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

Reference

  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
Avelumab plus Axitinib Combination Improves Outcomes in Advanced Renal-Cell Carcinoma
Wayne Kuznar
TOP - February 2019, Vol 12, No 1 published on January 29, 2019 in Immunotherapy, Renal-Cell Carcinoma
Alpelisib First Drug to Improve Outcomes in Advanced Breast Cancer with PIK3CA Mutation
TOP - February 2019, Vol 12, No 1 published on January 29, 2019 in Breast Cancer
Nivolumab–Ipilimumab Combination Highly Active in Metastatic MSI-H or dMMR Colorectal Cancer
TOP - February 2019, Vol 12, No 1 published on January 29, 2019 in Immunotherapy
Omega-3 Fatty Acids Significantly Reduced Pain in Obese Patients with Breast Cancer
Meg Barbor, MPH
TON - November 2018, Vol 11, No 5 published on November 28, 2018 in Breast Cancer
Building on the Successes of Cancer Immunotherapy
Charles Bankhead
TON - November 2018, Vol 11, No 5 published on November 28, 2018 in Immunotherapy
Investigational CAR T-Cell Therapy, bb2121, Shows Durable Responses in Relapsed or Refractory Multiple Myeloma
Wayne Kuznar
TON - November 2018, Vol 11, No 5 published on November 28, 2018 in Immunotherapy
Nivolumab plus Ipilimumab Combo Controls Brain Metastases in Patients with Melanoma
Phoebe Starr
TON - November 2018, Vol 11, No 5 published on November 28, 2018 in Melanoma
TLR9 Agonist plus Immunotherapy May Overcome Resistance to PD-1 Inhibition
Phoebe Starr
TON - November 2018, Vol 11, No 5 published on November 28, 2018 in Emerging Therapies
With Access to Care, Black Men in the United States Have Same Prostate Cancer Outcomes as White Men
Phoebe Starr
TON - September 2018, Vol 11, No 4 published on September 19, 2018 in Prostate Cancer
A Home Run for Pembrolizumab plus Chemotherapy Combination in Newly Diagnosed Metastatic Non–Small-Cell Lung Cancer
Phoebe Starr
TOP - August 2018, Vol 11, No 2 published on August 3, 2018 in Lung Cancer
Last modified: January 29, 2019