Categories: world

Frontline Atezolizumab and Nab Paclitaxel Demonstrate PFS Benefit in PD-L1 + mTNBC

30 trial presented at the ESMO Congress 2018. "IMpassion130 is the first phase III trial to show an advantage of…

30 trial presented at the ESMO Congress 2018.

“IMpassion130 is the first phase III trial to show an advantage of first line immunotherapy in triple-negative breast cancer,” said lead study author Peter Schmid, FRCP , MD, PhD, Leader at the Center for Experimental Cancer Medicine, Barts Cancer Institute in London, UK. “Atezolizumab with neighbor paclitaxel resulted in a statistically significant benefit in progression-free survival, both for the purpose of treating the population and the PD-L1 positive population.”

The double blind study evaluated the efficacy and safety of PD-L1 inhibitor plus chemotherapy versus nabacaclitaxel only in treatment-naïve patients with metastatic TNBC. Patients were randomized to 1: 1 to receive nabacaclitaxel at 100 mg / m 2 intravenously on days 1, 8 and 15 in the 28-day cycle of atezolizumab at 840 mg intravenously (n = 451) on day 1 and 15 in a 28-day cycle or with placebo (n = 451). The treatment was given to disease progression or unacceptable toxicity.

The primary priorities were the PFS and overall survival (OS) in both the intentions of treating (ITT) and PD-L1 positive populations; Secondary endpoints were overall response rate, duration of response and security. Patients were stratified by earlier taxan use, liver metastases and PD-L1 expressions, which were defined as at least 1% on tumor-infiltrating immune cells to be positive.

Results of the primary PFS analysis in PD-L1 positive population showed a clinically meaningful median PFS of 7.5 months (95% CI, 6.7-9.2) with atezolizumab / nab paclitaxel and 5, 0 months (95% CI, 3.8-5.6) with chemotherapy (HR, 0.62, 95% CI, 0.49-0.78; P <.0001), showing a 38% reduction in the risk of progression or death. Furthermore, the 1-year PFS rates were 29% (95% CI, 22% -36%) and 16% (95% CI, 11% -22%) and atezolizumab / nabacaclitaxel and nabacaclitaxel respectively. 19659002] In the ITT population, the median PFS with atezolizumab / nab paclitaxel and nabacaclitaxel was 7.2 months (95% CI, 5.6-7.5) and 5.5 months (95% CI, 5,3- 5.6) (HR, 0.80, 95% CI, 0.69-0.92; P = .0025). Furthermore, the 1-year PFS rate was 24% (95% CI, 20% -28%) in the combination arm and 18% (95% CI, 14% -21%) in the nabaclaslitaxel arm.

In a 12.9 month follow-up, a preliminary OS analysis of PD-L1 positive population showed a clinically meaningful improvement with added atezolizumab at 25.0 months compared to nabacaclitaxel only at 15.5 months (HR, 0.62, 95% CI, 0.45-0.86). Two-year operating systems were 54% and 37% in respective immunotherapy / chemotherapy and chemotherapy arms respectively. In the ITT population, P was the value of OS 0.840 (HR, 0.84, 95% CI, 0.69-1.02). However, Schmid stressed that the operating system was not formally tested in a statistical design.

“For me, it is clearly a PD-L1 positive story at the moment. All benefits were in the PD-L1 positive subgroup,” explains Schmid. “Although the ITT group is positive, looking at the subgroups of PD- L1 negative group, there is no benefit. There is no disadvantage, but there is no benefit justifying the use [of the combination] of this [PD-L1–negative] group. “

To be eligible for enrollment, patients must have had metastatic or inoperable locally advanced TNBC without prior treatment for their advanced disease with an ECOG performance status of 0 or 1. Previous chemotherapy in the hardened setting, including taxanes, was allowed if The treatment-free interval was longer than 12 months.

The most serious adverse events (AEs) were similar to the arms. The most common grade 3/4 AE with atezolizumab / nabacaclitaxel and nabacaclitaxel was neutropenia (8% vs. 8%), decreased neutrophil count (5% vs 3%), peripheral neuropathy (6% vs. 3%), fatigue (4% vs. 3%) and anemia (3% vs. 3%).

TNBC stands for 15 % of breast cancer. Those with advanced or metastatic disease usually experience poor results compared to other breast cancer subtypes, with a median OS of 18 months or less, Schmid explains. Standard frontline treatment contains tax or anthrombosis. acyclins, and no targeted therapies have improved the OS so far, he said. The reason for using control-point inhibition depends on how PD-L1 can inhibit the immune system against cancer, and in TNBC, PD-L1 is primarily expressed on tumor-infiltrating lymphocytes.

Nadia Harbeck, MD, Doctor, Head of Breast Center and Oncology Day Clinic, Women’s Hospital at the University of Munich, Germany, shared their perspective on data in a press conference at the meeting.

“We have many patients out there right now on clinical trials with immunotherapy, but so far in breast cancer we have not seen the enormous effects we’ve seen in melanoma or lung cancer,” said Harbeck. “This is the first time we have a phase III study that shows that immunotherapy in triple-negative breast cancer improves survival, and I think this is something that will change how we train in triple-negative breast cancer. “
Addition of atezolizumab (Tecentriq) to nabaclaxel (Abraxane) was found to reduce the risk of progression or death by 38% compared to neighbor paclitaxel only in patients with TNBC with PD-L1 positive metastatic triple-negative breast cancer (TNBC), according to Results from the Phase III IMpassion130 trial presented at the ESMO Congress from 2018.

“IMpassion130 is the first phase III trial to show an advantage of first line immunotherapy in triple negative breast cancer,” said lead study author Peter Schmid , FRCP, MD, PhD, Leader at the Center for Experimental Cancer Medicine, Barts Cancer Institute in London, UK. “Atezolizumab with neighbor paclitaxel resulted in a statistically significant benefit in progression-free survival, both for the purpose of treating the population and the PD-L1 positive population.”

The double blind study evaluated the efficacy and safety of PD-L1 inhibitor plus chemotherapy versus nabacaclitaxel only in treatment-naïve patients with metastatic TNBC. Patients were randomized to 1: 1 to receive nabacaclitaxel at 100 mg / m 2 intravenously on days 1, 8 and 15 in the 28-day cycle of atezolizumab at 840 mg intravenously (n = 451) on day 1 and 15 in a 28-day cycle or with placebo (n = 451). The treatment was given to disease progression or unacceptable toxicity.

The primary priorities were progression-free survival (PFS) and overall survival (OS) in both intentions (ITT) and PD-L1 positive populations; Secondary endpoints were overall response rate, duration of response and security. Patients were stratified by earlier taxan use, liver metastases and PD-L1 expressions, which were defined as at least 1% on tumor-infiltrating immune cells to be positive.

Results of the primary PFS analysis in PD-L1 positive population showed a clinically meaningful median PFS of 7.5 months (95% CI, 6.7-9.2) with atezolizumab / nab paclitaxel and 5, 0 months (95% CI, 3.8-5.6) with chemotherapy (HR, 0.62, 95% CI, 0.49-0.78; P <.0001). Furthermore, the 1-year PFS rates were 29% (95% CI, 22% -36%) and 16% (95% CI, 11% -22%) and atezolizumab / nabacaclitaxel and nabacaclitaxel respectively. 19659002] In the ITT population, the median PFS with atezolizumab / nab paclitaxel and nabacaclitaxel was 7.2 months (95% CI, 5.6-7.5) and 5.5 months (95% CI, 5,3- 5.6) (HR, 0.80, 95% CI, 0.69-0.92; P = .0025). Furthermore, the 1-year PFS rate was 24% (95% CI, 20% -28%) in the combination arm and 18% (95% CI, 14% -21%) in the nabaclaslitaxel arm.

In a 12.9 month follow-up, a preliminary OS analysis of PD-L1 positive population showed a clinically meaningful improvement with added atezolizumab at 25.0 months compared to nabacaclitaxel only at 15.5 months (HR, 0.62, 95% CI, 0.45-0.86). Two-year operating systems were 54% and 37% in respective immunotherapy / chemotherapy and chemotherapy arms respectively. In the ITT population, P was the value of OS 0.840 (HR, 0.84, 95% CI, 0.69-1.02). However, Schmid stressed that the operating system was not formally tested in a statistical design.

“For me, it is clearly a PD-L1 positive story at the moment. All benefits were in the PD-L1 positive subgroup,” explains Schmid. “Although the ITT group is positive, looking at the subgroups of PD- L1 negative group, there is no benefit. There is no disadvantage, but there is no benefit justifying the use [of the combination] of this [PD-L1–negative] group. “

To be eligible for enrollment, patients must have had metastatic or inoperable locally advanced TNBC without prior treatment for their advanced disease with an ECOG performance status of 0 or 1. Previous chemotherapy in the hardened setting, including taxanes, was allowed if The treatment-free interval was longer than 12 months.

The most serious adverse events (AEs) were similar to the arms. The most common grade 3/4 AE with atezolizumab / nabacaclitaxel and nabacaclitaxel was neutropenia (8% vs. 8%), decreased neutrophil count (5% vs 3%), peripheral neuropathy (6% vs. 3%), fatigue (4% vs. 3%) and anemia (3% vs. 3%).

TNBC stands for 15 % of breast cancer. Those with advanced or metastatic disease usually experience poor results compared to other breast cancer subtypes, with a median OS of 18 months or less, Schmid explains. Standard frontline treatment contains tax or anthrombosis. acyclins, and no targeted therapies have improved the OS so far, he said. The reason for using control-point inhibition depends on how PD-L1 can inhibit the immune system against cancer, and in TNBC, PD-L1 is primarily expressed on tumor-infiltrating lymphocytes.

Nadia Harbeck, MD, Doctor, Head of Breast Center and Oncology Day Clinic, Women’s Hospital at the University of Munich, Germany, shared their perspective on data in a press conference at the meeting.

“We have many patients out there right now on clinical trials with immunotherapy, but so far in breast cancer we have not seen the enormous effects we’ve seen in melanoma or lung cancer,” said Harbeck. “This is the first time we have a phase III study that shows that immunotherapy in triple-negative breast cancer improves survival, and I think this is something that will change how we train in triple-negative breast cancer. “


Reference :
Schmid P. IMpassion130: Results from a global randomized, double-blind, phase 3 study of atezolizumab (atezo) + nab-paclitaxel (nab-P) versus placebo + nab-P in treatment-naïve, locally advanced or metastatic triple-negative breast cancer mTNBC). I: Progress of the ESMO Congress from 2018; 19-23 October, 2018; Munich, Germany. Summary LBA1_PR.

Share
Published by
Faela