Entry Detail
| General information | |
| Database: | DB01063 |
| Objective: | Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study (Neo ALTTO) |
| Authors: | Roberto Salgado |
| Title: | TumorInfiltrating Lymphocytes and Associations With Pathological Complete Response and EventFree Survival in human epidermal growth factor receptor 2Positive EarlyStage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. |
| Journal: | JAMA Oncology |
| Year: | 2015 |
| PMID: | 26181252 |
| Trial Design | |
| Clinical Trial Id: | NCT00553358 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomised, multicentre, openlabel, phase III study. |
| Key Patients Feature: | have human epidermal growth factor receptor 2positive breast cancer, tumor size greater than 2 cm, adequate organ function, and adequate cardiac function. The ethics committee and relevant health authorities at each participating site approved the study prior to start of recruitment and all patients gave written informed consent, which also covered future biomarker research. |
| Biomarker: | human epidermal growth factor receptor 2Positive; Levels of TILs were examined for their associations with efficacy end points adjusted for prognostic clinicopathological factors including PIK3CA genotype |
| Biomark Analysis: | TumorInfiltrating Lymphocytes and Associations With Pathological Complete Response and EventFree Survival in human epidermal growth factor receptor 2Positive EarlyStage Breast Cancer Treated With Lapatinib and Trastuzumab |
| Control Group Info: | oral lapatinib (1500 mg/d), intravenous trastuzumab (4 mg/kg loading dose follotheyd by 2 mg/kg), or the combination of lapatinib (1000 mg/d) plus the same dose of trastuzumab for 6 weeks. After 6 weeks of receiving the antihuman epidermal growth factor receptor 2 agents, patients started weekly paclitaxel therapy (80 mg/m2) for a total of 12 weeks. Lapatinib doses were reduced during the paclitaxel administration |
| Treatment Info: | 455 women were randomized to 1 of 3 treatment groups: oral lapatinib (1500 mg/d), intravenous trastuzumab (4 mg/kg loading dose follotheyd by 2 mg/kg), or the combination of lapatinib (1000 mg/d) plus the same dose of trastuzumab for 6 weeks. After 6 weeks of receiving the antihuman epidermal growth factor receptor 2 agents, patients started weekly paclitaxel therapy (80 mg/m2) for a total of 12 weeks. Lapatinib doses were reduced during the paclitaxel administration. |
| Primary End Point: | pCR in the breast and lymph nodes |
| Secondary End Point: | EFS. |
| Patients Number: | 455 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23.4%]) and lapatinib plus trastuzumab (32 [21.1%]) than with trastuzumab (three [2.0%]). Similarly, grade 3 liverenzyme alterations were more frequent with lapatinib (27 [17.5%]) and lapatinib plus trastuzumab (15 [9.9%]) than with trastuzumab (11 [7.4%]). |
| Conclusions: | the concept that a group of patients with ¡°high¡± TIL levels can have an excellent outcome with the current standard of trastuzumab therapy alone with chemotherapy, although they acknowledge the difficulty of proposing such cutoffs for clinical implementation. If a TIL cutoff can be identified and robustly validated using the large adjuvant human epidermal growth factor receptor 2positive data sets, future clinical trials of antihuman epidermal growth factor receptor 2 therapy may be better placed to test the efficacy of new therapies in the poor prognostic group. |