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Peter Schmid, FRCP, MD, PhD
The combination atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) showed a benefit of 2.5 months in terms of progression-free survival (PFS) compared with nab-paclitaxel alone in patients with a Metastatic metastatic triple negative breast cancer (TNBC) positive for PD-L1. , according to the findings of the IMpassion130 Phase III trial presented at ESMO 2018.
"IMpassion130 is the first phase III trial to demonstrate the benefits of first-line immunotherapy against triple negative breast cancer," said lead author of the study, Peter Schmid, FRCP , MD, PhD, head of the Center for Experimental Cancer Medicine, Barts Cancer Institute. in London, United Kingdom. "The atezolizumab associated with nab-paclitaxel resulted in a statistically significant benefit for progression-free survival, both in the intention-to-treat population and in the PD-L1 positive population."
The double-blind study evaluated the efficacy and safety of the PD-L1 inhibitor-associated chemotherapy compared to nab-paclitaxel alone in treatment-naive patients with TNBC metastatic. Patients were randomized 1: 1 to receive nab-paclitaxel 100 mg / m2 intravenously on days 1, 8 and 15 of the 28-day cycle with atezolizumab at 840 mg intravenously (n = 451) on days 1 and 15 of a 28-day cycle or with placebo (n = 451) ). The treatment was administered until disease progression or unacceptable toxicity.
The primary endpoints were PFS and overall survival (OS) in both intent-to-treat (ITT) and PD-L1-positive patients; the secondary evaluation criteria were the overall response rate, the duration of the response and the security. Patients were stratified based on past use of taxanes, hepatic metastases, and PD-L1 expression, defined as being positive for at least 1% of the infiltrating immune cells in the tumor.
The results of the primary analysis of SSP in the population positive for PD-L1 showed a clinically significant median PFS of 7.5 months (95% CI, 6.7-9.2) with atezolizumab / nab-paclitaxel and at 5.0 months (95% CI, 3.8-5.6) with chemotherapy (HR, 0.62, 95% CI, 0.49-0.78; P <0.0001), demonstrating a 38% reduction in the risk of progression or death. In addition, one-year PHI rates were 29% (95% CI, 22% to 36%) and 16% (95% CI, 11% to 22%) with atezolizumab / nab-paclitaxel and nab-paclitaxel.
In the ITT population, the median PFS with atezolizumab / nab-paclitaxel and nab-paclitaxel was 7.2 months (95% CI, 5.6-7.5) and 5.5 months (95% CI, 5%). , 3-5.6), respectively (HR 0.80; 95;% CI, 0.69-0.92; P = 0.0025). In addition, one-year PHI rates were 24% (95% CI, 20% to 28%) in the combination group and 18% (95% CI, 14% to 21%) in the nab group. -paclitaxel.
At a follow-up of 12.9 months, an interim analysis of positive population density for PD-L1 showed clinically significant improvement with atezolizumab added at 25.0 months compared to nab-paclitaxel alone at 15 , 5 months (HR, 0.62, 95% CI, 0.45 -0.86). Two-year ILI rates were 54% and 37%, respectively, in the immunotherapy / chemotherapy and chemotherapy groups. In the ITT population, the P the OS value was 0.0840 (HR, 0.84, 95% CI, 0.69-1.02). However, Schmid pointed out that the OS was not formally tested in a statistical design.
"For me, for now, it's clearly a positive story for PD-L1 – all the benefits were in the positive subgroup for PD-L1," Schmid explained. "Although the ITT group is positive, if you look at the subgroups of the PD-L1 – negative group, you do not get any benefit. There is no harm, but no benefit warrants the use [of the combination] in this [PD-L1–negative] group."
To be eligible, patients must have been treated with metastatic or locally advanced TNBC, without prior treatment for their advanced disease, with an ECOG performance status equal to 0 or 1. Previous chemotherapy in the curative setting, including taxanes, was allowed if the free interval was longer than 12 months.
In terms of safety, most adverse events (AEs) across all grades were similar between arms. The most common adverse effects with grade 3/4 atezolizumab / nab-paclitaxel and nab-paclitaxel were neutropenia (8% vs. 8%), decreased neutrophil count (5% vs. 3%), peripheral neuropathy ( 6% vs. 3%), fatigue (4% vs. 3%) and anemia (3% vs. 3%), respectively.
TNBC accounts for 15% of breast cancers. Women with advanced or metastatic disease usually have poor results compared to other subtypes of breast cancer, with a median bone of 18 months or less, explained Schmid. Standard front-line therapy includes taxane or anthracyclines, and no targeted treatment has improved OS so far, he said. The rationale for the use of control point inhibition is due to the way in which PD-L1 can inhibit anti-cancer immune responses and, in TNBC, PD-L1 is mainly expressed on infiltrating lymphocytes the tumor.
Nadia Harbeck, MD, PhD, head of the Breast Cancer and Breast Cancer Day Clinic, Women's Hospital of the University of Munich, Germany, presented her perspective on data during A point of the press during the meeting.
"We have a lot of patients currently on clinical trials of immunotherapy, but until now in breast cancer we have not seen the huge effects we've seen on melanoma or the lung cancer, "said Harbeck. "This is the first time we have conducted a phase III trial showing that triple-negative breast cancer immunotherapy improves survival, and I think it will change the way we practice triple negative breast cancer."
The addition of atezolizumab (Tecentriq) to nab-paclitaxel (Abraxane) has been shown to reduce the risk of progression or death by 38% compared with nab-paclitaxel alone in cancer patients. positive metastatic triple-negative metastatic breast (TNBC). , according to the findings of the IMpassion130 Phase III trial presented at ESMO 2018.
"IMpassion130 is the first phase III trial to demonstrate the benefits of first-line immunotherapy against triple negative breast cancer," said lead author of the study, Peter Schmid, FRCP , MD, PhD, head of the Center for Experimental Cancer Medicine, Barts Cancer Institute. in London, United Kingdom. "The atezolizumab associated with nab-paclitaxel resulted in a statistically significant benefit for progression-free survival, both in the intention-to-treat population and in the PD-L1 positive population."
The double-blind study evaluated the efficacy and safety of the PD-L1 inhibitor-associated chemotherapy compared to nab-paclitaxel alone in treatment-naive patients with TNBC metastatic. Patients were randomized 1: 1 to receive nab-paclitaxel 100 mg / m2 intravenously on days 1, 8 and 15 of the 28-day cycle with atezolizumab at 840 mg intravenously (n = 451) on days 1 and 15 of a 28-day cycle or with placebo (n = 451) ). The treatment was administered until disease progression or unacceptable toxicity.
The co-primary endpoints were progression-free survival (PFS) and overall survival (OS) in both intention-to-treat (ITT) and PD-L1 positive populations; the secondary evaluation criteria were the overall response rate, the duration of the response and the security. Patients were stratified based on past use of taxanes, hepatic metastases, and PD-L1 expression, defined as being positive for at least 1% of the infiltrating immune cells in the tumor.
The results of the primary analysis of SSP in the population positive for PD-L1 showed a clinically significant median PFS of 7.5 months (95% CI, 6.7-9.2) with atezolizumab / nab-paclitaxel and at 5.0 months (95% CI, 3.8-5.6) with chemotherapy (HR, 0.62, 95% CI, 0.49-0.78; P <.0001). In addition, one-year PHI rates were 29% (95% CI, 22% to 36%) and 16% (95% CI, 11% to 22%) with atezolizumab / nab-paclitaxel and nab-paclitaxel.
In the ITT population, the median PFS with atezolizumab / nab-paclitaxel and nab-paclitaxel was 7.2 months (95% CI, 5.6-7.5) and 5.5 months (95% CI, 5%). , 3-5.6), respectively (HR 0.80; 95;% CI, 0.69-0.92; P = 0.0025). In addition, one-year PHI rates were 24% (95% CI, 20% to 28%) in the combination group and 18% (95% CI, 14% to 21%) in the nab group. -paclitaxel.
At a follow-up of 12.9 months, an interim analysis of positive population density for PD-L1 showed clinically significant improvement with atezolizumab added at 25.0 months compared to nab-paclitaxel alone at 15 , 5 months (HR, 0.62, 95% CI, 0.45 -0.86). Two-year ILI rates were 54% and 37%, respectively, in the immunotherapy / chemotherapy and chemotherapy groups. In the ITT population, the P the OS value was 0.0840 (HR, 0.84, 95% CI, 0.69-1.02). However, Schmid pointed out that the OS was not formally tested in a statistical design.
"For me, for now, it's clearly a positive story for PD-L1 – all the benefits were in the positive subgroup for PD-L1," Schmid explained. "Although the ITT group is positive, if you look at the subgroups of the PD-L1 – negative group, you do not get any benefit. There is no harm, but no benefit warrants the use [of the combination] in this [PD-L1–negative] group."
To be eligible, patients must have been treated with metastatic or locally advanced TNBC, without prior treatment for their advanced disease, with an ECOG performance status equal to 0 or 1. Previous chemotherapy in the curative setting, including taxanes, was allowed if treatment was allowed. the free interval was longer than 12 months.
In terms of safety, most adverse events (AEs) across all grades were similar between arms. The most common adverse effects with grade 3/4 atezolizumab / nab-paclitaxel and nab-paclitaxel were neutropenia (8% vs. 8%), decreased neutrophil count (5% vs. 3%), peripheral neuropathy ( 6% vs. 3%), fatigue (4% vs. 3%) and anemia (3% vs. 3%), respectively.
TNBC accounts for 15% of breast cancers. Women with advanced or metastatic disease usually have poor results compared to other subtypes of breast cancer, with a median bone of 18 months or less, explained Schmid. Standard front-line therapy includes taxane or anthracyclines, and no targeted treatment has improved OS so far, he said. The rationale for the use of control point inhibition is due to the way in which PD-L1 can inhibit anti-cancer immune responses and, in TNBC, PD-L1 is mainly expressed on infiltrating lymphocytes the tumor.
Nadia Harbeck, MD, PhD, head of the Breast Cancer and Breast Cancer Day Clinic, Women's Hospital of the University of Munich, Germany, presented her perspective on data during A point of the press during the meeting.
"We have a lot of patients currently on clinical trials of immunotherapy, but until now in breast cancer we have not seen the huge effects we've seen on melanoma or the lung cancer, "said Harbeck. "This is the first time we have conducted a phase III trial showing that triple-negative breast cancer immunotherapy improves survival, and I think it will change the way we practice triple negative breast cancer."
Reference:
Schmid P. IMpassion130: Results of a global, randomized, double-blind phase 3 study on atezolizumab (atezo) + nab-paclitaxel (nab-P) vs placebo + nab-P in triple-naive treatment, locally advanced or metastatic negative breast cancer (mTNBC). In: Proceedings of the ESMO 2018 congress; October 19-23, 2018; Munich, Germany. Summary LBA1_PR.
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