Immuno-Oncology Resource Center
Immuno-Oncology Resource Center
December 05, 2019
2 min read

Pembrolizumab plus radiotherapy safe, active in metastatic triple-negative breast cancer

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Alice Y. Ho, MD
Alice Y. Ho

Pembrolizumab plus radiotherapy appeared safe and demonstrated encouraging clinical activity among a small cohort of women with poor-prognosis, metastatic triple-negative breast cancer, according to results of a phase 2 trial published in Cancer.

Responses to the combination appeared more likely when administered earlier in the treatment course and in PD-L1-positive tumors, researchers found.

“Although radiation is a sophisticated and practical local therapy for women with metastatic triple-negative breast cancer, we felt that its full potential as an immune-modulating treatment has been slow to be accepted in breast cancer,” Alice Y. Ho, MD, director of breast service in the department of radiation oncology at Massachusetts General Hospital, told Healio. “By combining radiation with immunotherapy, our goal was to unleash its potential and improve upon not just local, but also distant [abscopal] outcomes for patients.”

The single-arm, Simon 2-stage, phase 2 trial by Ho and colleagues included 17 women (median age, 52 years; range, 37-73; 65% white) with metastatic triple-negative breast cancer. Five of the women had previous ER-positive breast cancer that transformed into metastatic triple-negative breast cancer, and 14 had received neoadjuvant systemic breast cancer therapy.

Women were unselected for PD-L1 expression and assigned a radiotherapy dose of 3,000 cGy administered in five daily fractions. They received pembrolizumab (Keytruda, Merck) at a dose of 200 mg IV within 3 days of the first radiotherapy fraction followed by every 3 weeks until disease progression or unacceptable toxicity.

Median duration of treatment from the initiation of radiotherapy was 61 days, and women received a median four (range, 1-20) pembrolizumab doses.

Overall response rate at week 13 among women with unirradiated lesions, measured per RECIST version 1.1 criteria, served as the study’s primary endpoint. Secondary endpoints included safety and PFS. Exploratory objectives included identification of biomarkers predictive of ORR and PFS.

Median follow-up was 34.5 weeks (range, 2.1-108.3).

Results showed an ORR of 17.6% (95% CI, 4.7-44.2), with three complete responses, one woman with stable disease and 13 women with progressive disease.

Eight women died of disease progression before week 13. Among the nine women assessed per RECIST version 1.1 criteria at week 13, three had complete responses with complete reduction in tumor volume outside of the irradiated portal. Complete responses among the three women remained durable for 18 weeks, 20 weeks and 108 weeks. Although these women were found to be PD-L1 positive at baseline, the researchers did not observe a significant correlation between ORR and PD-L1 expression at baseline or at 7 weeks.


Median PFS was 2.6 months (95% CI, 1.8-5.2), with a 6-month PFS rate of 18%.

Median OS was 7.6 months (95% CI, 2.3-not reached), with a 6-month OS rate of 53% and 1-year OS rate of 41%.

The most common grade 1 to grade 2 adverse event, dermatitis, occurred among 29% of women. Grade 3 adverse events associated with pembrolizumab included fatigue, lymphopenia and infection. Researchers observed no grade 4 adverse events or deaths related to treatment.

“For our subsequent trials, we are examining immunotherapy plus radiation combinations in the preoperative setting, for both triple-negative and high-risk, hormone receptor-positive breast cancers,” Ho told Healio. “We are also conducting more studies in the setting of metastatic triple-negative breast cancer that build upon the immunotherapy-plus-radiation backbone by adding novel but rational combinations, such as PARP inhibitors, in women with triple-negative breast cancer who progress on chemotherapy plus immunotherapy alone.” – by Jennifer Southall

For more information:

Alice Ho, MD, can be reached at Massachusetts General Hospital, 55 Fruit St., Boston MA 02114; email:

Disclosures: Merck funded the study. Ho reports grants from Merck for work performed as part of the current study. Please see the study for all other authors’ relevant financial disclosures.