New SITC Guidelines Provide First Recommendations for Immunotherapy in TNBC

Following the integration of immunotherapy into the treatment paradigm of triple-negative breast cancer (TNBC), a multidisciplinary panel of experts, brought together by the Society for Immunotherapy of Cancer (SITC), published the first clinical practice guidelines focused on navigating clinical decisions with immunotherapy in breast cancer, according to a publication in the Journal for ImmunoTherapy of Cancer.¹

“It’s an exciting time for immunotherapy in breast cancer,” said lead author Leisha A. Emens, MD, PhD, a professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, in a press release.² “This new guideline will help clinicians navigate the nuances of a dynamic and rapidly evolving field to offer their patients the benefits immunotherapy may provide.”

The panel concluded that for patients with locally advanced or metastatic TNBC with a disease-free interval of at least 12 months and PD-L1 immune cell (IC)–positive tumors by an IC score of at least 1 by SP142 assay analysis, atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) is recommended as a frontline immunotherapeutic option. For similar patients whose PD-L1 positivity was confirmed by a combined positive score (CPS) of at least 10 by the 22C3 assay, pembrolizumab (Keytruda) plus nab-paclitaxel, paclitaxel, or carboplatin plus gemcitabine is recommended as a frontline immunotherapeutic option.

Additionally, all patients with metastatic TNBC should be considered for clinical trial enrollment, have tumor tissue testing for PD-L1 by an FDA-approved assay for breast cancer, and undergo comprehensive genomic profiling, including tumor mutational burden and microsatellite instability testing.

“Immunotherapy is now offering some patients with breast cancer clinically meaningful benefit in early-stage and advanced disease,” said senior author Jennifer Litton, MD, a faculty member at The University of Texas Graduate School of Biomedical Sciences and vice president of Clinical Research in the Department of the Chief Scientific Office at The University of Texas MD Anderson Cancer Center.2 “It is important for clinicians and patients to understand that immunotherapy is very different from traditional breast cancer treatments, and this new guideline offers the expert guidance needed to safely consider these treatments.”

Historically, immunotherapy was not considered an effective treatment in breast cancer. However, checkpoint inhibitors in combination with chemotherapy have extended progression-free and overall survival compared with chemotherapy alone for patients with metastatic TNBC.

Despite this advancement, questions regarding the optimization of chemotherapy backbones for immunotherapy and biomarker-based patient selection remain. Additionally, further research is needed regarding the utilization of immunotherapy in earlier lines of treatment or for patients with other histological subtypes of breast cancer beyond TNBC.

Recent FDA approvals of checkpoint inhibitors in TNBC have shed light on an unmet need for evidence- and consensus-based guidelines regarding the utility of these agents in clinical practice. As such, a multidisciplinary panel of experts were brought together to inform such guidelines and answer relevant questions regarding recommended therapies, emerging agents, diagnostics and biomarkers, monitoring response to treatment, special patient populations, toxicity management, and quality of life (QOL).

“The recommendations within this guideline are not intended to supplant sound clinical judgment, but rather to provide clinicians with the most current thinking on how experts integrate immunotherapy into the treatment of patients with breast cancer,” Emens and coauthors wrote.¹

The panel modeled the Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines to develop the guidelines and all conflicts of interest were reported. The recommendations were based on previously published literature and clinical experience and were agreed upon with open communication and scientific debate, clinical questionaries, and formal voting.

Other key recommendations drawn by the panel state that all patients with stage II or III TNBC could be considered for neoadjuvant pembrolizumab or atezolizumab irrespective of PD-L1 status based on improved pathologic complete response rates vs chemotherapy alone. Moreover, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab should be considered a standard of care for patients with high-risk, early-stage disease.

Additionally, until harmonization of PD-L1 testing, patients with TNBC who are being considered for treatment with atezolizumab plus nab-paclitaxel should undergo tumor tissue testing with the SP142 assay, whereas patients who are being considered for pembrolizumab plus chemotherapy should undergo testing with the 22C3 assay. Patients should be scored with the IC system and CPS system, respectively.

Notably, the panel did not recommend PD-L1 testing for patients with early-stage disease currently.

Regarding toxicity management, the risk-benefit ratio of immunotherapy should be carefully considered for patients with comorbidities, active autoimmune diseases requiring immunosuppression, or those who have experienced toxicities with prior therapies. Moreover, patients should be monitored for at least 12 months following discontinuation of treatment to assess for immune-related adverse effects.

Finally, regarding QOL, patients, caregivers, and family members should be educated on the differences between immunotherapy and chemotherapy, as well as the potential for immune-related adverse effects and the importance of early toxicity recognition and management.

References

1. Emens LA, Adams S, Cimino-Mathews A, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer. J ImmunoTher Cancer. 2021;9(8):e002597. doi:10.1136/jitc-2021-002597
2. Society for Immunotherapy of Cancer publishes clinical practice guideline on immunotherapy for the treatment of breast cancer. News release. The Society for Immunotherapy of Cancer. August 18, 2021. Accessed August 20, 2021. https://prn.to/3z1eCEC