Triple negative breast cancer (TNBC) breakthrough! Keytruda combined with neoadjuvant / adjuvant chemotherapy significantly improved the pathological remission of early TNBC!

October 8, 2019 / bioun / -- cancer immunotherapy giant Merck & Co recently announced the positive results of keytruda (pembrolizumab, pabolizumab) as a key new adjuvant / adjuvant phase III clinical research keynote-522 (nct03036488) in the treatment of early triple negative breast cancer (TNBC) patients It is worth mentioning that this study is the first randomized study to evaluate the new adjuvant / adjuvant treatment of TNBC with an anti-PD-1 therapy The results of the interim analysis were first published at the annual meeting of the European Society of Oncology (ESMO) in 2019 Previously, the US FDA has granted keytruda + chemotherapy breakthrough drug qualification (BTD) for new adjuvant treatment of high-risk early TNBC patients The BTD is based on data from the IB phase keynote-173 study and the II phase ispy2 study, which confirmed the exciting antitumor activity of neoadjuvant keytruda + chemotherapy in these patients Keynote-522, a randomized, double-blind phase III study, is investigating keytruda plus placebo as neoadjuvant therapy, followed by keytruda plus placebo as adjuvant therapy for TNBC patients The two main end points of the study were pathological complete remission (PCR) and event-free survival (EFS), based on a pre-determined group sequential approach PCR was defined as ypt0 / tis ypn0 (i.e., there was no invasive residual cancer in the breast and lymph nodes) Secondary endpoints included the use of other definitions of PCR (for example, ypt0 ypn0 - no invasive or non invasive residual cancer in the breast or lymph nodes during radical surgery, ypt0 / tis - no invasive residual cancer in the breast during radical surgery), total survival (OS), and safety of PCR, EFS, and OS in patients with tumor expression of PD-L1 (combined positive score [CPS] ≥ 1%) In this study, 1174 patients were randomly treated with keytruda (once every three weeks) + paclitaxel (once a week) and carboplatin (once a week or once every three weeks) for four cycles, followed by keytruda + cyclophosphamide and amomycin or epirubicin (once every three weeks) for four cycles as new adjuvant treatment before operation, Keytruda (once every three weeks) was used as adjuvant therapy for 9 cycles (2) Chemotherapy placebo regimen: placebo (once every three weeks) + paclitaxel (once a week) and carboplatin (once a week or once every three weeks) for four cycles, followed by placebo + cyclophosphamide and Adriamycin or epirubicin (once every three weeks) for four cycles, and then placebo (once every three weeks) as adjuvant therapy for nine cycles after operation The results of mid-term analysis showed that in neoadjuvant therapy, keytruda + chemotherapy (n = 401) showed a statistically significant increase in PCR (PCR: 64.8% vs 51.2%, P = 0.00055) compared with chemotherapy (n = 201) regardless of PD-L1 expression At another primary end point, EFS, a median follow-up of 15.5 months, keytruda showed a favorable trend in EFS, reducing the risk of progression and recurrence of neoadjuvant disease by 37% (HR = 0.63 [95% CI: 0.43-0.93]), compared with chemotherapy placebo In this study, the safety of keytruda and chemotherapy was consistent with previous studies In terms of the secondary end point of PCR defined by other definitions, the PCR rate defined by ypt0 ypn0, neoadjuvant keytruda + chemotherapy and neoadjuvant chemotherapy were 59.9% and 45.3%, respectively; the PCR rate defined by ypt0 / tis, neoadjuvant keytruda + chemotherapy and neoadjuvant chemotherapy were 68.6% and 53.7%, respectively In the exploratory subgroup analysis of PCR based on PD-L1 expression, keytruda in neoadjuvant chemotherapy showed improvement regardless of PD-L1 expression In the PD-L1 CPS ≥ 1 subgroup, the PCR rate of neoadjuvant keytruda + chemotherapy (n = 334) was 68.9%, and that of neoadjuvant chemotherapy (n = 164) was 54.9% In the PD-L1 CPS < 1 subgroup, the PCR rate of neoadjuvant keytruda + chemotherapy (n = 64) was 45.3%, and that of neoadjuvant chemotherapy (n = 33) was 30.3% In neoadjuvant stage, 99.0% of keytruda + chemotherapy patients (n = 781) and 99.7% of chemotherapy patients (n = 389) had treatment-related adverse events (teaes) of any level In the auxiliary period, 48.1% of keytruda + chemotherapy patients (n = 547) and 43.0% of chemotherapy patients (n = 314) had treatment-related adverse events (tea) of any level In the neoadjuvant and adjuvant phase, 42.3% of keytruda patients and 21.3% of chemotherapy placebo patients had immune-mediated adverse events and infusion reactions "This innovative trial is the first clinical trial in which keytruda combined with new adjuvant and adjuvant therapy is used in patients with early TNBC," said Dr Roger M Perlmutter, President of the MSDR research laboratory The results of the keynote-522 study reported today are very encouraging and may change the clinical treatment of TNBC patients " Keytruda's breast cancer clinical development program includes a number of internal and external collaborative studies, including three ongoing TNBC registration support studies (keynote-355, keynote-242, and keynote-522) Breast cancer is the most common type of cancer among women, with more than 2 million confirmed cases every year around the world TNBC accounts for about 15-20% of all breast cancers Compared with other types of breast cancer, TNBC is more common in women under 50 years old TNBC refers to breast cancer with negative expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) It is an invasive breast cancer with rapid progress, poor prognosis, high recurrence rate and 5-year survival rate of less than 15% TNBC has no effect on hormone therapy and HER2 targeted therapy (such as Herceptin) Metastatic TNBC is one of the most aggressive and refractory breast cancer It is worth mentioning that in March this year, the US FDA accelerated the approval of Roche PD-L1 tumor immunotherapy tecentriq combined with chemotherapy (Abraxane) for the first-line treatment of PD-L1 positive non resectable locally advanced or metastatic TNBC patients This approval makes tecentriq + Abraxane combination the first cancer immunotherapy for PD-L1 positive metastatic TNBC In phase III clinical study impression130, tecentriq + Abraxane significantly reduced the risk of disease progression or death in PD-L1 positive patients by 40% compared with placebo + Abraxane (median PFS: 7.4 months vs 4.8 months, HR = 0.60, 95% CI: 0.48-0.77, P < 0.0001) New data released at the ASCO meeting in 2019 showed that tecentriq + Abraxane regimen improved the overall survival (OS) of patients with PD-L1 positive by 7 months compared with placebo + Abraxane regimen (median OS: 25.0 vs 18.0 months, HR = 0.71, 95% CI: 0.54-0.93) Original source: Merck's keytruda? (pembrolizumab) plus chemotherapy shown statistically significant increase in systemic complete response versa chemotherapy as neoadjuvant therapy in early stage triple negative breast cancer (TNBC)