Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication TYKERB ® is indicated in combination with: capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress human epidermal growth factor receptor 2 (HER2) and who have received prior therapy, including an anthracycline, a taxane, and trastuzumab. FDA label
Also known as Lapatinib (GW572016) oral tablets, Tyverb, Tykerb, GW572016
lapatinib · 13 trials · 5 indications
The Number of Participants with Progression free survival (PFS) events in the Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) arm vs. Trastuzumab + Aromatase Inhibitor (AI) arm was based on assessments by the Investigator.
Progression free survival (PFS) was defined as the interval of time between the date of randomization and the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor. Disease progression was based on assessments by the Investigator.
Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Pathological complete response is defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to National Surgical Adjuvant Breast and Bowel Project (NSABP) guidelines, which do not take into account the histological nodal status.
Disease-Free Survival (DFS) was defined as the interval between randomization and the date of first occurrence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer or death without recurrence. Only deaths occurring in participants whose clinical follow-up was ongoing at the time of death and who had no recurrence, contralateral breast cancer (CBC) or second primary malignancy (SPM) reported prior to death were considered as death without recurrence. DFS was estimated using the Kaplan Meier method. The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who had disease free survival for the indicated years.
Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause.
PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. The date of documented PD is defined as the date of radiological PD as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0), PD is defined as a 20% increase in the sum of the longest diameter (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 lesions.
PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as 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 lesions.
Comparison between the PAM50 HER2-E versus non HER2-E cases to achieve pCRB from dual HER2 blockade with lapatinib and trastuzumab at the time of surgery
PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. PD is defined as at least a 20 % increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of \>=1 new lesion.
OR was defined as the percentage of participants experiencing either a confirmed complete response (CR) or a confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0. CR is defined as the disappearance of all lesions (target and/or non-target). PR is defined as at least a 30% decrease in the sum of the longest dimensions (LD) of target lesions taking as a reference the baseline sum LD, with non-target lesions not increased or absent.
The PFS rate is defined as the percentage of subjects who have shown no evidence of disease progression or death from any cause following 12 weeks of treatment. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Since there is no independent reviewer, only the investigator response was reported.
Summary of CNS Objective Response (Lapatinib Monotherapy - MITT Population) Response to lapatinib in patients with progressive brain metastases from ErbB2-overexpressing breast cancer. The primary indicator of drug efficacy was CNS objective response rate. A CNS objective response was defined as either a Complete response (CR) or Partial response (PR), as assessed by volumetric analysis of brain Magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of Neurological signs and symptoms (NSS) A CNS objective response rate was defined as a 50% volumetric reduction in sum of CNS target lesions, with no new or progressive CNS or non-CNS lesions, no increases in tumor-related steroid requirements and no worsening of neurological signs or symptoms
Summary of CNS Objective Response (the Complete Response + Partial Response)
* The OTR for Treatment Group A (lapatinib, paclitaxel, carboplatin, and trastuzumab) will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle. * The OTR for Treatment Group B (lapatinib, paclitaxel, carboplatin) will be defined as the maximum dose level at which no more than one subject out of six experiences a DLT after completing one treatment cycle. * Adverse events and changes from baseline in laboratory values, Multiple-gated Acquisition (MUGA) scanning/Echocardiogram (ECHO), and vital signs will be evaluated to assess safety and tolerability.
| Arm | Type | Description |
|---|---|---|
| Treatment group A | EXPERIMENTAL | Lapatinib 1000 mg PO once daily + Trastuzumab (loading dose of 8 mg/kg) followed by the maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. |
| Treatment group B | ACTIVE_COMPARATOR | Trastuzumab (loading dose of 8 mg/kg) followed by maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. |
| Treatment Group C | ACTIVE_COMPARATOR | Lapatinib 1500 mg PO once daily + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. |
| CapeOx plus Lapatinib | EXPERIMENTAL | CapeOx plus Lapatinib |
| CapeOx plus Placebo | PLACEBO_COMPARATOR | CapeOx plus Placebo |
| Arm 1 Lapatinib | EXPERIMENTAL | 1500 mg lapatinib for 6 weeks followed by lapatinib plus weekly paclitaxel for an additional 12 weeks. After definitive surgery, 3 cycles of adjuvant FEC followed by 34 weeks of adjuvant lapatinib. |
| Arm 2 Trastuzumab | ACTIVE_COMPARATOR | 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly trastuzumab for 6 weeks followed by 2 mg/kg trastuzumab plus weekly paclitaxel for an additional 12 weeks. After definitive surgery, 3 cycles of adjuvant FEC followed by 34 weeks of adjuvant trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks). |
| Arm 3 Lapatinib plus Trastuzumab | EXPERIMENTAL | 1000 mg lapatinib plus 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly trastuzumab for 6 weeks, followed by 750 mg lapatinib plus 2 mg/kg IV weekly trastuzumab plus weekly paclitaxel for an additional 12 weeks. After definitive surgery, 3 cycles of adjuvant FEC followed by 34 weeks of adjuvant lapatinib (1000 mg) in combination with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks). |
| Lapatinib plus Trastuzumab | EXPERIMENTAL | Design 1: Oral lapatinib 1000 mg daily concurrent with trastuzumab 8 mg/kg IV loading dose followed by 6mg/kg IV every 3 weeks (52 weeks total). Design 2: Trastuzumab (4mg/kg loading dose followed by 2mg/kg IV weekly) concurrent with oral lapatinib 750 mg daily and either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 every 21 days for 4 cycles (12 weeks). After completion of chemotherapy, the dose of lapatinib will be increased to 1000mg daily concurrently with trastuzumab every 3 weeks (6mg/kg without loading dose) for an additional 40 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concurrently with oral lapatinib 750mg plus weekly trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV. After the completion of chemotherapy, trastuzumab will be administered every 3 weeks (6mg/kg without loading dose) concurrent with lapatinib 1000mg daily for an additional 40 weeks (52 weeks total). |
| Trastuzumab followed by Lapatinib | EXPERIMENTAL | Design 1: Trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV weekly) for 12 weeks followed by a 6 week treatment-free interval followed by oral lapatinib 1500mg daily for 34 weeks (52 weeks total). Design 2: Trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV weekly) for 12 weeks administered concomitantly and either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 every 21 days for 4 cycles; followed by a 6 week treatment-free interval followed by oral lapatinib 1500mg daily for 34 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concomitantly with trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV weekly) followed by a 6 week treatment-free interval followed by oral lapatinib 1500 mg daily for 28 weeks (52 weeks total). |
| Lapatinib | EXPERIMENTAL | Design 1: Lapatinib 1500mg oral daily for a total of 52 weeks. Design 2: Either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 IV every 3 weeks for 4 cycles administered concomitantly with oral lapatinib at 750mg daily. After completion of chemotherapy, oral lapatinib administered at 1500mg daily for an additional 40 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concomitantly with oral lapatinib at 750mg daily. After completion of chemotherapy, the dose of lapatinib will be increased to 1500mg oral daily for an additional 40 weeks (52 weeks total). |
| Trastuzumab | ACTIVE_COMPARATOR | Design 1: Trastuzumab 8mg/kg IV loading dose followed by 6mg/kg IV every 3 weeks for a total of 52 weeks. Design 2: Either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 IV every 3 weeks for 4 cycles administered concomitantly with trastuzumab 4mg/kg IV loading dose followed by 2mg/kg IV weekly. After completion of chemotherapy, trastuzumab administered every 3 weeks (6mg/kg IV without loading dose) for an additional 40 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concomitantly with trastuzumab 4mg/kg IV loading dose followed by 2mg/kg IV weekly. After completion of chemotherapy, trastuzumab (6mg/kg without loading dose) every 3 weeks for an additional 40 weeks (52 weeks total). |
| Paclitaxel and Lapatinib (Blinded) | EXPERIMENTAL | Paclitaxel and Lapatinib (Blinded) |
| Paclitaxel and Placebo (Blinded) | ACTIVE_COMPARATOR | Paclitaxel and Placebo (Blinded) |
| Open Label - Monotherapy (Extension Phase) | OTHER | Open Label - Monotherapy (Lapatinib) |
| Open Label - Combination Therapy (Extension Phase) | OTHER | Open Label - Combination Therapy (Lapatinib and Paclitaxel) |
| Placebo + Letrozole 2.5 mg | PLACEBO_COMPARATOR | Letrozole (2.5 mg once daily orally) with Placebo (which matched with Lapatinib tablet) |
| Lapatinib 1500 mg + Letrozole 2.5 mg | EXPERIMENTAL | Lapatinib (1500 mg once daily orally) with Letrozole (2.5 mg once daily orally) |
| Dual HER2 blockade | EXPERIMENTAL | For a total of 18 weeks, HR-negative patients will be given dual blockade consisting of daily lapatinib at 1000 mg and trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. |
| Dual HER2 blockade plus endocrine therapy | EXPERIMENTAL | For a total of 18 weeks, HR-positive patients will be given letrozole (2.5 mg daily) or tamoxifen (20 mg daily) with concurrent dual blockade consisting of daily lapatinib at 1000 mg and trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. |
| Lapatinib + Vinorelbine | EXPERIMENTAL | Lapatinib + Vinorelbine |
| Lapatinib + Capecitabine | ACTIVE_COMPARATOR | Lapatinib + Capecitabine |
| Single Arm | EXPERIMENTAL | Single arm combination therapy of Lap and NabPaclitaxel combination |
| Oral lapatinib tablets in combination with IV bevacizumab | EXPERIMENTAL | 1500 mg oral lapatinib (once daily) plus 10 mg/kg intravenous bevacizumab (every two weeks) |
| Group 1 | EXPERIMENTAL | Study Drug |
| Group 2 | EXPERIMENTAL | Study Drug |
| Group A | ACTIVE_COMPARATOR | Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes. Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion. Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15). Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks. |
| Group B | ACTIVE_COMPARATOR | Subjects in Treatment Group B (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by a ≥15 minute intravenous infusion of carboplatin. Doses of paclitaxel, and carboplatin will be administered weekly (Day 1, 8, and 15) for three weeks with cycles repeated every four weeks. |
| Name | Type | Description |
|---|---|---|
| Lapatinib | DRUG | 1000 mg by mouth once a day |
| Trastuzumab | DRUG | Loading dose of 8 mg/kg IV followed by the maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) |
| Aromatase Inhibitor | DRUG | Aromatase inhibitor (either letrozole, anastrozole, or exemestane) of investigator's choice given by mouth once daily |
| Placebo | DRUG | 5 pills once daily |
| Capecitabine | DRUG | 1700mg/m2/day in two daily doses |
| Oxaliplatin | DRUG | 130mg/m2 on day 1 |
| Paclitaxel | DRUG | antimicrotubule agent |
| Lapatinib (GW572016) oral tablets | DRUG | 1500 mg oral daily continuously |
| Paclitaxel infusion | DRUG | Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months |
| Letrozole | DRUG | 2.5 mg orally once a day |
| Endocrine Therapy | DRUG | Letrozole or tamoxifen will be prescribed according to patient's menopausal status |
| Vinorelbine | DRUG | Vinorelbine |
| Lapatinib/nab-Paclitaxel | DRUG | This was an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib (TYKERB) in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Subjects were to receive nab-paclitaxel (100 mg/m2 intravenously on Day 1, 8, 15, every 28 days (q28) days plus lapatinib (1000 mg once daily on a continuous basis). |
| bevacizumab | DRUG | 10 mg/kg intravenous bevacizumab (every two weeks) |
| Lapatinib in combination with an anti-cancer agent | DRUG | Lapatinib in combination with paclitaxel, letrozole, capecitabine, capecitabine/oxaliplatin, gemcitabine, docetaxel, trastuzumab, FOLFOX4, or FOLFIRI |
| Lapatinib in combination with an anti-cancer agent as specified by parent protocol | DRUG | Lapatinib in combination with an anti-cancer agent as specified by parent protocol |
| carboplatin | DRUG | An alkylating agent used in the treatment of some cancers |
Inclusion Criteria Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Signed written informed consent. In Korea and Japan, subjects between \>=18 and \<20 years of age must also have a legal representative sign the written informed consent. 2. Post-menopausal...
Lapatinib is studied for the treatment of breast cancer, breast neoplasms, cancer, neoplasms, and tumors of the gastrointestinal tract. It is an oral small molecule given as monotherapy or in combination with other anti-cancer agents, including capecitabine and nab-paclitaxel, in biomarker-selected patient populations.
Lapatinib targets EGFR and ERBB2, both members of the human epidermal growth factor receptor family. It acts as an inhibitor of these receptor tyrosine kinases. By blocking EGFR and ERBB2 signaling, lapatinib is designed to interfere with pathways that drive tumor cell growth in HER2-positive and EGFR-driven cancers.
Lapatinib is developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor associated with the clinical development program for this oral small molecule across its studied oncology indications.
Lapatinib is in Phase 2 development. It is an investigational agent and is not described as approved. Ten clinical trials have been completed, with no active trials currently listed, and the program has enrolled approximately 11,820 participants across its studies.
Completed lapatinib trials include NCT01973660, a Phase 2 study of the PAM50 HER2-enriched phenotype as a predictor of response to dual HER2 blockade in HER2-positive early breast cancer, and NCT01160211, a Phase 3 study comparing an aromatase inhibitor with lapatinib, trastuzumab, or both in hormone receptor positive, HER2-positive metastatic breast cancer.