This article is more than 5 years old. Information may no longer be current.
Atezolizumab combination extends survival for some patients with metastatic triple-negative breast cancer
Click Here to Manage Email Alerts
MUNICH — The addition of atezolizumab to nab-paclitaxel conferred a modest but statistically significant PFS benefit among patients with metastatic triple-negative breast cancer, according to study results presented at European Society for Medical Oncology Congress.
The regimen also conferred a clinically meaningful OS benefit among patients with PD-L1 positive disease.
“Patients with triple-negative breast cancer have inferior survival outcomes compared with those who have other breast cancer subtypes. Median OS ranges between 15 and 18 months, and there is no established targeted therapy to improve outcomes for this patient population,” Peter Schmid, MD, PhD, FRCP, clinical director of St. Bartholomew Breast Cancer Centre in London and lead of the Centre of Experimental Cancer Medicine at Barts Cancer Institute, said during a press briefing. “However, immune checkpoint inhibitors appear promising in triple-negative disease. PD-L1 expression can inhibit immune response in certain cancers, and most of the PD-L1 expression in triple-negative breast cancer is in immune cells.”
The phase 3 IMPassion130 trial included 902 patients with previously untreated metastatic triple-negative disease.
All patients received 100 mg/m² IV nab-paclitaxel alone on days 1, 8 and 15 of 28-day cycles. Researchers randomly assigned half of the patients to also receive 840 mg IV atezolizumab (Tecentriq, Genentech) — an anti-PD-L1 monoclonal antibody — on days 1 and 15 of each cycle.
Treatment continued until disease progression.
Investigators stratified patients based upon taxane use, liver metastases and tumor PD-L1 expression on immune cells, with positivity defined as expression of 1% or greater. Treatment groups were balanced with regard to age, ECOG performance status and prior neoadjuvant treatment.
PFS and OS in the intention-to-treat population and PD-L1-positive subgroup served as coprimary endpoints. Safety, objective response and duration of response served as secondary endpoints.
Median follow-up was 12.9 months.
Results showed atezolizumab plus nab-paclitaxel improved median PFS among the intention-to-treat population (7.2 months vs. 5.5 months; HR = 0.8; 95% Ci, 0.69-0.92) and the PD-L1-positive subgroup (7.5 months vs. 5 months; HR = 0.62; 95% Ci, 0.49-0.78).
More than half of patients remained alive at data cutoff.
An interim OS analysis showed median survival of 21.3 months with the atezolizumab regimen and 17.6 months with nab-paclitaxel alone. This difference did not reach statistical significance.
However, the atezolizumab regimen conferred a considerable OS benefit to patients with PD-L1-positive disease (median, 25 months vs. 15.5 months; HR = 0.62; 95% CI, 0.45-0.86).
“If it was just a PFS story, we would say this is a modest benefit,” Schmid said. “To me, though, the important message is we see the same hazard ratio for overall survival, with a nearly 10-month difference in the PD-L1-positive group — and this is a disease for which we have not managed to improve survival with any targeted therapy. I personally feel this will be clinically meaningful.”
Researchers reported significantly higher ORRs with atezolizumab in the intention-to-treat population (56% vs. 46%; P = .0021) and the PD-L1-postiive subgroup (59% vs. 43%; P = .0016).
Nearly all patients in both treatment groups experienced at least one adverse event. Rates of grade 3 or grade 4 adverse events were slightly higher among patients assigned atezolizumab (49% vs. 42%). Adverse events that occurred with at least 5% greater frequency in the atezolizumab group included nausea, cough, neutropenia, pyrexia and hypothyroidism.
“The combination therapy was well tolerated, with a safety profile consistent with each agent alone,” Schmid said. “This combination should become a new treatment option for patients with metastatic triple-negative breast cancer.” – by Jennifer Southall
Reference: Schmid P, et al. Abstract LBA1_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.
Disclosure s : Schmid repots honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Novartis, Pfizer, Puma and Roche/Genentech, as well as grants or support/contracted research to his institution from Astellas, AstraZeneca, Medivation, Novartis, OncoGenex and Roche/Genentech. Schmid’s wife is an employee of Roche. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
Back to Top
Elias Obeid, MD, MPH
IMpassion130 is the first randomized phase 3 clinical trial to investigate immune checkpoint blockade along with chemotherapy in metastatic triple-negative breast cancer.
The trial met its primary endpoint of showing a prolonged PFS when atezolizumab, a PD-L1 inhibitor, was added to nab-paclitaxel as a first-line treatment in the metastatic setting. This benefit was observed in the intention-to-treat analysis, and was slightly more pronounced among those patients whose tumors expressed PD-L1 on the infiltrating immune cells in the tumor.
The study only included patients who did not receive any prior treatment for their metastatic triple-negative breast cancer. We do not yet know the effect of adding immune checkpoint blockade to subsequent lines of treatment beyond the first line. We also do not know how this effect would be with different classes of chemotherapy.
Although OS was not prolonged for the intention-to-treat analysis, an analysis of the PD-L1 subgroup showed a significant improvement in median OS favoring atezolizumab (25 months vs. 15.5 months). This is particularly interesting, raising questions about whether immune checkpoint blockade improves the benefit of subsequent lines of chemotherapy.
Although there were no new side effects beyond what’s known for chemotherapy alone or immunotherapy alone, in this study there were significantly more adverse events when atezolizumab was added to chemotherapy.
Finally, in this trial, PD-L1 was used as a biomarker to stratify benefit in a preplanned analysis. We do not know what other biomarkers would be of importance in triple-negative breast cancer and immune checkpoint blockade.
Perspective
Back to Top
Massimo Cristofanilli, MD
This is another example of precision medicine, as it highlights that you cannot treat every patient the same way. You must be very selective based on factors such as PD-L1 expression. Second, this will greatly impact the design of other studies. Giving chemotherapy alone probably would not be allowed anymore. I think it would be unethical. Also, giving immunotherapy to patients who are PD-L1 negative would be very difficult to justify as an inclusion criterion. So it will have major impact on the way other studies are designed, and this will help us get a much faster understanding of how immunotherapy will impact triple-negative breast cancer.
Perspective
Back to TopNadia Harbeck, MD, PhD
Prognosis is dismal for triple-negative breast cancer once it becomes metastatic. We have a lot of patients on clinical trials with immunotherapy but, so far in breast cancer, we have not seen the impressive effects that we have seen in melanoma or lung cancer. This is the first time we have a phase 3 trial proving immunotherapy in triple-negative breast cancer improves survival. This is something that will change our practice for triple-negative disease.
Had we known the results that we saw presented here, the trial probably would have been designed differently to just look at the targeted population.
However, in the other cancers for which immune therapy has played such a big role, we have seen the impact on OS is sometimes larger than on PFS. That has to do with the unique mechanism of action of immunotherapy versus just chemotherapy. The data in this study are quite consistent with that observation. Also, it is important to note the OS data are preliminary. We are expecting to see more solid data in the future.
Read more about
Click Here to Manage Email Alerts