Adding Tecentriq (atezolizumab) to chemotherapy did not improve survival compared to chemotherapy alone in patients with triple-negative breast cancer (TNBC) whose disease relapsed within a year of their last treatment for early breast cancer, according to findings from the phase 3 IMpassion132 clinical trial.
Findings from the study were presented at the 2024 ESMO Breast Cancer Congress.
Study Highlights:
- The addition of Tecentriq did not improve survival compared to chemotherapy alone in patients with triple-negative breast cancer.
- The median overall survival was 11.2 months with chemotherapy alone and 12.1 months with Tecentriq plus chemotherapy, so the researchers could not say for certain that one treatment was better than the other.
- More research is needed to develop new therapies for this group of patients.
- Doctors need to consider the different types of TNBC when making treatment decisions.
At a median follow-up of 9.8 months, the median overall survival (OS; time patients live before death of any cause) was 11.2 months with chemotherapy alone (177 patients) compared to 12.1 months with Tecentriq plus chemotherapy (177 patients) in patients with PD-L1–positive TNBC. Of note, PD-L1 is the protein that Tecentriq targets to help activate the immune system against the cancer.
The difference between these two OS outcomes was not statistically significant, meaning that the researchers could not say with certainty that one regimen was better than the other.
Although not formally, these results were consistent in the modified study population, with a median OS of 9.8 months with chemotherapy alone (192 patients) compared to 10.4 months with Tecentriq plus chemotherapy (188 patients). Again, the difference between the two OS outcomes was not statistically significant.
“Novel therapies and trial designs are urgently required for this treatment-resistant population and these data highlight the importance of recognizing, as we have before, that TNBC is highly heterogeneous — especially in the first-line setting,” Dr. Rebecca A. Dent, of the National Cancer Center Singapore and Duke-NUS Medical School, in Singapore, said in a presentation of the data. “We now recognize that PD-L1–positive and negative patients have a very different prognosis. We’ve also realized that patients who harbor PIK3CA mutations also have a different prognosis, and we know that patients who have de novo metastatic TNBC [meaning the disease has already spread at the time of diagnosis] also clearly have a different prognosis than those who have received neoadjuvant therapy and were exposed to a number of agents by the time they reach their first-line status. As we are here discussing novel trial designs for early-relapsing TNBC, I really think we need to take this into account.”
About half of patients who develop metastatic TNBC after standard presurgical or postsurgical chemotherapy will relapse within one year of chemotherapy completion. Early relapsing TNBC represents a biologically and clinically distinct entity in that it is typically resistant to standard options and is more prevalent in younger patients who have large primary tumors that do not harbor BRCA alterations, Dent explained.
Notably, the majority of clinical trials do not include those patients, which “poses a real challenge for us in clinical practice,” she underscored.
About the IMpassion132 Trial
The phase 3 IMpassion132 trial enrolled patients with unresectable locally advanced or metastatic TNBC who previously received an anthracycline and taxane for early disease and experienced progressive disease within one year after their last curative-intent treatment. They could not have previously received chemotherapy for advanced disease, and their PD-L1 status needed to be available.
Participants were randomly assigned to investigator-selected chemotherapy in the form of gemcitabine plus carboplatin or capecitabine with or without Tecentriq. Treatment continued until progressive disease or intolerable side effects.
OS served as the trial’s main goal. Patients who were PD-L1 positive were evaluated, and if positive, modified.
“In August of 2019, we saw the results of the IMpassion130 study, which clearly showed us that the benefits of immune checkpoint inhibition were largely driven by those patients who had PD-L1–positive metastatic TNBC, which is similar to what we’ve observed in the KEYNOTE-355 study using [Keytruda (pembrolizumab)],” Dent said.
The primary analysis was planned when a prespecified number of 247 deaths occurred in the PD-L1–positive subgroup. If positive, investigators would then look at the modified population, which included patients irrespective of PD-L1 status.
The median patient age was 48 years in the chemotherapy-alone and Tecentriq groups, respectively. Slightly more than half of patients had an ECOG performance status of 0 (57% versus 62%), indicating that they could perform all their daily tasks with no difficulty or assistance. Eighteen percent in both arms had prior exposure to platinum-based chemotherapy; 27% and 29% of patients, respectively previously received capecitabine. More than half of patients were without complications or recurrence of their disease for less than six months (69% versus 66%) and had lung and/or liver metastases (62% versus 60%). Investigator-selected chemotherapy was carboplatin/gemcitabine for 73% and capecitabine for 27% of those in both arms.
“What you can see is in those patients, and remember, this is about three-quarters of the patients who had a [disease-free interval] of less than six months, the median OS was only 9.4 months in the control arm and 11.3 months in the [Tecentriq] arm. But you can see in both of these subgroups, whether they relapsed less than six months or greater than six months, there was no statistically significant improvement in OS with the addition of Tecentriq.”
The median progression-free survival (PFS; time after treatment patients live without their disease worsening) in the chemotherapy-only arm was 3.6 months versus 4.2 months in the Tecentriq arm.
The unconfirmed objective response rates (percentage of patients whose disease shrunk or disappeared) in the respective arms were 28% and 40% respectively, translating to a percentage difference of 11%.
The median duration of response in the placebo arm was 4.1 months versus 6.6 months in the Tecentriq arm. Data for these secondary end points in the modified population proved to be consistent, according to Dent.
Safety was evaluated in a total of 587 patients (294 in the chemotherapy-only group and 293 in the Tecentriq group). A side effect of any severity occurred in 96% of those in the placebo arm and 96% in the Tecentriq arm; these effects were treatment related for 91% and 90% of patients, respectively. Treatment-related grade 3 or 4 side effects (meaning that they were moderate to severe) occurred in 71% and 67% of patients, respectively, and were grade 3 or 4 for 65% and 62% of patients, respectively.
Two patients in the chemotherapy-only arm experienced a treatment-related death, while four patients in the Tecentriq arm died, only one of which was determined to be treatment related. Side effects of special interest occurred in 54% and 61% of patients, respectively. Side effects led to treatment discontinuation for 11% of those in the placebo arm and 15% of those in the Tecentriq arm.
“No new safety signals were observed,” Dent concluded.
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