Cancer Treatment Today

Preliminary results from the first immune therapy clinical trials suggested that some breast cancers are indeed responsive to immunotherapy with checkpoint blockade. The use of PD-1/PD-L1 inhibitors yielded response rates of 19% in 2 studies of women with heavily pretreated, PD-L1positive, triple-negative breast cancer.n a small study that was presented at the 2015 SABCS by Sylvia Adams,16 the PD-L1 inhibitor atezolizumab (Tecentriq, Roche) in combination with nab-paclitaxel (Abraxane, Celgene) showed impressive responses in triple-negative breast cancer. The response with the combination was nearly 70% in the first-line setting and approximately 25% to 30% in the second-line and third-line settings.Triple-negative breast cancers appear to be more likely than hormone-sensitive tumors to be associated with immune elements such as TILs, indicating an inherent interaction with the immune system. This inherent immune sensitivity may reflect, in part, the higher mutational load in this subtype and the associated increase in novel antigens for immune presentation. Given the reported response rates of 19% with PD-1/PD-L1targeted antibodies in women with heavily pretreated triple-negative breast cancer, much of the research has focused on this subtype.

At the 2015 SABCS, Hope Rugo presented the results of KEYNOTE-028, a phase 1b study of pembrolizumab alone in 25 women with ER-positive, HER2-negative, PD-L1 overexpressing advanced breast cancer who previously had received chemotherapy.

Triple-negative breast cancer (TNBC) is a clinically heterogeneous and molecularly diverse disease. At present, chemotherapy is the standard treatment for early-stage and metastatic TNBC. The paucity of actionable targets, lack of targeted therapies, and relatively poor prognosis of patients with TNBC have created ample opportunity to evaluate novel treatment approaches. CHeckpoint inhibitors are being studied.

At the 2015 SABCS, Hope Rugo presented the results of KEYNOTE-028, a phase 1b study of pembrolizumab alone in 25 women with ER-positive, HER2-negative, PD-L1 overexpressing advanced breast cancer who previously had received chemotherapy. Nivolumab and atezolizumab have also been studied. Early data from a phase I study suggest that the PD-L1 inhibitor atezolizumab (Tecentriq) can extend the lives of a subset of women who respond to this checkpoint inhibitor.

In summary, some intriguing trials have shown responses, more so in triple negative then hormone positive cases, and much more study needs to be done before it can be considered medically necessary.

Isha Dua, Immunotherapy for Triple-Negative Breast Cancer: A Focus on Immune Checkpoint Inhibitors. AJHO 2017: 13(4)L 20-27

Schmid P, Cruz C, Braiteh FS, et al: Atezolizumab in metastatic TNBC: Long-term clinical outcomes and biomarker analysis. 2017 AACR Annual Meeting. Abstract 298

Emens LA, Braiteh FS, Cassier P, et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC). In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; April 18-22, 2015; Philadelphia, PA. Abstract 2859.

Nanda R, Chow LQ, Dees EC, et al. A phase IB study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Presented at: 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. Abstract S1-09.

1Adams S, Diamond J, Hamilton E, et al. Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer. Presented at: 2015 San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract P2-11-06.

Rugo HS, Delord J-P, Im S-A, et al. Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. Presented at: 2015 San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract S5-07.

Dirix LY, Takacs I, Nikolinakos P, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase Ib JAVELIN solid tumor trial. Presented at: 2015 San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract S1-04.