Pembrolizumab Continues to Show Durable Activity in Triple-Negative Breast Cancer

TON Web Exclusives - Breast Cancer

Pembrolizumab monotherapy showed manageable toxicity and durable responses in patients with heavily pretreated, metastatic triple-negative breast cancer (mTNBC), regardless of PD-L1 expression. Data from cohort A of the KEYNOTE-086 trial showed an overall response rate (ORR) of 4.7% with single-agent pembrolizumab in this setting,1 announced Sylvia Adams, MD, Associate Professor, Department of Medicine, NYU Langone Health, at the 2017 meeting of the American Society of Clinical Oncology (ASCO).

“The activity of pembrolizumab appeared independent of tumor PD-L1 expression,” Dr Adams said. “Survival was promising in patients who had responded to therapy. Although it requires further investigation, the activity was greater in patients with less heavily pretreated disease.”

TNBC is an aggressive, heterogeneous subtype of breast cancer. The standard of care for women with TNBC is cytotoxic chemotherapy, but median overall survival (OS) resulting from this approach is only 9 to 12 months, and treatment is associated with significant toxicity.2,3

Pembrolizumab has already shown antitumor activity in women with PD-L1–positive mTNBC in the phase 1 KEYNOTE-012 trial.4 This study gave rise to the international, multicohort, phase 2 KEYNOTE-086 trial, which evaluated the safety and clinical activity of pembrolizumab monotherapy in mTNBC. The main cohort of the study was cohort A, which comprised women with previously treated mTNBC regardless of tumor PD-L1 expression.

Along with presenting the data from the 170 women in cohort A of KEYNOTE-086, Dr Adams shared preliminary results from cohort B, which enrolled women with previously untreated mTNBC with tumor PD-L1 expression.

Cohort A included women with mTNBC who had received at least 1 previous line of chemotherapy for metastatic disease and had documented disease progression. Prior treatment must have included an anthracycline and a taxane in the neoadjuvant, adjuvant, or metastatic setting.

Pembrolizumab was administered at 200 mg intravenously every 3 weeks for up to 2 years or until disease progression or intolerable toxicity. Tumor imaging was scheduled every 9 weeks for the first year and then every 12 weeks thereafter. Women with progressive disease who remained clinically stable could continue pembrolizumab until progressive disease was confirmed at the next evaluation. PD-L1 positivity was defined as at least 1% of tumor cells being PD-L1–positive. Of the 170 women in cohort A, 61.8% were PD-L1–positive, 37.6% were PD-L1–negative, and PD-L1 status was unknown in 0.6%.

After a median follow-up of 10.9 months, 9 women remained on treatment. The most common reason for discontinuation was disease progression (63.5% had radiologic progression and 24.7% had clinical progression).

The median age of women in cohort A was 53.5 years, 82.4% of women were postmenopausal, and 47.1% had an Eastern Cooperative Oncology Group performance status of 1. Adverse prognostic factors included an elevated lactate dehydrogenase (LDH) level in 51% of women, visceral metastases in 74.1%, and receipt of ≥3 prior lines of therapy in 43.5%. 

The median time on therapy was 56.5 days, and the median number of doses was 3. Based on RECIST v1.1 criteria, the ORR was 4.7% and the disease control rate was 7.6%. The best overall response was a complete response in 1 (0.6%) patient, partial responses in 7 (4.1%), and stable disease in 35 (20.6%). Progressive disease as a best response was recorded in 103 (60.6%) patients.

“Interestingly, there was no difference in response rate for PD-L1–positive and PD-L1–negative cohorts, although there was a slightly higher number with durable stable disease in the PD-L1–positive patients,” noted Dr Adams. The ORR was 4.8% in PD-L1–positive patients and 4.7% in PD-L1–negative patients. Twenty-seven percent of patients had a decrease in target lesion size from baseline. 

“As expected…women who had increased LDH, higher numbers of metastatic sites, and visceral involvement had numerically lower response rates,” she said.

The median time to response was 3.0 months, although responses occurred as late as 8 months after start of therapy. The median duration of response was 6.0 months, with the longest duration being 10.3 months (ongoing at the time of data analysis).

The median progression-free survival (PFS) was 2 months, with no apparent difference between PD-L1–positive and PD-L1–negative patients. The median OS was 8.9 months, again with no apparent difference based on PD-L1 status. The 6-month PFS and OS rates were 12% and 69%, respectively.

All patients with complete or partial responses were still alive at the time of data analysis. Six of 35 patients with stable disease had died at the time of data analysis. For those 2 cohorts, the median survival has not been reached. Median OS was 7.1 months for patients with progression as a best response.

Overall, 60% of patients had at least 1 all-grade treatment-related adverse event (TRAE); 12.4% of patients experienced grade 3/4 TRAEs, none of which were fatal. The most common all-grade adverse events were fatigue (20.6%) and nausea (10.6%). There were no deaths related to TRAEs.

Approximately 18.8% of patients had at least 1 immune-mediated adverse event of any grade, only 1.2% of which were grade 3/4. The most common all-grade immune-mediated adverse events were hypothyroidism (11.2%), hyperthyroidism (4.7%), and pneumonitis (3.5%). 

Cohort B includes 80 women with previously untreated PD-L1–positive mTNBC; response data from 52 of these women was also presented at ASCO 2017. The ORR in this cohort was 23.1%. In addition, 50% of the women had a decrease in targeted lesion size.

“The results of ongoing trials of pembrolizumab as monotherapy and combination therapies will further define the role of PD-1 blockade in TNBC,” Dr Adams concluded.


1. Adams S, Schmid P, Rugo HS, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol. 2017;35(suppl):Abstract 1008.
2. Den Brok WD, Speers CH, Gondara L, et al. Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed. Breast Cancer Res Treat. 2017;161:549-556.
3. Li X, Yang J, Peng L, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2016;161:279-287.
4. Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34:2460-2467.

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Last modified: August 22, 2017