Adding Immunotherapy to Chemotherapy Extends Survival in Metastatic Triple-Negative Breast Cancer

TOP - February 2019, Vol 12, No 1 - Breast Cancer, Immunotherapy
Phoebe Starr

Munich, Germany—Triple-negative breast cancer is considered one of the most difficult to treat breast cancers, with few treatment options, but finally a breakthrough study shows progress by extending patient survival. Results of the phase 3 ­IMpassion130 clinical trial show that using the checkpoint inhibitor atezolizumab (Tecentriq), a PD-L1 inhibitor, with nab-paclitaxel (Abrax­ane) chemotherapy significantly extended survival in patients with advanced or metastatic triple-negative breast cancer.

Lead investigator, Peter Schmid, MD, PhD, FRCP, Centre Lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, United Kingdom, presented the study results at the ESMO 2018 Congress.

Exciting Results

The addition of immunotherapy to chemotherapy improved median progression-free survival (PFS) from 5.5 months with nab-paclitaxel plus placebo to 7.2 months (hazard ratio [HR] to progression/death, 0.80; 95% confidence interval [CI], 0.69-0.92; P = .002); the results were even better in the subgroup of patients with PD-L1–positive disease, with a median PFS of 7.5 months with the combination versus 5 months with chemotherapy alone (HR, 0.62; 95% CI, 0.49-0.78; P <.001).

Patients are continuing to benefit from this combination therapy and are still being followed, and the survival data have not yet matured. However, an interim analysis of survival showed that atezolizumab plus nab-paclitaxel significantly improved the median overall survival (OS), with 21.3 months OS in the immunotherapy plus chemotherapy group versus 17.6 months in the chemotherapy alone group. In patients with PD-L1–positive triple-negative breast cancer, the median OS was 25 months versus 15.5 months, respectively—a 10.5-month advantage.

The study results were published in the New England Journal of Medicine1 to coincide with the ESMO meeting.

“These results will change the way triple-negative breast cancer is treated. Atezolizumab in combination with nab-paclitaxel is the first targeted treatment to improve survival in metastatic triple-negative breast cancer. It is also the first immune therapy to improve outcomes in this cancer,” stated Dr Schmid.

“This combination should become a new treatment option for patients with metastatic triple-negative breast cancer,” Dr Schmid advised.

Dr Schmid noted that focusing on the median PFS in immunotherapy studies can be misleading, because checkpoint inhibitor treatment can lead to durable responses that are not apparent in PFS curves.

“The reduction in progression-free survival or death by 20% in the overall population and by almost 40% in the PD-L1–positive population is a better way to look at the impact of immunotherapy on PFS,” he stated.

IMpassion130 Trial

IMpassion130 enrolled 902 patients at 246 sites in 41 countries with previously untreated metastatic triple-negative breast cancer. All patients provided tissue specimens for assessment of PD-L1 status. The patients were randomized to atezoliz­umab plus nab-paclitaxel or to placebo plus nab-paclitaxel, and received treatment until disease progression or unacceptable toxicity. The median follow-up was 12.9 months.

The overall response rate was 56% in the atezolizumab plus chemotherapy arm versus 45.9% in the nab-pac­litaxel alone arm. In patients with PD-L1–positive disease, the response rates were 58.9% and 42.6%, respectively. The median duration of response in the intent-to-treat analysis was 7.4 months with the immunotherapy combination and 5.6 months with chemotherapy alone. In patients with PD-L1–positive triple-negative breast cancer, the median duration of response was 8.5 months and 5.5 months, respectively.

No new adverse events were reported in the study. The percentage of adverse events was similar in both arms, as was the type and severity of adverse events, which may suggest an increasing role of chemotherapy in the overall percentage of side effects. The most common immune-­related adverse event was hypothyroidism in patients who received atezolizumab (17.3%) compared with 4.3% in the placebo arm. Adverse events leading to treatment dis­continuation were reported in 15.9% of patients receiving the combination versus 8.2% of those receiving chemotherapy alone.

ESMO Expert Marleen Kok, MD, PhD, Medical Oncologist, The Netherlands Cancer Institute, Amsterdam, said, “This is the first randomized phase 3 trial providing evidence that adding immunotherapy to standard chemotherapy increases progression-free survival in metastatic triple-negative breast cancer, particularly in patients with PD-L1–positive tumors, and extends survival in the PD-L1–positive subgroup.”

“While the benefit in terms of progression-free survival was relatively small, around 3 months, the gain in overall survival in the PD-L1–positive patients was impressive with a 10-month benefit. The IMpassion130 data will probably change the treatment landscape for our metastatic triple-negative breast cancer patients,” Dr Kok added. l


  1. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nabpaclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018 Oct 20. Epub ahead of print.
Related Items
Pembrolizumab Added to First-Line Chemotherapy Improves Progression-Free Survival in Metastatic TNBC
William King
TOP - September 2020 Vol 13, No 5 published on September 14, 2020 in Breast Cancer
Atezolizumab, Vemurafenib, and Cobimetinib Triplet Therapy Improves PFS in BRAF-Positive Melanoma
Phoebe Starr
Web Exclusives published on August 17, 2020 in AACR Highlights
SBRT plus Immunotherapy in Metastatic Renal-Cell Carcinoma Warrants Further Study
TOP - July 2020, Vol 13, No 4 published on July 15, 2020 in Immunotherapy
Capecitabine Improves Outcomes in TNBC When Added to Other Systemic Therapy
TOP - July 2020, Vol 13, No 4 published on July 15, 2020 in Breast Cancer
Promising 3-Drug Regimen for Advanced Gastric Cancer, Regardless of PD-L1 Expression
Wayne Kuznar
TOP - May 2020, Vol 13, No 3 published on May 21, 2020 in Immunotherapy
Sitravatinib, Novel TKI, plus Nivolumab Elicits Good Responses in Renal-Cell Carcinoma
Phoebe Starr
TOP - May 2020, Vol 13, No 3 published on May 21, 2020 in Emerging Therapies
First-in-Class Oral MK-6482 Shows Exciting Results in Clear-Cell Renal-Cell Carcinoma
Phoebe Starr
TOP - May 2020, Vol 13, No 3 published on May 21, 2020 in Emerging Therapies, Renal-Cell Carcinoma
Real-World Healthcare Utilization and Costs Support Broader Use of CAR T-Cell Therapy
Phoebe Starr
TOP - March 2020, Vol 13, No 2 published on March 11, 2020 in Value-Based Care
Mosunetuzumab, a Dual-Targeted Antibody, Shows Complete Remissions in Relapsed/Refractory NHL After CAR T-Cell Therapy By
Phoebe Starr
TOP - March 2020, Vol 13, No 2 published on March 11, 2020 in ASH 2019 Highlights
Improving Access to Genetic Cancer Screening in a Medically Underserved Community
Phoebe Starr
TOP - March 2020, Vol 13, No 2 published on March 11, 2020 in ACCC
Last modified: April 27, 2020