000 mg Lapatinib for six weeks with radiation therapy (stereotactic radiosurgery (SRS) or 3 weeks of whole brain radiotherapy (WBRT))
Overall Survival (OS)	15.6 months Interval 8.4 to 19.1	15.3 months Interval 12.3 to 21.0

Adverse Events

Radiation Therapy

Serious events: 17 serious events

Other events: 49 other events

Deaths: 48 deaths

Lapatinib and Radiation Therapy

Serious events: 16 serious events

Other events: 63 other events

Deaths: 53 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 215-574-3208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior approval from the sponsor. In addition, PI's are required to abide by the collaborator's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER