Annals of Oncology: T-DM1 efficacy and safety in HER2-positive metastasis breast cancer and brain metastasis breast cancer patients.

HER2-positive brain metastasis breast cancer patients represent a class of incurable populations in which T-DM1 exhibits potential anti-tumor activity in small clinical studies.
there are studies that suggest that T-DM1 compared to Lapatini combined with carpentry can improve the total survival (OS) of patients with advanced metastatic breast cancer who have previously received radiation therapy.
2020, the Annals of Oncology published the results of T-DM1 in HER2-positive metastasis breast and brain metastasis breast cancer patients.
The study background HER2-positive breast cancer patients develop a high risk of developing central nervous system metastasis diseases, especially brain metastasis, poor prognostication in brain metastasis patients, HER2-positive metastasis breast cancer (MBC) and brain metastasis (BM) patients have limited treatment options, previous studies have shown that systemic treatment with HER2 targets may improve the prognostic prognostication of HER2-positive MBC and BM patients.
study of
-skin growth factor EGFR/HER2 targeted tyrosine kinase inhibitors (TKIs) Rapatinib and Lynatinib (single-drug or combined carpentabine) and HER2-specific TKIs Tucatinib reported anti-tumor activity in HER2-positive MPC and BM patients.
Among other potential anti-tumor-active drugs in these patients, studies have suggested that T-DM1 compared to Lapatinib combined with carpedabine can improve the late-stage MPC of clopidoju monoantitor resistance and OS in patients with symptoms of BM who have previously received radiotherapy.
two small additional studies also showed that T-DM1 had clinical anti-tumor activity in HER2-positive MBC and BM patients.
KAMILLA is an ongoing Phase III.b study of international one-arm open labels to assess the effectiveness and safety of T-DM1 in patients with HER2-positive advanced breast cancer who have been treated in the past.
analysis found that T-DM1 was well-to-do and had the same efficacy as previously reported.
the study, which reported results from KAMILLA queue 1 data, described the safety and effectiveness of T-DM1 in patients with baseline brain transfer and brainless metastasis.
study method KAMILLA Study Queue 1 is planned to reach 2,000 patients, preliminary findings have been reported, so far, Queue 2 has recruited 182 patients, including only patients in Asia, follow-up is ongoing.
eligible patients are those who have previously received HER2 targeted treatment and treatment after disease progression or advanced breast cancer treatment or disease progression within 6 months of completion of complementary treatment.
patients with untreated, symptomatic brain metastasis or 14 days of controlled brain transfer before entering the group are also eligible.
the patient to sign an informed consent.
subjects received T-DM1 3.6mg/kg every 3 weeks (intravenously) until insulable toxicity, withdrawal of informed consent, or progression of the disease.
the purpose of this study, The purpose of the exploratory analysis was to assess the clinical activity and safety of T-DM1 in the baseline BM patient subgroup.
main study endpoints are the optimal overall remission rate (BOR: Full Remission (CR) plus partial remission (PR) and clinical benefit rate (CBR: CR-PR plus Disease Stability (SD) duration of 6 months), as well as progression-free survival (PFS), OS, and safety.
results from November 12, 2012 to September 29, 2014 in a total of 2003 patients, 2002 patients received T-DM1 treatment, data as of January 31, 2017), the middle follow-up The time was 20.6 months, and in 398 patients treated, there was BM at baseline, and the demographic and disease characteristics of the two groups of patients with baseline presence and non-presence of BM were comparable;
BM patients when the baseline was used, the overall tumor response was evaluated according to RECIST 1.1 version.
of the 126 patients with baseline measurable brain metastasis, 3 patients reached CR, 24 reached PR, and BOR of all organs was 21.4% (27/126; 95% CI 14.6 to 29.6).
27 patients with SD duration of 6 months, CBR was 42.9% (54/126; 95% CI 34.1 to 52.0), and the maximum diameter of brain target lesions decreased by 30 The percentage of the population was 42.9% (54/126; 95% CI 34.1 to 52.0), including those rated as SD or disease progression (PD) based on the RECIST1.1 standard.
in 126 patients with measurable lesions, the maximum diameter of intracranial target lesions was reduced by 50% (5/10; 95% CI 18.7 to 81.3) 30 days before the baseline to receive brain radiotherapy, 32.7% (32.7% 16/49;95% CI 20.0 to 47.6) Patients received brain radiotherapy 30 days before the baseline, 49.3% (33/67; 95% CI 36.9 to 61.8) did not receive brain radiotherapy.
In 54 patients with a maximum diameter reduction of 30% of intracranial target lesions, 9 patients continued to use T-DM1 after CNS disease progression, with a medium duration of 9.5 months, and changes in target lesions in patients who received and did not receive radiotherapy.
overall population survival results showed that the baseline presence of BM and BM-free patients with the middle PFS was 5.5 months (95% CI 5.3 to 5.6 months) vs 7.7 months (95% CI 6.8 to 8.1 months) The medium OS was 18.9 months (95% CI 17.1 to 21.3 months) vs 30 months (95% CI 27.6 to 31.2 months), respectively, and the potential prognossion factors of OS were evaluated by the exploratory Cox model.
in a single-variable analysis, the presence of BM at baseline is associated with an OS decrease (estimated HR=1.68 (95% CI 1.46 to 1.93; P.0001).
in multivariable Cox analysis, in-brain lesions at baseline are still statistically significant variables.
, however, the estimated magnitude of the adjusted BM effect is small . . . the adjusted BM effect estimate is 1.18 (95% CI 1.02 to 1.38; P . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68) and found that several other variables may be associated with OS reduction, including older age, shorter time since diagnosis of metastasis disease, ECOG score of 1, presence of liver metastasis, the number of metastasis sites and the number of lines of past MPC treatment.
during T-DM1 treatment, a total of 269 patients developed new brain metastasis lesions, including 28.9 percent of baseline BM patients and 9.6 percent of baseline BM-free patients.
KAMILLA trial allowed for systematic disease control, new brain metastasis lesions continued to be used after surgery or radiotherapy, and the researchers reported that 69 patients continued to use T-DM1 after progression of brain metastasis lesions, 40 of which had BM in the baseline and 29 had no BM in the baseline.
of these patients, 67 patients were subsequently treated with T-DM1 (after progress) with a medium duration of 6.2 months after progress.
patients with BM in the baseline (n-39) had a duration of 8.8 months, and patients without BM at the baseline (n-28) had a duration of 6.2 months.
In terms of safety, the proportion of patients with any adverse reactions (AE) at baseline was 92.5%, the proportion of patients with severe AE was 28.4%, the proportion of patients with any AE without baseline BM was 93.1% and the proportion of patients with severe AE was 19.6%.
AE rates are similar at all levels of the BM subgroup.
, however, the rate of headache and vomiting was slightly higher in patients with baseline BM, while the rate of fever was higher in patients without baseline BM.
the risk of AEs in the central nervous system was more common in patients with baseline BM (n=208,52.3%) compared to patients without BM at baseline (n=701,43.7%).
discussion and conclusion KAMILLA study is the largest number of BM patients currently included in HER2-positive advanced breast cancer and T-DM1 treatment (n-398).
Patients who assessed the maximum diameter of the brain metastasis stove according to the RECIST standard reduced the maximum diameter by 42.9%, and patients with new brain transfer lesions during T-DM1 treatment continued to use T-DM1 after local treatment of the brain transfer cooker.
safety of T-DM1 is similar to that of patients with or without BM at baseline.
progress has been made in the treatment of HER2-positive MPC, treatment is limited for patients who also have BM.
exploratory analysis of this prospective clinical study of HER2-positive metastasis breast cancer and brain metastasis breast cancer showed that T-DM1 was well active and toyed in this group of people and should be further explored.
.